KY-19382 Guide: Everything you need to know for Longitudinal Bone Growth / Cranio-facial Growth / Hair Regeneration / EYE colour change / Sources

[scuderia]

Not much to read

Only like half my ap language essay mb

 

[Jordan Barrett]

Nigga

Cest toi le negre

 

[jnxy]

Only like half my ap language essay mb

i put way to much effort into ts

I barely got like 1/10th of the thread done

 

[scuderia]

Not much to read

Oh and also make a guide on eyes and facial growth with ky19

Or a mini guide about it not much is needed to be said

 

[jnxy]

Cest toi le negre

Je nique ta soeur

 

[jnxy]

Oh and also make a guide on eyes and facial growth with ky19

Or a mini guide about it not much is needed to be said

it's about changing eye colour and lightening up the iris

 

[scuderia]

it's about changing eye colour and lightening up the iris

Ya ik

Are you on ky19 btw I saw your stack a couple weeks back in a thread but I don’t remember

 

[jnxy]

Ya ik

Are you on ky19 btw I saw your stack a couple weeks back in a thread but I don’t remember

not as of rn. I have powder laying around but too lazy to do anything with it. might just make oral capsules.

 

[scuderia]

not as of rn. I have powder laying around but too lazy to do anything with it. might just make oral capsules.

Oh I see

Im provably just gonna overpay for the pre made injectable version

Bt/nexora research sells it now

 

[jnxy]

Oh I see

Im provably just gonna overpay for the pre made injectable version

Nice.

Bt/nexora research sells it now

The fuck no they don't, also those niggers take years to reply

Bt got banned recently

 

[_Jason_]

Mirin Guide Brah

 

[jnxy]

Mirin Guide Brah

preesch

 

[scuderia]

The fuck no they don't, also those niggers take years to reply

Nexora doesn’t

Bt did get banned tho

 

[jnxy]

Nexora doesn’t

Bt did get banned tho

I paid once for smth and he dint even ship the order. This was like a month ago

 

[scuderia]

I paid once for smth and he dint even ship the order. This was like a month ago

Ask nexora about it

All US orders were sent to him to manage since bt only does international

 

[jnxy]

Ask nexora about it

All US orders were sent to him to manage since bt only does international

Im international lol

 

[scuderia]

Im international lol

Oh then it’s ova

 

[zennn]

Credits @Niebvll, got inspired by this thread in german. Make sure to rep and follow him: HERE

FUCK THIS THREAD I JUST WASTED MY TIME WALLAHI. GO DO SOMETHING BETTER WITH YOUR TIME OF DAY. THIS THREAD IS NOT COMPLETED IN THE SLIGHTEST

I COULD HAVE DONE ITS EFFECT ON
- FACIAL BONES
- HAIR
- EYE COLOUR (POTENTIALLY)

+ THE HEIGHT SECTION IS COMPLETELY HALF-ASSED ANYWAYS:

Preface:

It will happen that in some places, the spelled out Latinized form of Greek letters is used, while in others the actual Greek character appears. This is because I wrote out more common terms (e.g. beta-catenin), but sometimes, especially when individual terms were harder to remember or type, I simply copied and pasted them directly.

It may also happen that some passages appear twice because my note-taking app (One note, cagefuel ik) sometimes glitches.

It’s a longer thread my faggots, so I’d recommend putting on a playlist rather than listening to a single song. For example, this one, if you’re too lazy to make one yourself right now:

Spoiler: Disclaimer: DNR this

This material is intended for educational and informational purposes only. It is not intended to provide medical advice, diagnosis, treatment, or a substitute for consultation with a qualified healthcare professional.

The information presented may include experimental findings, emerging research, or simplified explanations and should not be interpreted as established clinical guidance. Some compounds, mechanisms, treatments, or applications discussed may be preclinical or have limited evidence in humans.

Always consult an appropriately qualified healthcare professional before making decisions regarding your health, medications, or treatment. Do not use any information in this material to self-diagnose, self-treat, or change prescribed treatment.

Playlist:

What even is KY-19382? ​

KY-19382, we will shorten it to KY, is a synthetic small molecule that activates the Wnt/β-catenin signaling pathway. Unlike compounds that inhibit Wnt signaling, KY-19382 actually increases Wnt activity. It does this through two main mechanisms: it disrupts the interaction between CXXC5 and Dishevelled (DVL) and inhibits GSK3β, both of which normally act to limit Wnt/β-catenin signaling.

CXXC5 is a negative regulator of the Wnt pathway. It binds to DVL and helps suppress downstream signaling. By interfering with this interaction, KY-19382 removes one of the pathway's main brakes. At the same time, inhibiting GSK3β reduces the degradation of betacatenin, allowing more of it to accumulate and enter the nucleus.

In simple terms:

KY-19382 → CXXC5–DVL inhibition + GSK3β inhibition → increased β-catenin → increased Wnt signaling (Image B)

View attachment 5667764

This is particularly interesting in the context of bone growth. In animal studies, KY-19382 increased activity in the growth plate and was associated with increased proliferation and hypertrophy of chondrocytes, as well as increased longitudinal bone growth of the tibia (more on this later duh).

KY-19382 has also been investigated in other contexts involving Wnt/β-catenin signaling, including hair regeneration and wound healing. Its effects in these areas have likewise been studied mainly in experimental models. (more on this later duh)

Basic Understanding of the Wnt/β-Catenin Signaling Pathway
​

Think of cells as following a command chain. Wnt is one of these signaling systems and is involved in growth, development, and tissue renewal. Among other things, Wnt signaling regulates cell division, cell differentiation (which is relevant for bone development and remodeling), and different stages of cell development.

Under normal conditions, β-catenin is constantly produced but is also continuously marked for degradation by a protein complex known as the destruction complex. One of its main components is GSK3β, which helps phosphorylate β-catenin and target it for degradation. When Wnt signaling is activated, this process is inhibited, allowing β-catenin to accumulate and eventually enter the cell nucleus.

This is where KY becomes relevant. KY inhibits GSK3β, which reduces the degradation of β-catenin and therefore allows more of it to accumulate. At the same time, KY-19382 interferes with the interaction between CXXC5 and Dishevelled (DVL). CXXC5 normally acts as a negative regulator of Wnt signaling, so disrupting this interaction removes another brake on the pathway.

The result is increased Wnt/β-catenin signaling, with more β-catenin available to enter the nucleus and influence gene expression. Among the genes and processes associated with this pathway are those involved in cell proliferation, differentiation, and bone formation, including factors such as RUNX2 and osteocalcin that are relevant to osteoblast differentiation and activity.

Most people here have probably heard of osteoblasts already. If not, I’ll add a short explanation of how bone formation works below.

Spoiler: "Bone Formation, cells and the growthplate"

HUGE CREDITS TO: @Niebvll basically stole everything from him bcs i CBA to write all this shit for you fags

I. Bone Formation​

Bones consist of living tissue made up of three main cell types: osteoblasts, osteocytes, and osteoclasts. All of these cells are embedded within an extracellular matrix, which consists of roughly 45% inorganic minerals (mainly calcium and phosphate compounds), around 30% organic components such as collagen, and water.

II. Relevant Bone Cells​

Osteoblasts are essentially the body's bone-building cells. They develop from mesenchymal stem cells and are found mainly on the surface of bones, particularly in areas where growth, remodeling, or repair is taking place.

Biochemically, osteoblasts are highly active protein producers. Their cytoplasm contains a large amount of rough endoplasmic reticulum because they constantly produce collagen and other matrix proteins. Most of the organic bone matrix consists of type I collagen, which gives bone much of its tensile strength. Other components include osteocalcin, osteopontin, bone sialoprotein, and various proteoglycans.

Once the osteoid, meaning the organic bone matrix, has been produced, osteoblasts release enzymes such as alkaline phosphatase. These promote the deposition of calcium and phosphate, allowing hydroxyapatite crystals to form and harden the bone.

Osteoblasts also help regulate bone remodeling by producing signaling molecules that influence osteoclasts. After completing their work, some osteoblasts die, while others either become osteocytes or remain on the bone surface as inactive cells.

Osteocytes are the most abundant type of bone cell, making up roughly 90–95% of all bone cells. They develop from osteoblasts that become completely embedded in the matrix they produced. They reside in tiny cavities called lacunae and are connected through an extensive network of small channels called canaliculi.

Through these cellular extensions, osteocytes exchange nutrients, ions, and signaling molecules. They act as mechanical sensors for the skeleton: when bone is subjected to mechanical loading, changes in the fluid flow through these channels are detected by the cells. In response, they release signaling molecules that regulate bone formation and resorption.

One particularly important protein is sclerostin, which inhibits osteoblast activity. Osteocytes also release RANKL, which promotes osteoclast formation, and FGF23, a hormone involved in phosphate metabolism and vitamin D regulation. In this way, osteocytes help coordinate bone remodeling and function as a central regulatory system within bone tissue.

Osteoclasts are large, multinucleated cells whose primary function is to break down bone. Unlike osteoblasts, they do not originate from mesenchymal stem cells. Instead, they develop from the hematopoietic lineage, with multiple precursor cells fusing together to form a large cell containing many nuclei.

At the bone surface, osteoclasts form a highly folded membrane structure known as the ruffled border. This area contains proton pumps and chloride channels that allow the cell to pump hydrochloric acid into the resorption compartment. The acid dissolves the mineral component of bone.

Osteoclasts then release enzymes such as cathepsin K and various matrix metalloproteinases, which break down collagen fibers and other organic components. The calcium and phosphate released during this process contribute to the continuous renewal of the skeleton. Without osteoclasts, old or damaged areas of bone could not be properly removed. A healthy skeleton therefore depends on a balance between osteoclast and osteoblast activity.

Osteoprogenitor cells are precursors to osteoblasts. They are found mainly in the periosteum (the outer membrane surrounding bone), the endosteum (the inner lining of bone), and the bone marrow.

They resemble fibroblasts and do not yet have the highly developed protein-producing machinery of mature osteoblasts. Their main function is to provide new osteoblasts when needed. During growth, fracture repair, or normal bone remodeling, they become activated and divide. They then gradually differentiate into mature osteoblasts.

This process is regulated by numerous growth factors and signaling pathways, including BMPs (Bone Morphogenetic Proteins), Wnt signaling, and various hormones. Osteoprogenitor cells therefore provide an important regenerative reserve and are essential for maintaining bone mass throughout life.

Bone-lining cells are inactive osteoblasts that are no longer actively producing matrix. They cover large areas of the bone surface as a thin layer. They help regulate the exchange of calcium and phosphate between bone and blood, protect the bone surface, and support the remodeling process.

When a particular area needs to be remodeled, these cells can release signals that help recruit osteoclasts and osteoblasts. Under certain conditions, they can also become active osteoblasts again.

Chondrocytes are the cells that make up cartilage. In the growth plates of long bones, they are responsible for longitudinal bone growth.

They produce a matrix containing type II collagen, aggrecan, chondroitin sulfate, keratan sulfate, and hyaluronic acid. This matrix binds large amounts of water and gives cartilage its ability to withstand compression.

Within the growth plate, chondrocytes pass through several stages: resting cells, proliferating cells, which divide rapidly, and hypertrophic cells, which become significantly larger. Hypertrophic chondrocytes produce type X collagen and contribute to calcification of the surrounding matrix.

Eventually, these cells often undergo cell death while blood vessels, osteoblasts, and osteoclasts enter the area and the cartilage is replaced by bone. This process, known as endochondral ossification, is responsible for longitudinal bone growth and contributes to the increase in bone volume.

Bone marrow stromal cells (BMSCs) are multipotent mesenchymal stem/stromal cells found in the bone marrow. They can give rise to several different tissue and cell types, including osteoblasts, chondrocytes, adipocytes, fibroblasts, and other mesenchymal cells.

Biochemically, they are characterized by their flexible gene expression, which allows them to respond to different signaling molecules and environmental conditions. Within the bone marrow, they also form an important part of the microenvironment that supports blood-forming stem cells.

They produce growth factors, cytokines, and components of the extracellular matrix and therefore contribute indirectly to blood formation and tissue maintenance.

III. Growth Plates​

The growth plate can broadly be divided into three main zones:

Resting Zone​

This is the uppermost layer of the growth plate, located directly at the end of the bone. The cells here are mostly inactive and divide only rarely. They act as a kind of reserve population of cartilage cells, slowly providing new cells for the layers below when needed.

Proliferative Zone​

This is the active “production zone.” The chondrocytes divide rapidly and arrange themselves into organized columns, similar to stacks of coins.

Each round of proliferation contributes to the overall expansion of the growth plate and therefore to longitudinal bone growth. This is one of the most active regions of the growth plate and plays a major role in determining how quickly a long bone grows.

Hypertrophic Zone​

In this zone, the cells stop dividing and instead begin to grow dramatically in size. Their enlargement contributes to further expansion of the growth plate.

At the same time, they modify the surrounding cartilage matrix and prepare the tissue for mineralization. Eventually, the hypertrophic chondrocytes undergo cell death, blood vessels and bone-forming cells enter the region, and the calcified cartilage is replaced by bone.

This represents the final stage of endochondral ossification, through which cartilage is progressively converted into mature bone.

That is about all you need to know.

KY-19382's Molecular Mechanism of Wnt/β-catenin Activation. (Mini Deep-Dive)​

1. CXXC5​

CXXC5 stands for CXXC-type zinc finger protein 5. It is a relatively small intracellular protein, best known for its role as a negative regulator of the Wnt/β-catenin pathway. The name comes from its characteristic CXXC zinc-finger domain, a structural motive involved in protein interactions.

What makes CXXC5 special is its interaction with Dishevelled (DVL). DVL is one of the important intracellular components of the Wnt pathway. When Wnt binds to the Frizzled/LRP5/6 receptor complex at the cell surface, DVL is recruited and helps pass the signal further into the cell. From there, the signaling cascade eventually leads to stabilization of β-catenin and activation of Wnt-responsive genes.

CXXC5 puts a brake on this process. It can bind to DVL and interfere with its ability to efficiently transmit the Wnt signal. So, rather than blocking Wnt before it reaches the cell, CXXC5 acts further downstream (like many other compounds), at the level of the intracellular signaling machinery.

There is also a feedback mechanism involved. Activation of Wnt signaling can increase the expression of CXXC5 itself. Simply put nigger, the pathway contains its own mechanism for putting the brakes on after being activated. More Wnt signaling can lead to more CXXC5, which then interacts with DVL and helps limit further signaling.

It is part of the system that determines how strong and how long the Wnt signal remains active.

2. GSK3β​

Now we get to the second part of KY19382's mechanism: GSK3β, or glycogen synthase kinase 3 beta.

GSK3β is a kinase, meaning its job is to add phosphate groups to other proteins (phosphorylation wallahi most of you niggers must know this). One of its most important jobs is controlling the amount of β-catenin inside the cell.

Under normal conditions, β-catenin is constantly being produced, but it doesn't simply sit around and accumulate. When Wnt signaling is inactive, β-catenin is captured by the so-called destruction complex, where it is phosphorylated by CK1 and GSK3β. These phosphorylation marks essentially label β-catenin for destruction. It is then ubiquitinated (I just learned this term when doing research ) and sent to the proteasome, where it gets broken down.

So, very simplified:

GSK3β active → β-catenin gets phosphorylated → β-catenin gets degraded → little β-catenin reaches the nucleus

This is one of the main reasons the cell can keep Wnt signaling switched off when there is no Wnt signal telling it to do otherwise.

When Wnt signaling is activated, however, this destruction process is inhibited. GSK3β can no longer efficiently phosphorylate β-catenin, so β-catenin becomes more stable, accumulates in the cytoplasm, and can eventually enter the nucleus. There it interacts with TCF/LEF transcription factors and helps activate Wnt-responsive genes.

And this is where KY-19382 comes in for a second time.

KY-19382 inhibits GSK3β, meaning β-catenin is no longer phosphorylated and degraded as efficiently. The result is increased β-catenin stability and accumulation, which pushes the pathway toward stronger Wnt/β-catenin signaling.

So we now have two separate effects of KY-19382:

CXXC5–DVL inhibition
→ removes a negative regulator of Wnt signal transmission

GSK3β inhibition
→ reduces β-catenin degradation

↑ β-catenin → ↑ nuclear β-catenin → ↑ Wnt target gene activity

This is what sets KY-19382 apart from other indirubin derivatives or Wnt/β-catenin compounds: it targets the pathway at two separate points. Fascinating right faggots? right? Yeah fuck all of you, especially the nigha @ragingmanlet.

NOTE: Everything I've covered in this molecular section is a very broad and simplified overview of a much more complicated pathway

For example, you could go much deeper into almost every step we've discussed:

• The different Frizzled receptors and LRP5/6 co-receptors and how individual Wnt ligands interact with them
• The different domains of DVL and exactly how DVL changes its conformation and signaling behavior
• The CXXC5–DVL interaction, including the C-terminal region of CXXC5 and the PDZ domain of DVL
• How KY-19382 interacts with this system at the molecular level and what is known versus what has only been proposed through structural modeling
• The individual phosphorylation steps carried out by CK1 and GSK3β
• The roles of Axin, APC, β-TrCP, and the other components of the β-catenin destruction complex
• How β-catenin moves between the cytoplasm and nucleus
• The interaction between β-catenin and TCF/LEF transcription factors
• The many different genes and transcriptional programs that can be influenced downstream
• The feedback mechanisms that regulate Wnt signaling, including proteins such as CXXC5, SFRPs, DKKs, and others
• How ubiquitination and proteasomal degradation regulate the abundance of signaling proteins such as CXXC5 and β-catenin

But WE yes WE as Looksmaxxers dgaf about this science nerd thingy duh

We only care about the JUICY Stuff...

KY-19382 for longitudinal bone growth (Height nigga)​

So how could increasing Wnt/β-catenin signaling actually affect longitudinal bone growth?

These cells continuously pass through different stages: they proliferate, differentiate, become hypertrophic, and are eventually replaced by bone. The rate at which this process happens has a direct effect on how quickly the bone elongates.

Wnt/β-catenin signaling is involved throughout this process. When Wnt signaling is increased, β-catenin becomes more stable, accumulates in the cell, and enters the nucleus. There it interacts with TCF/LEF transcription factors and changes the expression of Wnt-responsive genes. In growth-plate chondrocytes, this can affect both proliferation and differentiation.

In the proliferative zone, increased Wnt/β-catenin activity can support the production of new chondrocytes. More rounds of cell division mean more cells are available to move through the growth plate and eventually enter hypertrophic differentiation. The important point is that longitudinal growth depends not only on how large individual chondrocytes become, but also on how many cells are being produced and how quickly they progress through the growth plate.

Wnt signaling also affects the transition toward hypertrophy. β-catenin activity is linked to factors such as RUNX2 and other genes involved in chondrocyte maturation. As chondrocytes become hypertrophic, they increase in volume and produce a different set of extracellular-matrix proteins, including collagen X. The cartilage is then progressively remodeled and replaced by bone on the metaphyseal side of the growth plate.

So increasing Wnt/β-catenin activity can affect several parts of the same process:

Wnt/β-catenin ↑ → chondrocyte proliferation ↑ → more chondrocytes enter the growth-plate program → differentiation and hypertrophy ↑ → more cartilage is produced for replacement by bone → longitudinal growth can increase

The growth plate does not stay active forever (fusion). During puberty, its activity gradually declines and the plate becomes senescent. One of the proteins involved in this process is CXXC5.

CXXC5 acts as a negative regulator of Wnt/β-catenin signaling by interacting with Dishevelled (DVL). As CXXC5 increases, this inhibitory effect becomes stronger and Wnt signaling is reduced. That means less β-catenin reaches the nucleus and the expression of genes associated with active chondrocyte behavior decreases.

Estrogen signaling increases during puberty, and estrogen can increase CXXC5 expression in growth-plate chondrocytes. As CXXC5 rises, Wnt/β-catenin signaling is suppressed and the growth plate gradually becomes less active.

In simplified form:

Estrogen ↑ → CXXC5 ↑ → Wnt/β-catenin ↓ → growth-plate activity ↓ → senescence of the resting zone (fusion)

Over time, this contributes to the normal shutdown of longitudinal bone growth. In humans, the process eventually ends with epiphyseal fusion, when the growth plate is replaced by bone and there is no longer an active cartilage plate capable of producing further longitudinal growth.

If CXXC5 helps suppress Wnt signaling as the growth plate ages, then interfering with CXXC5 could have the opposite effect: maintaining β-catenin signaling, keeping chondrocytes active for longer, and potentially delaying some of the changes associated with growth-plate senescence. (Translation for Iqlets: Keep the Plates open for longer and increase Velocity)

TLR: Estrogenic activity (binding ERA AF2) increases CXXC5, which leads to decreased growth plate activity and this ends and "depletes/kills" the resting zone and replaces it with bone (luncae)

Now, Does KY have any evidence or is this just speculation?

Actually, we do have evidence and let me tell you my friend, it's looking bright.

“CXXC5 mediates growth plate senescence and is a target for enhancement of longitudinal bone growth” (PMID30971423)

Note: I tried a type of a story-time telling. Inspo @Tesarossa
​

So what actually happend?​

Instead of starting with KY-19382, our dear researchers looked at growth plates at different stages of development and compared the expression of CXXC5 with markers of Wnt/β-catenin activity and chondrogenesis.

They found that as the animals progressed through puberty, CXXC5 expression gradually increased (likely due to increased estrogen-signaling) . At the same time, β-catenin and several markers associated with active chondrocytes decreased.

So there is a pretty clear pattern:

pubertal progression → CXXC5 ↑ → Wnt/β-catenin activity ↓

But this still didn't tell them whether CXXC5 was actually involved in causing the decline, or whether it was simply changing alongside it.

So they went one step further.

The researchers then asked what happens if CXXC5 is removed altogether. They used mice in which the Cxxc5 gene had been knocked out and compared them with normal mice.

And the difference was noticeable.

As the normal mice aged, their growth plates showed the usual signs of senescence: fewer active chondrocytes, reduced proliferation and reduced Wnt/β-catenin activity. The Cxxc5-knockout mice retained more of this activity at later ages.

They also had longer tibia.

The researchers then asked whether they needed to remove CXXC5 completely to get this effect.

They already knew that CXXC5 interacts with Dishevelled (DVL) and suppresses Wnt signaling through this interaction. So instead of deleting the entire gene, they used a blocking peptide, PTD-DBMP, to interfere specifically with the CXXC5–DVL interaction.

Again, blocking this interaction increased β-catenin signaling and increased the number of proliferating and hypertrophic chondrocytes in the growth plate.

At this point, the idea was becoming much more interesting:

CXXC5 ↑ → Wnt signaling ↓ → growth-plate activity ↓

while interfering with CXXC5 gave them the opposite direction.

But a peptide or a complete gene knockout isn't exactly the same thing as having a small molecule that could be used experimentally.

So the researchers went looking for one.

They screened 2,280 compounds for molecules capable of interfering with the CXXC5–DVL interaction. This eventually led them to indirubin-based compounds and, from there, to the compound we're interested in:

KY-19382. (our goat)

But finding a compound that works in a screening assay isn't enough. They needed to test whether KY actually affected both of the targets they were interested in.

First, they tested the CXXC5DVL interaction directly. KY-19382 inhibited this interaction with an IC₅₀ of approximately 19 nM.

They then tested GSK3β kinase activity separately. KY-19382 inhibited GSK3β with an IC₅₀ of approximately 10 nM.

The next question was whether those two effects actually translated into increased Wnt/β-catenin signaling inside cells.

For that, they used the TOPFlash reporter assay, which is commonly used to measure β-catenin/TCF-dependent transcription. Increasing concentrations of KY-19382 increased TOPFlash activity, showing that the compound was activating Wnt/β-catenin signaling in the cells.

They then went a step further and looked at what was happening to the proteins themselves.

In ATDC5 chondrocytes, KY-19382 increased β-catenin while reducing the active forms of GSK3α/β. They also performed an immunoprecipitation experiment to directly examine the CXXC5–DVL interaction. After KY treatment, the interaction was reduced.

And finally, they looked at where the β-catenin was going.

After treatment with KY-19382, substantially more β-catenin was detected in the nucleus of the chondrocytes.

So what happens when they put KY-19382 into mice?​

Now that they had shown that KY-19382 could activate Wnt/β-catenin signaling in cells, the researchers wanted to see whether the same thing happened in an actual growth plate.

They started with 7-week-old mice, which are already approaching the later stages of pubertal growth.

The mice received 0.1 mg/kg KY-19382 every day for 2 weeks. After treatment, the researchers examined the tibial growth plates and compared them with vehicle-treated controls.

The growth plate was larger in the KY-treated animals.

But they didn't just measure its overall size. They also looked at what the cells inside the growth plate were actually doing.

They used BrdU staining to identify proliferating cells and RUNX2 as a marker associated with hypertrophic differentiation. Both were increased after KY-19382 treatment.

They also looked at β-catenin itself.

And this was especially clear: nuclear β-catenin was strongly increased in the growth-plate chondrocytes.

So the change in growth-plate size came together with molecular and cellular changes that fit with increased Wnt/β-catenin activity.

They then repeated the experiment in 3-week-old mice, which are still undergoing rapid growth.

Again, the animals received 0.1 mg/kg KY-19382 daily for 2 weeks.

This time, the total growth-plate height increased, as did the heights of its individual zones. The number of BrdU-positive cells also increased, showing that more chondrocytes were actively proliferating.

But there was another question they needed to rule out.

If the hypertrophic zone becomes larger, that doesn't automatically mean the growth plate is producing more cells. It could also happen if the cartilage is simply being removed more slowly at the cartilage-to-bone interface.

So they looked at TRAP-positive foci, which mark osteoclast activity at this interface.

In the young mice, there was no significant difference in TRAP-positive foci between the KY-treated and control groups.

That makes a simple explanation based on reduced cartilage resorption less convincing.

Interestingly, the result was different in the older 7-week-old animals: KY-19382 increased TRAP-positive foci. The researchers interpreted this as evidence that KY was not merely accumulating cartilage in the growth plate, but was actually promoting the overall maturation process.

So by this point, the picture was becoming much more concrete.

And then they measured the bone itself​

The short-term experiments had shown that KY-19382 could make the growth plate more active. But the researchers wanted to know whether that effect was large enough to change the final length of the bone.

So they designed a much longer experiment.

They started with 3-week-old male C57BL/6 mice and treated them with 0.1 mg/kg KY-19382 by intraperitoneal injection every day for 10 weeks. The control animals received the vehicle instead.

This means the mice were followed from roughly 3 weeks of age to 13 weeks of age, covering a substantial part of the period in which their longitudinal growth normally slows down.

After the 10 weeks, the researchers took radiographs and measured the tibiae.

And this time, the result wasn't just a change in a staining pattern or in the appearance of the growth plate.

The KY-19382-treated mice had significantly longer tibiae than the vehicle-treated mice.

The reported difference was statistically significant, with P < 0.0005.

That gives the study an important progression:

There is, however, an important distinction here.

This experiment demonstrates the effect of KY-19382 as a compound. It does not prove that the increase in tibial length came exclusively from CXXC5 inhibition, because KY-19382 also inhibits GSK3β. (We dgaf about this tho)

The earlier Cxxc5 knockout experiments are therefore important for the CXXC5-specific part of the story, while the KY experiments show what happens when both of these mechanisms are affected by the compound.

The researchers also looked for obvious signs of toxicity during the long-term treatment. They reported no significant difference in body weight and found no histological abnormalities in the examined articular cartilage or liver.

That is reassuring within the limits of this particular experiment, but it doesn't turn KY-19382 into a proven safe compound. These were still preclinical mouse experiments, using a compound that has not been established as a human treatment.

At this point, the researchers had shown something quite substantial in mice:

CXXC5 is associated with the loss of growth-plate activity during maturation, removing or interfering with CXXC5 preserves Wnt/β-catenin signaling, and pharmacological activation with KY-19382 was associated with increased growth-plate activity and, after prolonged treatment, increased tibial length.

But the researchers still had another piece of the puzzle to address:

Why does CXXC5 increase during puberty in the first place?

That brings us back to estrogen.

The researchers then asked whether estrogen could be the signal driving this increase in CXXC5 during puberty.

They treated human chondrocytes with 17β-estradiol (E2) and found that CXXC5 expression increased after estrogen exposure, while β-catenin levels decreased. So the relationship seen during puberty could also be reproduced experimentally: more estrogen, more CXXC5, less active Wnt/β-catenin signaling.

They then looked at what this actually meant for the growth plate. When tibial growth plate cultures were treated with E2, longitudinal growth was reduced, together with reductions in the proliferative and hypertrophic zones. In other words, estrogen was not simply changing CXXC5 expression in isolation. It was associated with the structural changes that accompany growth plate senescence.

The strongest evidence came from the Cxxc5 knockout mice. When estrogen was given to normal mice, the growth plate developed the expected senescent changes. But when the same experiment was performed in mice lacking Cxxc5, most of that estrogen-induced phenotype was lost.

That places CXXC5 downstream of estrogen in this model. The study therefore supports a mechanism in which the rise in estrogen during puberty increases CXXC5, CXXC5 suppresses Wnt/β-catenin signaling, and the resulting reduction in chondrocyte activity contributes to growth plate senescence.

And that gives the whole study a much more complete chain:

Instead of simply adding a growth-promoting signal from outside, the compound interferes with one of the mechanisms that normally suppresses Wnt signaling. It blocks the CXXC5–DVL interaction while also inhibiting GSK3β, giving β-catenin two routes to remain active.

So the paper is essentially connecting two levels of the problem: the developmental signal that increases CXXC5 during puberty, and the molecular machinery through which CXXC5 reduces Wnt activity in the growth plate. The experiments with KY-19382 then ask whether interfering with that machinery is enough to preserve growth plate activity and extend longitudinal bone growth.

In the mouse experiments, the answer was yes: the growth plate remained more active, chondrocyte proliferation and maturation were increased, and prolonged treatment produced measurable increases in tibial length.

So what does the mouse dose mean in humans?​

The researchers used KY-19382 at 0.1 mg/kg once daily in the mouse experiments. The short-term studies lasted 2 weeks, while the long-term experiment treated the mice daily for 10 weeks, from 3 to 13 weeks of age.

A common preclinical approach is to use body-surface-area scaling, which gives a rough human-equivalent dose (HED).

For mice, the standard Km factor is 3, compared with 37 for an adult human:

HED = animal dose × (mouse Km / human Km)

So for the dose used in this study:

0.1 mg/kg × 3/37 ≈ 0.0081 mg/kg

That corresponds to roughly:

• 60 kg human → 0.49 mg/day
• 70 kg human → 0.57 mg/day
• 80 kg human → 0.65 mg/day

So, purely as a body-surface-area conversion, the 0.1 mg/kg mouse dose corresponds to about 0.5–0.65 mg in a 60–80 kg adult human.

Simple math duh .

Administration

I honestly CBA to make a guide on administration and lowkey want to go to sleep.

You have 2 choices:

1. Oral

Guide: Geometrically dilute the powder and put it in capsules (duh)
Note: You will need to account for a lower Bioavailibility

2. SubQ

Guide: Watch my friends video on TT on how to make a DIY solution:


Sources and Price:

Cost per Gram: Usually varies between 200$-600$

look on sites such as Echemi or Lookchem for good vendors.

If you can't find a source DM me.

I won't even correct my grammar I CBA Fuck all of you,

YES I USED AI TO FORMAT EVERYTHING NIGGER, IT'S 2026. Why would I not?



​

Oheiiiii holy shit holy Long thread holy botb

Holy bump

 

[Gudlifer]

• 60 kg human → 0.49 mg/day
• 70 kg human → 0.57 mg/day
• 80 kg human → 0.65 mg/day

bro doesnt know im doing 5mg IV ED at 50kg till I get multiple types of melanoma while all my grandparents and (dead) uncles/aunts died from cancer

 

[jnxy]

Oheiiiii holy shit holy Long thread holy botb

Holy bump

BOTB

Got too lazy to finish thread at the end

 

[jnxy]

bro doesnt know im doing 5mg IV ED at 50kg till I get multiple types of melanoma while all my grandparents and (dead) uncles/aunts died from cancer

This actually made me cage

Inb4 death

 

[Gudlifer]

This actually made me cage

Inb4 death

nah but im only gonna do 2mg IV, im chilling
and not ALL my grandparents and aunts died from cancer only half

 

[jnxy]

nah but im only gonna do 2mg IV, im chilling
and not ALL my grandparents and aunts died from cancer only half

Huff. Got me stressed out there for a sec. I’m relieved now

 

[sasha108]

Credits @Niebvll, got inspired by this thread in german. Make sure to rep and follow him: HERE

FUCK THIS THREAD I JUST WASTED MY TIME WALLAHI. GO DO SOMETHING BETTER WITH YOUR TIME OF DAY. THIS THREAD IS NOT COMPLETED IN THE SLIGHTEST

I COULD HAVE DONE ITS EFFECT ON
- FACIAL BONES
- HAIR
- EYE COLOUR (POTENTIALLY)

+ THE HEIGHT SECTION IS COMPLETELY HALF-ASSED ANYWAYS:

Preface:

It will happen that in some places, the spelled out Latinized form of Greek letters is used, while in others the actual Greek character appears. This is because I wrote out more common terms (e.g. beta-catenin), but sometimes, especially when individual terms were harder to remember or type, I simply copied and pasted them directly.

It may also happen that some passages appear twice because my note-taking app (One note, cagefuel ik) sometimes glitches.

It’s a longer thread my faggots, so I’d recommend putting on a playlist rather than listening to a single song. For example, this one, if you’re too lazy to make one yourself right now:

Spoiler: Disclaimer: DNR this

This material is intended for educational and informational purposes only. It is not intended to provide medical advice, diagnosis, treatment, or a substitute for consultation with a qualified healthcare professional.

The information presented may include experimental findings, emerging research, or simplified explanations and should not be interpreted as established clinical guidance. Some compounds, mechanisms, treatments, or applications discussed may be preclinical or have limited evidence in humans.

Always consult an appropriately qualified healthcare professional before making decisions regarding your health, medications, or treatment. Do not use any information in this material to self-diagnose, self-treat, or change prescribed treatment.

Playlist:

What even is KY-19382? ​

KY-19382, we will shorten it to KY, is a synthetic small molecule that activates the Wnt/β-catenin signaling pathway. Unlike compounds that inhibit Wnt signaling, KY-19382 actually increases Wnt activity. It does this through two main mechanisms: it disrupts the interaction between CXXC5 and Dishevelled (DVL) and inhibits GSK3β, both of which normally act to limit Wnt/β-catenin signaling.

CXXC5 is a negative regulator of the Wnt pathway. It binds to DVL and helps suppress downstream signaling. By interfering with this interaction, KY-19382 removes one of the pathway's main brakes. At the same time, inhibiting GSK3β reduces the degradation of betacatenin, allowing more of it to accumulate and enter the nucleus.

In simple terms:

KY-19382 → CXXC5–DVL inhibition + GSK3β inhibition → increased β-catenin → increased Wnt signaling (Image B)

View attachment 5667764

This is particularly interesting in the context of bone growth. In animal studies, KY-19382 increased activity in the growth plate and was associated with increased proliferation and hypertrophy of chondrocytes, as well as increased longitudinal bone growth of the tibia (more on this later duh).

KY-19382 has also been investigated in other contexts involving Wnt/β-catenin signaling, including hair regeneration and wound healing. Its effects in these areas have likewise been studied mainly in experimental models. (more on this later duh)

Basic Understanding of the Wnt/β-Catenin Signaling Pathway
​

Think of cells as following a command chain. Wnt is one of these signaling systems and is involved in growth, development, and tissue renewal. Among other things, Wnt signaling regulates cell division, cell differentiation (which is relevant for bone development and remodeling), and different stages of cell development.

Under normal conditions, β-catenin is constantly produced but is also continuously marked for degradation by a protein complex known as the destruction complex. One of its main components is GSK3β, which helps phosphorylate β-catenin and target it for degradation. When Wnt signaling is activated, this process is inhibited, allowing β-catenin to accumulate and eventually enter the cell nucleus.

This is where KY becomes relevant. KY inhibits GSK3β, which reduces the degradation of β-catenin and therefore allows more of it to accumulate. At the same time, KY-19382 interferes with the interaction between CXXC5 and Dishevelled (DVL). CXXC5 normally acts as a negative regulator of Wnt signaling, so disrupting this interaction removes another brake on the pathway.

The result is increased Wnt/β-catenin signaling, with more β-catenin available to enter the nucleus and influence gene expression. Among the genes and processes associated with this pathway are those involved in cell proliferation, differentiation, and bone formation, including factors such as RUNX2 and osteocalcin that are relevant to osteoblast differentiation and activity.

Most people here have probably heard of osteoblasts already. If not, I’ll add a short explanation of how bone formation works below.

Spoiler: "Bone Formation, cells and the growthplate"

HUGE CREDITS TO: @Niebvll basically stole everything from him bcs i CBA to write all this shit for you fags

I. Bone Formation​

Bones consist of living tissue made up of three main cell types: osteoblasts, osteocytes, and osteoclasts. All of these cells are embedded within an extracellular matrix, which consists of roughly 45% inorganic minerals (mainly calcium and phosphate compounds), around 30% organic components such as collagen, and water.

II. Relevant Bone Cells​

Osteoblasts are essentially the body's bone-building cells. They develop from mesenchymal stem cells and are found mainly on the surface of bones, particularly in areas where growth, remodeling, or repair is taking place.

Biochemically, osteoblasts are highly active protein producers. Their cytoplasm contains a large amount of rough endoplasmic reticulum because they constantly produce collagen and other matrix proteins. Most of the organic bone matrix consists of type I collagen, which gives bone much of its tensile strength. Other components include osteocalcin, osteopontin, bone sialoprotein, and various proteoglycans.

Once the osteoid, meaning the organic bone matrix, has been produced, osteoblasts release enzymes such as alkaline phosphatase. These promote the deposition of calcium and phosphate, allowing hydroxyapatite crystals to form and harden the bone.

Osteoblasts also help regulate bone remodeling by producing signaling molecules that influence osteoclasts. After completing their work, some osteoblasts die, while others either become osteocytes or remain on the bone surface as inactive cells.

Osteocytes are the most abundant type of bone cell, making up roughly 90–95% of all bone cells. They develop from osteoblasts that become completely embedded in the matrix they produced. They reside in tiny cavities called lacunae and are connected through an extensive network of small channels called canaliculi.

Through these cellular extensions, osteocytes exchange nutrients, ions, and signaling molecules. They act as mechanical sensors for the skeleton: when bone is subjected to mechanical loading, changes in the fluid flow through these channels are detected by the cells. In response, they release signaling molecules that regulate bone formation and resorption.

One particularly important protein is sclerostin, which inhibits osteoblast activity. Osteocytes also release RANKL, which promotes osteoclast formation, and FGF23, a hormone involved in phosphate metabolism and vitamin D regulation. In this way, osteocytes help coordinate bone remodeling and function as a central regulatory system within bone tissue.

Osteoclasts are large, multinucleated cells whose primary function is to break down bone. Unlike osteoblasts, they do not originate from mesenchymal stem cells. Instead, they develop from the hematopoietic lineage, with multiple precursor cells fusing together to form a large cell containing many nuclei.

At the bone surface, osteoclasts form a highly folded membrane structure known as the ruffled border. This area contains proton pumps and chloride channels that allow the cell to pump hydrochloric acid into the resorption compartment. The acid dissolves the mineral component of bone.

Osteoclasts then release enzymes such as cathepsin K and various matrix metalloproteinases, which break down collagen fibers and other organic components. The calcium and phosphate released during this process contribute to the continuous renewal of the skeleton. Without osteoclasts, old or damaged areas of bone could not be properly removed. A healthy skeleton therefore depends on a balance between osteoclast and osteoblast activity.

Osteoprogenitor cells are precursors to osteoblasts. They are found mainly in the periosteum (the outer membrane surrounding bone), the endosteum (the inner lining of bone), and the bone marrow.

They resemble fibroblasts and do not yet have the highly developed protein-producing machinery of mature osteoblasts. Their main function is to provide new osteoblasts when needed. During growth, fracture repair, or normal bone remodeling, they become activated and divide. They then gradually differentiate into mature osteoblasts.

This process is regulated by numerous growth factors and signaling pathways, including BMPs (Bone Morphogenetic Proteins), Wnt signaling, and various hormones. Osteoprogenitor cells therefore provide an important regenerative reserve and are essential for maintaining bone mass throughout life.

Bone-lining cells are inactive osteoblasts that are no longer actively producing matrix. They cover large areas of the bone surface as a thin layer. They help regulate the exchange of calcium and phosphate between bone and blood, protect the bone surface, and support the remodeling process.

When a particular area needs to be remodeled, these cells can release signals that help recruit osteoclasts and osteoblasts. Under certain conditions, they can also become active osteoblasts again.

Chondrocytes are the cells that make up cartilage. In the growth plates of long bones, they are responsible for longitudinal bone growth.

They produce a matrix containing type II collagen, aggrecan, chondroitin sulfate, keratan sulfate, and hyaluronic acid. This matrix binds large amounts of water and gives cartilage its ability to withstand compression.

Within the growth plate, chondrocytes pass through several stages: resting cells, proliferating cells, which divide rapidly, and hypertrophic cells, which become significantly larger. Hypertrophic chondrocytes produce type X collagen and contribute to calcification of the surrounding matrix.

Eventually, these cells often undergo cell death while blood vessels, osteoblasts, and osteoclasts enter the area and the cartilage is replaced by bone. This process, known as endochondral ossification, is responsible for longitudinal bone growth and contributes to the increase in bone volume.

Bone marrow stromal cells (BMSCs) are multipotent mesenchymal stem/stromal cells found in the bone marrow. They can give rise to several different tissue and cell types, including osteoblasts, chondrocytes, adipocytes, fibroblasts, and other mesenchymal cells.

Biochemically, they are characterized by their flexible gene expression, which allows them to respond to different signaling molecules and environmental conditions. Within the bone marrow, they also form an important part of the microenvironment that supports blood-forming stem cells.

They produce growth factors, cytokines, and components of the extracellular matrix and therefore contribute indirectly to blood formation and tissue maintenance.

III. Growth Plates​

The growth plate can broadly be divided into three main zones:

Resting Zone​

This is the uppermost layer of the growth plate, located directly at the end of the bone. The cells here are mostly inactive and divide only rarely. They act as a kind of reserve population of cartilage cells, slowly providing new cells for the layers below when needed.

Proliferative Zone​

This is the active “production zone.” The chondrocytes divide rapidly and arrange themselves into organized columns, similar to stacks of coins.

Each round of proliferation contributes to the overall expansion of the growth plate and therefore to longitudinal bone growth. This is one of the most active regions of the growth plate and plays a major role in determining how quickly a long bone grows.

Hypertrophic Zone​

In this zone, the cells stop dividing and instead begin to grow dramatically in size. Their enlargement contributes to further expansion of the growth plate.

At the same time, they modify the surrounding cartilage matrix and prepare the tissue for mineralization. Eventually, the hypertrophic chondrocytes undergo cell death, blood vessels and bone-forming cells enter the region, and the calcified cartilage is replaced by bone.

This represents the final stage of endochondral ossification, through which cartilage is progressively converted into mature bone.

That is about all you need to know.

KY-19382's Molecular Mechanism of Wnt/β-catenin Activation. (Mini Deep-Dive)​

1. CXXC5​

CXXC5 stands for CXXC-type zinc finger protein 5. It is a relatively small intracellular protein, best known for its role as a negative regulator of the Wnt/β-catenin pathway. The name comes from its characteristic CXXC zinc-finger domain, a structural motive involved in protein interactions.

What makes CXXC5 special is its interaction with Dishevelled (DVL). DVL is one of the important intracellular components of the Wnt pathway. When Wnt binds to the Frizzled/LRP5/6 receptor complex at the cell surface, DVL is recruited and helps pass the signal further into the cell. From there, the signaling cascade eventually leads to stabilization of β-catenin and activation of Wnt-responsive genes.

CXXC5 puts a brake on this process. It can bind to DVL and interfere with its ability to efficiently transmit the Wnt signal. So, rather than blocking Wnt before it reaches the cell, CXXC5 acts further downstream (like many other compounds), at the level of the intracellular signaling machinery.

There is also a feedback mechanism involved. Activation of Wnt signaling can increase the expression of CXXC5 itself. Simply put nigger, the pathway contains its own mechanism for putting the brakes on after being activated. More Wnt signaling can lead to more CXXC5, which then interacts with DVL and helps limit further signaling.

It is part of the system that determines how strong and how long the Wnt signal remains active.

2. GSK3β​

Now we get to the second part of KY19382's mechanism: GSK3β, or glycogen synthase kinase 3 beta.

GSK3β is a kinase, meaning its job is to add phosphate groups to other proteins (phosphorylation wallahi most of you niggers must know this). One of its most important jobs is controlling the amount of β-catenin inside the cell.

Under normal conditions, β-catenin is constantly being produced, but it doesn't simply sit around and accumulate. When Wnt signaling is inactive, β-catenin is captured by the so-called destruction complex, where it is phosphorylated by CK1 and GSK3β. These phosphorylation marks essentially label β-catenin for destruction. It is then ubiquitinated (I just learned this term when doing research ) and sent to the proteasome, where it gets broken down.

So, very simplified:

GSK3β active → β-catenin gets phosphorylated → β-catenin gets degraded → little β-catenin reaches the nucleus

This is one of the main reasons the cell can keep Wnt signaling switched off when there is no Wnt signal telling it to do otherwise.

When Wnt signaling is activated, however, this destruction process is inhibited. GSK3β can no longer efficiently phosphorylate β-catenin, so β-catenin becomes more stable, accumulates in the cytoplasm, and can eventually enter the nucleus. There it interacts with TCF/LEF transcription factors and helps activate Wnt-responsive genes.

And this is where KY-19382 comes in for a second time.

KY-19382 inhibits GSK3β, meaning β-catenin is no longer phosphorylated and degraded as efficiently. The result is increased β-catenin stability and accumulation, which pushes the pathway toward stronger Wnt/β-catenin signaling.

So we now have two separate effects of KY-19382:

CXXC5–DVL inhibition
→ removes a negative regulator of Wnt signal transmission

GSK3β inhibition
→ reduces β-catenin degradation

↑ β-catenin → ↑ nuclear β-catenin → ↑ Wnt target gene activity

This is what sets KY-19382 apart from other indirubin derivatives or Wnt/β-catenin compounds: it targets the pathway at two separate points. Fascinating right faggots? right? Yeah fuck all of you, especially the nigha @ragingmanlet.

NOTE: Everything I've covered in this molecular section is a very broad and simplified overview of a much more complicated pathway

For example, you could go much deeper into almost every step we've discussed:

• The different Frizzled receptors and LRP5/6 co-receptors and how individual Wnt ligands interact with them
• The different domains of DVL and exactly how DVL changes its conformation and signaling behavior
• The CXXC5–DVL interaction, including the C-terminal region of CXXC5 and the PDZ domain of DVL
• How KY-19382 interacts with this system at the molecular level and what is known versus what has only been proposed through structural modeling
• The individual phosphorylation steps carried out by CK1 and GSK3β
• The roles of Axin, APC, β-TrCP, and the other components of the β-catenin destruction complex
• How β-catenin moves between the cytoplasm and nucleus
• The interaction between β-catenin and TCF/LEF transcription factors
• The many different genes and transcriptional programs that can be influenced downstream
• The feedback mechanisms that regulate Wnt signaling, including proteins such as CXXC5, SFRPs, DKKs, and others
• How ubiquitination and proteasomal degradation regulate the abundance of signaling proteins such as CXXC5 and β-catenin

But WE yes WE as Looksmaxxers dgaf about this science nerd thingy duh

We only care about the JUICY Stuff...

KY-19382 for longitudinal bone growth (Height nigga)​

So how could increasing Wnt/β-catenin signaling actually affect longitudinal bone growth?

These cells continuously pass through different stages: they proliferate, differentiate, become hypertrophic, and are eventually replaced by bone. The rate at which this process happens has a direct effect on how quickly the bone elongates.

Wnt/β-catenin signaling is involved throughout this process. When Wnt signaling is increased, β-catenin becomes more stable, accumulates in the cell, and enters the nucleus. There it interacts with TCF/LEF transcription factors and changes the expression of Wnt-responsive genes. In growth-plate chondrocytes, this can affect both proliferation and differentiation.

In the proliferative zone, increased Wnt/β-catenin activity can support the production of new chondrocytes. More rounds of cell division mean more cells are available to move through the growth plate and eventually enter hypertrophic differentiation. The important point is that longitudinal growth depends not only on how large individual chondrocytes become, but also on how many cells are being produced and how quickly they progress through the growth plate.

Wnt signaling also affects the transition toward hypertrophy. β-catenin activity is linked to factors such as RUNX2 and other genes involved in chondrocyte maturation. As chondrocytes become hypertrophic, they increase in volume and produce a different set of extracellular-matrix proteins, including collagen X. The cartilage is then progressively remodeled and replaced by bone on the metaphyseal side of the growth plate.

So increasing Wnt/β-catenin activity can affect several parts of the same process:

Wnt/β-catenin ↑ → chondrocyte proliferation ↑ → more chondrocytes enter the growth-plate program → differentiation and hypertrophy ↑ → more cartilage is produced for replacement by bone → longitudinal growth can increase

The growth plate does not stay active forever (fusion). During puberty, its activity gradually declines and the plate becomes senescent. One of the proteins involved in this process is CXXC5.

CXXC5 acts as a negative regulator of Wnt/β-catenin signaling by interacting with Dishevelled (DVL). As CXXC5 increases, this inhibitory effect becomes stronger and Wnt signaling is reduced. That means less β-catenin reaches the nucleus and the expression of genes associated with active chondrocyte behavior decreases.

Estrogen signaling increases during puberty, and estrogen can increase CXXC5 expression in growth-plate chondrocytes. As CXXC5 rises, Wnt/β-catenin signaling is suppressed and the growth plate gradually becomes less active.

In simplified form:

Estrogen ↑ → CXXC5 ↑ → Wnt/β-catenin ↓ → growth-plate activity ↓ → senescence of the resting zone (fusion)

Over time, this contributes to the normal shutdown of longitudinal bone growth. In humans, the process eventually ends with epiphyseal fusion, when the growth plate is replaced by bone and there is no longer an active cartilage plate capable of producing further longitudinal growth.

If CXXC5 helps suppress Wnt signaling as the growth plate ages, then interfering with CXXC5 could have the opposite effect: maintaining β-catenin signaling, keeping chondrocytes active for longer, and potentially delaying some of the changes associated with growth-plate senescence. (Translation for Iqlets: Keep the Plates open for longer and increase Velocity)

TLR: Estrogenic activity (binding ERA AF2) increases CXXC5, which leads to decreased growth plate activity and this ends and "depletes/kills" the resting zone and replaces it with bone (luncae)

Now, Does KY have any evidence or is this just speculation?

Actually, we do have evidence and let me tell you my friend, it's looking bright.

“CXXC5 mediates growth plate senescence and is a target for enhancement of longitudinal bone growth” (PMID30971423)

Note: I tried a type of a story-time telling. Inspo @Tesarossa
​

So what actually happend?​

Instead of starting with KY-19382, our dear researchers looked at growth plates at different stages of development and compared the expression of CXXC5 with markers of Wnt/β-catenin activity and chondrogenesis.

They found that as the animals progressed through puberty, CXXC5 expression gradually increased (likely due to increased estrogen-signaling) . At the same time, β-catenin and several markers associated with active chondrocytes decreased.

So there is a pretty clear pattern:

pubertal progression → CXXC5 ↑ → Wnt/β-catenin activity ↓

But this still didn't tell them whether CXXC5 was actually involved in causing the decline, or whether it was simply changing alongside it.

So they went one step further.

The researchers then asked what happens if CXXC5 is removed altogether. They used mice in which the Cxxc5 gene had been knocked out and compared them with normal mice.

And the difference was noticeable.

As the normal mice aged, their growth plates showed the usual signs of senescence: fewer active chondrocytes, reduced proliferation and reduced Wnt/β-catenin activity. The Cxxc5-knockout mice retained more of this activity at later ages.

They also had longer tibia.

The researchers then asked whether they needed to remove CXXC5 completely to get this effect.

They already knew that CXXC5 interacts with Dishevelled (DVL) and suppresses Wnt signaling through this interaction. So instead of deleting the entire gene, they used a blocking peptide, PTD-DBMP, to interfere specifically with the CXXC5–DVL interaction.

Again, blocking this interaction increased β-catenin signaling and increased the number of proliferating and hypertrophic chondrocytes in the growth plate.

At this point, the idea was becoming much more interesting:

CXXC5 ↑ → Wnt signaling ↓ → growth-plate activity ↓

while interfering with CXXC5 gave them the opposite direction.

But a peptide or a complete gene knockout isn't exactly the same thing as having a small molecule that could be used experimentally.

So the researchers went looking for one.

They screened 2,280 compounds for molecules capable of interfering with the CXXC5–DVL interaction. This eventually led them to indirubin-based compounds and, from there, to the compound we're interested in:

KY-19382. (our goat)

But finding a compound that works in a screening assay isn't enough. They needed to test whether KY actually affected both of the targets they were interested in.

First, they tested the CXXC5DVL interaction directly. KY-19382 inhibited this interaction with an IC₅₀ of approximately 19 nM.

They then tested GSK3β kinase activity separately. KY-19382 inhibited GSK3β with an IC₅₀ of approximately 10 nM.

The next question was whether those two effects actually translated into increased Wnt/β-catenin signaling inside cells.

For that, they used the TOPFlash reporter assay, which is commonly used to measure β-catenin/TCF-dependent transcription. Increasing concentrations of KY-19382 increased TOPFlash activity, showing that the compound was activating Wnt/β-catenin signaling in the cells.

They then went a step further and looked at what was happening to the proteins themselves.

In ATDC5 chondrocytes, KY-19382 increased β-catenin while reducing the active forms of GSK3α/β. They also performed an immunoprecipitation experiment to directly examine the CXXC5–DVL interaction. After KY treatment, the interaction was reduced.

And finally, they looked at where the β-catenin was going.

After treatment with KY-19382, substantially more β-catenin was detected in the nucleus of the chondrocytes.

So what happens when they put KY-19382 into mice?​

Now that they had shown that KY-19382 could activate Wnt/β-catenin signaling in cells, the researchers wanted to see whether the same thing happened in an actual growth plate.

They started with 7-week-old mice, which are already approaching the later stages of pubertal growth.

The mice received 0.1 mg/kg KY-19382 every day for 2 weeks. After treatment, the researchers examined the tibial growth plates and compared them with vehicle-treated controls.

The growth plate was larger in the KY-treated animals.

But they didn't just measure its overall size. They also looked at what the cells inside the growth plate were actually doing.

They used BrdU staining to identify proliferating cells and RUNX2 as a marker associated with hypertrophic differentiation. Both were increased after KY-19382 treatment.

They also looked at β-catenin itself.

And this was especially clear: nuclear β-catenin was strongly increased in the growth-plate chondrocytes.

So the change in growth-plate size came together with molecular and cellular changes that fit with increased Wnt/β-catenin activity.

They then repeated the experiment in 3-week-old mice, which are still undergoing rapid growth.

Again, the animals received 0.1 mg/kg KY-19382 daily for 2 weeks.

This time, the total growth-plate height increased, as did the heights of its individual zones. The number of BrdU-positive cells also increased, showing that more chondrocytes were actively proliferating.

But there was another question they needed to rule out.

If the hypertrophic zone becomes larger, that doesn't automatically mean the growth plate is producing more cells. It could also happen if the cartilage is simply being removed more slowly at the cartilage-to-bone interface.

So they looked at TRAP-positive foci, which mark osteoclast activity at this interface.

In the young mice, there was no significant difference in TRAP-positive foci between the KY-treated and control groups.

That makes a simple explanation based on reduced cartilage resorption less convincing.

Interestingly, the result was different in the older 7-week-old animals: KY-19382 increased TRAP-positive foci. The researchers interpreted this as evidence that KY was not merely accumulating cartilage in the growth plate, but was actually promoting the overall maturation process.

So by this point, the picture was becoming much more concrete.

And then they measured the bone itself​

The short-term experiments had shown that KY-19382 could make the growth plate more active. But the researchers wanted to know whether that effect was large enough to change the final length of the bone.

So they designed a much longer experiment.

They started with 3-week-old male C57BL/6 mice and treated them with 0.1 mg/kg KY-19382 by intraperitoneal injection every day for 10 weeks. The control animals received the vehicle instead.

This means the mice were followed from roughly 3 weeks of age to 13 weeks of age, covering a substantial part of the period in which their longitudinal growth normally slows down.

After the 10 weeks, the researchers took radiographs and measured the tibiae.

And this time, the result wasn't just a change in a staining pattern or in the appearance of the growth plate.

The KY-19382-treated mice had significantly longer tibiae than the vehicle-treated mice.

The reported difference was statistically significant, with P < 0.0005.

That gives the study an important progression:

There is, however, an important distinction here.

This experiment demonstrates the effect of KY-19382 as a compound. It does not prove that the increase in tibial length came exclusively from CXXC5 inhibition, because KY-19382 also inhibits GSK3β. (We dgaf about this tho)

The earlier Cxxc5 knockout experiments are therefore important for the CXXC5-specific part of the story, while the KY experiments show what happens when both of these mechanisms are affected by the compound.

The researchers also looked for obvious signs of toxicity during the long-term treatment. They reported no significant difference in body weight and found no histological abnormalities in the examined articular cartilage or liver.

That is reassuring within the limits of this particular experiment, but it doesn't turn KY-19382 into a proven safe compound. These were still preclinical mouse experiments, using a compound that has not been established as a human treatment.

At this point, the researchers had shown something quite substantial in mice:

CXXC5 is associated with the loss of growth-plate activity during maturation, removing or interfering with CXXC5 preserves Wnt/β-catenin signaling, and pharmacological activation with KY-19382 was associated with increased growth-plate activity and, after prolonged treatment, increased tibial length.

But the researchers still had another piece of the puzzle to address:

Why does CXXC5 increase during puberty in the first place?

That brings us back to estrogen.

The researchers then asked whether estrogen could be the signal driving this increase in CXXC5 during puberty.

They treated human chondrocytes with 17β-estradiol (E2) and found that CXXC5 expression increased after estrogen exposure, while β-catenin levels decreased. So the relationship seen during puberty could also be reproduced experimentally: more estrogen, more CXXC5, less active Wnt/β-catenin signaling.

They then looked at what this actually meant for the growth plate. When tibial growth plate cultures were treated with E2, longitudinal growth was reduced, together with reductions in the proliferative and hypertrophic zones. In other words, estrogen was not simply changing CXXC5 expression in isolation. It was associated with the structural changes that accompany growth plate senescence.

The strongest evidence came from the Cxxc5 knockout mice. When estrogen was given to normal mice, the growth plate developed the expected senescent changes. But when the same experiment was performed in mice lacking Cxxc5, most of that estrogen-induced phenotype was lost.

That places CXXC5 downstream of estrogen in this model. The study therefore supports a mechanism in which the rise in estrogen during puberty increases CXXC5, CXXC5 suppresses Wnt/β-catenin signaling, and the resulting reduction in chondrocyte activity contributes to growth plate senescence.

And that gives the whole study a much more complete chain:

Instead of simply adding a growth-promoting signal from outside, the compound interferes with one of the mechanisms that normally suppresses Wnt signaling. It blocks the CXXC5–DVL interaction while also inhibiting GSK3β, giving β-catenin two routes to remain active.

So the paper is essentially connecting two levels of the problem: the developmental signal that increases CXXC5 during puberty, and the molecular machinery through which CXXC5 reduces Wnt activity in the growth plate. The experiments with KY-19382 then ask whether interfering with that machinery is enough to preserve growth plate activity and extend longitudinal bone growth.

In the mouse experiments, the answer was yes: the growth plate remained more active, chondrocyte proliferation and maturation were increased, and prolonged treatment produced measurable increases in tibial length.

So what does the mouse dose mean in humans?​

The researchers used KY-19382 at 0.1 mg/kg once daily in the mouse experiments. The short-term studies lasted 2 weeks, while the long-term experiment treated the mice daily for 10 weeks, from 3 to 13 weeks of age.

A common preclinical approach is to use body-surface-area scaling, which gives a rough human-equivalent dose (HED).

For mice, the standard Km factor is 3, compared with 37 for an adult human:

HED = animal dose × (mouse Km / human Km)

So for the dose used in this study:

0.1 mg/kg × 3/37 ≈ 0.0081 mg/kg

That corresponds to roughly:

• 60 kg human → 0.49 mg/day
• 70 kg human → 0.57 mg/day
• 80 kg human → 0.65 mg/day

So, purely as a body-surface-area conversion, the 0.1 mg/kg mouse dose corresponds to about 0.5–0.65 mg in a 60–80 kg adult human.

Simple math duh .

Administration

I honestly CBA to make a guide on administration and lowkey want to go to sleep.

You have 2 choices:

1. Oral

Guide: Geometrically dilute the powder and put it in capsules (duh)
Note: You will need to account for a lower Bioavailibility

2. SubQ

Guide: Watch my friends video on TT on how to make a DIY solution:


Sources and Price:

Cost per Gram: Usually varies between 200$-600$

look on sites such as Echemi or Lookchem for good vendors.

If you can't find a source DM me.

I won't even correct my grammar I CBA Fuck all of you,

YES I USED AI TO FORMAT EVERYTHING NIGGER, IT'S 2026. Why would I not?



​

Good job

Its a lot of text so I will take a look later

But mirin

 

[Songe]

I’ve had 5g of KY stored in my freezer for months now and haven’t touched it once. Given that my main issue is hair loss wouldn’t applying it topically make the most sense? I’m still trying to figure out the best route to take rn

 

[rsj]

Credits @Niebvll, got inspired by this thread in german. Make sure to rep and follow him: HERE

FUCK THIS THREAD I JUST WASTED MY TIME WALLAHI. GO DO SOMETHING BETTER WITH YOUR TIME OF DAY. THIS THREAD IS NOT COMPLETED IN THE SLIGHTEST

I COULD HAVE DONE ITS EFFECT ON
- FACIAL BONES
- HAIR
- EYE COLOUR (POTENTIALLY)

+ THE HEIGHT SECTION IS COMPLETELY HALF-ASSED ANYWAYS:

Preface:

It will happen that in some places, the spelled out Latinized form of Greek letters is used, while in others the actual Greek character appears. This is because I wrote out more common terms (e.g. beta-catenin), but sometimes, especially when individual terms were harder to remember or type, I simply copied and pasted them directly.

It may also happen that some passages appear twice because my note-taking app (One note, cagefuel ik) sometimes glitches.

It’s a longer thread my faggots, so I’d recommend putting on a playlist rather than listening to a single song. For example, this one, if you’re too lazy to make one yourself right now:

Spoiler: Disclaimer: DNR this

This material is intended for educational and informational purposes only. It is not intended to provide medical advice, diagnosis, treatment, or a substitute for consultation with a qualified healthcare professional.

The information presented may include experimental findings, emerging research, or simplified explanations and should not be interpreted as established clinical guidance. Some compounds, mechanisms, treatments, or applications discussed may be preclinical or have limited evidence in humans.

Always consult an appropriately qualified healthcare professional before making decisions regarding your health, medications, or treatment. Do not use any information in this material to self-diagnose, self-treat, or change prescribed treatment.

Playlist:

What even is KY-19382? ​

KY-19382, we will shorten it to KY, is a synthetic small molecule that activates the Wnt/β-catenin signaling pathway. Unlike compounds that inhibit Wnt signaling, KY-19382 actually increases Wnt activity. It does this through two main mechanisms: it disrupts the interaction between CXXC5 and Dishevelled (DVL) and inhibits GSK3β, both of which normally act to limit Wnt/β-catenin signaling.

CXXC5 is a negative regulator of the Wnt pathway. It binds to DVL and helps suppress downstream signaling. By interfering with this interaction, KY-19382 removes one of the pathway's main brakes. At the same time, inhibiting GSK3β reduces the degradation of betacatenin, allowing more of it to accumulate and enter the nucleus.

In simple terms:

KY-19382 → CXXC5–DVL inhibition + GSK3β inhibition → increased β-catenin → increased Wnt signaling (Image B)

View attachment 5667764

This is particularly interesting in the context of bone growth. In animal studies, KY-19382 increased activity in the growth plate and was associated with increased proliferation and hypertrophy of chondrocytes, as well as increased longitudinal bone growth of the tibia (more on this later duh).

KY-19382 has also been investigated in other contexts involving Wnt/β-catenin signaling, including hair regeneration and wound healing. Its effects in these areas have likewise been studied mainly in experimental models. (more on this later duh)

Basic Understanding of the Wnt/β-Catenin Signaling Pathway
​

Think of cells as following a command chain. Wnt is one of these signaling systems and is involved in growth, development, and tissue renewal. Among other things, Wnt signaling regulates cell division, cell differentiation (which is relevant for bone development and remodeling), and different stages of cell development.

Under normal conditions, β-catenin is constantly produced but is also continuously marked for degradation by a protein complex known as the destruction complex. One of its main components is GSK3β, which helps phosphorylate β-catenin and target it for degradation. When Wnt signaling is activated, this process is inhibited, allowing β-catenin to accumulate and eventually enter the cell nucleus.

This is where KY becomes relevant. KY inhibits GSK3β, which reduces the degradation of β-catenin and therefore allows more of it to accumulate. At the same time, KY-19382 interferes with the interaction between CXXC5 and Dishevelled (DVL). CXXC5 normally acts as a negative regulator of Wnt signaling, so disrupting this interaction removes another brake on the pathway.

The result is increased Wnt/β-catenin signaling, with more β-catenin available to enter the nucleus and influence gene expression. Among the genes and processes associated with this pathway are those involved in cell proliferation, differentiation, and bone formation, including factors such as RUNX2 and osteocalcin that are relevant to osteoblast differentiation and activity.

Most people here have probably heard of osteoblasts already. If not, I’ll add a short explanation of how bone formation works below.

Spoiler: "Bone Formation, cells and the growthplate"

HUGE CREDITS TO: @Niebvll basically stole everything from him bcs i CBA to write all this shit for you fags

I. Bone Formation​

Bones consist of living tissue made up of three main cell types: osteoblasts, osteocytes, and osteoclasts. All of these cells are embedded within an extracellular matrix, which consists of roughly 45% inorganic minerals (mainly calcium and phosphate compounds), around 30% organic components such as collagen, and water.

II. Relevant Bone Cells​

Osteoblasts are essentially the body's bone-building cells. They develop from mesenchymal stem cells and are found mainly on the surface of bones, particularly in areas where growth, remodeling, or repair is taking place.

Biochemically, osteoblasts are highly active protein producers. Their cytoplasm contains a large amount of rough endoplasmic reticulum because they constantly produce collagen and other matrix proteins. Most of the organic bone matrix consists of type I collagen, which gives bone much of its tensile strength. Other components include osteocalcin, osteopontin, bone sialoprotein, and various proteoglycans.

Once the osteoid, meaning the organic bone matrix, has been produced, osteoblasts release enzymes such as alkaline phosphatase. These promote the deposition of calcium and phosphate, allowing hydroxyapatite crystals to form and harden the bone.

Osteoblasts also help regulate bone remodeling by producing signaling molecules that influence osteoclasts. After completing their work, some osteoblasts die, while others either become osteocytes or remain on the bone surface as inactive cells.

Osteocytes are the most abundant type of bone cell, making up roughly 90–95% of all bone cells. They develop from osteoblasts that become completely embedded in the matrix they produced. They reside in tiny cavities called lacunae and are connected through an extensive network of small channels called canaliculi.

Through these cellular extensions, osteocytes exchange nutrients, ions, and signaling molecules. They act as mechanical sensors for the skeleton: when bone is subjected to mechanical loading, changes in the fluid flow through these channels are detected by the cells. In response, they release signaling molecules that regulate bone formation and resorption.

One particularly important protein is sclerostin, which inhibits osteoblast activity. Osteocytes also release RANKL, which promotes osteoclast formation, and FGF23, a hormone involved in phosphate metabolism and vitamin D regulation. In this way, osteocytes help coordinate bone remodeling and function as a central regulatory system within bone tissue.

Osteoclasts are large, multinucleated cells whose primary function is to break down bone. Unlike osteoblasts, they do not originate from mesenchymal stem cells. Instead, they develop from the hematopoietic lineage, with multiple precursor cells fusing together to form a large cell containing many nuclei.

At the bone surface, osteoclasts form a highly folded membrane structure known as the ruffled border. This area contains proton pumps and chloride channels that allow the cell to pump hydrochloric acid into the resorption compartment. The acid dissolves the mineral component of bone.

Osteoclasts then release enzymes such as cathepsin K and various matrix metalloproteinases, which break down collagen fibers and other organic components. The calcium and phosphate released during this process contribute to the continuous renewal of the skeleton. Without osteoclasts, old or damaged areas of bone could not be properly removed. A healthy skeleton therefore depends on a balance between osteoclast and osteoblast activity.

Osteoprogenitor cells are precursors to osteoblasts. They are found mainly in the periosteum (the outer membrane surrounding bone), the endosteum (the inner lining of bone), and the bone marrow.

They resemble fibroblasts and do not yet have the highly developed protein-producing machinery of mature osteoblasts. Their main function is to provide new osteoblasts when needed. During growth, fracture repair, or normal bone remodeling, they become activated and divide. They then gradually differentiate into mature osteoblasts.

This process is regulated by numerous growth factors and signaling pathways, including BMPs (Bone Morphogenetic Proteins), Wnt signaling, and various hormones. Osteoprogenitor cells therefore provide an important regenerative reserve and are essential for maintaining bone mass throughout life.

Bone-lining cells are inactive osteoblasts that are no longer actively producing matrix. They cover large areas of the bone surface as a thin layer. They help regulate the exchange of calcium and phosphate between bone and blood, protect the bone surface, and support the remodeling process.

When a particular area needs to be remodeled, these cells can release signals that help recruit osteoclasts and osteoblasts. Under certain conditions, they can also become active osteoblasts again.

Chondrocytes are the cells that make up cartilage. In the growth plates of long bones, they are responsible for longitudinal bone growth.

They produce a matrix containing type II collagen, aggrecan, chondroitin sulfate, keratan sulfate, and hyaluronic acid. This matrix binds large amounts of water and gives cartilage its ability to withstand compression.

Within the growth plate, chondrocytes pass through several stages: resting cells, proliferating cells, which divide rapidly, and hypertrophic cells, which become significantly larger. Hypertrophic chondrocytes produce type X collagen and contribute to calcification of the surrounding matrix.

Eventually, these cells often undergo cell death while blood vessels, osteoblasts, and osteoclasts enter the area and the cartilage is replaced by bone. This process, known as endochondral ossification, is responsible for longitudinal bone growth and contributes to the increase in bone volume.

Bone marrow stromal cells (BMSCs) are multipotent mesenchymal stem/stromal cells found in the bone marrow. They can give rise to several different tissue and cell types, including osteoblasts, chondrocytes, adipocytes, fibroblasts, and other mesenchymal cells.

Biochemically, they are characterized by their flexible gene expression, which allows them to respond to different signaling molecules and environmental conditions. Within the bone marrow, they also form an important part of the microenvironment that supports blood-forming stem cells.

They produce growth factors, cytokines, and components of the extracellular matrix and therefore contribute indirectly to blood formation and tissue maintenance.

III. Growth Plates​

The growth plate can broadly be divided into three main zones:

Resting Zone​

This is the uppermost layer of the growth plate, located directly at the end of the bone. The cells here are mostly inactive and divide only rarely. They act as a kind of reserve population of cartilage cells, slowly providing new cells for the layers below when needed.

Proliferative Zone​

This is the active “production zone.” The chondrocytes divide rapidly and arrange themselves into organized columns, similar to stacks of coins.

Each round of proliferation contributes to the overall expansion of the growth plate and therefore to longitudinal bone growth. This is one of the most active regions of the growth plate and plays a major role in determining how quickly a long bone grows.

Hypertrophic Zone​

In this zone, the cells stop dividing and instead begin to grow dramatically in size. Their enlargement contributes to further expansion of the growth plate.

At the same time, they modify the surrounding cartilage matrix and prepare the tissue for mineralization. Eventually, the hypertrophic chondrocytes undergo cell death, blood vessels and bone-forming cells enter the region, and the calcified cartilage is replaced by bone.

This represents the final stage of endochondral ossification, through which cartilage is progressively converted into mature bone.

That is about all you need to know.

KY-19382's Molecular Mechanism of Wnt/β-catenin Activation. (Mini Deep-Dive)​

1. CXXC5​

CXXC5 stands for CXXC-type zinc finger protein 5. It is a relatively small intracellular protein, best known for its role as a negative regulator of the Wnt/β-catenin pathway. The name comes from its characteristic CXXC zinc-finger domain, a structural motive involved in protein interactions.

What makes CXXC5 special is its interaction with Dishevelled (DVL). DVL is one of the important intracellular components of the Wnt pathway. When Wnt binds to the Frizzled/LRP5/6 receptor complex at the cell surface, DVL is recruited and helps pass the signal further into the cell. From there, the signaling cascade eventually leads to stabilization of β-catenin and activation of Wnt-responsive genes.

CXXC5 puts a brake on this process. It can bind to DVL and interfere with its ability to efficiently transmit the Wnt signal. So, rather than blocking Wnt before it reaches the cell, CXXC5 acts further downstream (like many other compounds), at the level of the intracellular signaling machinery.

There is also a feedback mechanism involved. Activation of Wnt signaling can increase the expression of CXXC5 itself. Simply put nigger, the pathway contains its own mechanism for putting the brakes on after being activated. More Wnt signaling can lead to more CXXC5, which then interacts with DVL and helps limit further signaling.

It is part of the system that determines how strong and how long the Wnt signal remains active.

2. GSK3β​

Now we get to the second part of KY19382's mechanism: GSK3β, or glycogen synthase kinase 3 beta.

GSK3β is a kinase, meaning its job is to add phosphate groups to other proteins (phosphorylation wallahi most of you niggers must know this). One of its most important jobs is controlling the amount of β-catenin inside the cell.

Under normal conditions, β-catenin is constantly being produced, but it doesn't simply sit around and accumulate. When Wnt signaling is inactive, β-catenin is captured by the so-called destruction complex, where it is phosphorylated by CK1 and GSK3β. These phosphorylation marks essentially label β-catenin for destruction. It is then ubiquitinated (I just learned this term when doing research ) and sent to the proteasome, where it gets broken down.

So, very simplified:

GSK3β active → β-catenin gets phosphorylated → β-catenin gets degraded → little β-catenin reaches the nucleus

This is one of the main reasons the cell can keep Wnt signaling switched off when there is no Wnt signal telling it to do otherwise.

When Wnt signaling is activated, however, this destruction process is inhibited. GSK3β can no longer efficiently phosphorylate β-catenin, so β-catenin becomes more stable, accumulates in the cytoplasm, and can eventually enter the nucleus. There it interacts with TCF/LEF transcription factors and helps activate Wnt-responsive genes.

And this is where KY-19382 comes in for a second time.

KY-19382 inhibits GSK3β, meaning β-catenin is no longer phosphorylated and degraded as efficiently. The result is increased β-catenin stability and accumulation, which pushes the pathway toward stronger Wnt/β-catenin signaling.

So we now have two separate effects of KY-19382:

CXXC5–DVL inhibition
→ removes a negative regulator of Wnt signal transmission

GSK3β inhibition
→ reduces β-catenin degradation

↑ β-catenin → ↑ nuclear β-catenin → ↑ Wnt target gene activity

This is what sets KY-19382 apart from other indirubin derivatives or Wnt/β-catenin compounds: it targets the pathway at two separate points. Fascinating right faggots? right? Yeah fuck all of you, especially the nigha @ragingmanlet.

NOTE: Everything I've covered in this molecular section is a very broad and simplified overview of a much more complicated pathway

For example, you could go much deeper into almost every step we've discussed:

• The different Frizzled receptors and LRP5/6 co-receptors and how individual Wnt ligands interact with them
• The different domains of DVL and exactly how DVL changes its conformation and signaling behavior
• The CXXC5–DVL interaction, including the C-terminal region of CXXC5 and the PDZ domain of DVL
• How KY-19382 interacts with this system at the molecular level and what is known versus what has only been proposed through structural modeling
• The individual phosphorylation steps carried out by CK1 and GSK3β
• The roles of Axin, APC, β-TrCP, and the other components of the β-catenin destruction complex
• How β-catenin moves between the cytoplasm and nucleus
• The interaction between β-catenin and TCF/LEF transcription factors
• The many different genes and transcriptional programs that can be influenced downstream
• The feedback mechanisms that regulate Wnt signaling, including proteins such as CXXC5, SFRPs, DKKs, and others
• How ubiquitination and proteasomal degradation regulate the abundance of signaling proteins such as CXXC5 and β-catenin

But WE yes WE as Looksmaxxers dgaf about this science nerd thingy duh

We only care about the JUICY Stuff...

KY-19382 for longitudinal bone growth (Height nigga)​

So how could increasing Wnt/β-catenin signaling actually affect longitudinal bone growth?

These cells continuously pass through different stages: they proliferate, differentiate, become hypertrophic, and are eventually replaced by bone. The rate at which this process happens has a direct effect on how quickly the bone elongates.

Wnt/β-catenin signaling is involved throughout this process. When Wnt signaling is increased, β-catenin becomes more stable, accumulates in the cell, and enters the nucleus. There it interacts with TCF/LEF transcription factors and changes the expression of Wnt-responsive genes. In growth-plate chondrocytes, this can affect both proliferation and differentiation.

In the proliferative zone, increased Wnt/β-catenin activity can support the production of new chondrocytes. More rounds of cell division mean more cells are available to move through the growth plate and eventually enter hypertrophic differentiation. The important point is that longitudinal growth depends not only on how large individual chondrocytes become, but also on how many cells are being produced and how quickly they progress through the growth plate.

Wnt signaling also affects the transition toward hypertrophy. β-catenin activity is linked to factors such as RUNX2 and other genes involved in chondrocyte maturation. As chondrocytes become hypertrophic, they increase in volume and produce a different set of extracellular-matrix proteins, including collagen X. The cartilage is then progressively remodeled and replaced by bone on the metaphyseal side of the growth plate.

So increasing Wnt/β-catenin activity can affect several parts of the same process:

Wnt/β-catenin ↑ → chondrocyte proliferation ↑ → more chondrocytes enter the growth-plate program → differentiation and hypertrophy ↑ → more cartilage is produced for replacement by bone → longitudinal growth can increase

The growth plate does not stay active forever (fusion). During puberty, its activity gradually declines and the plate becomes senescent. One of the proteins involved in this process is CXXC5.

CXXC5 acts as a negative regulator of Wnt/β-catenin signaling by interacting with Dishevelled (DVL). As CXXC5 increases, this inhibitory effect becomes stronger and Wnt signaling is reduced. That means less β-catenin reaches the nucleus and the expression of genes associated with active chondrocyte behavior decreases.

Estrogen signaling increases during puberty, and estrogen can increase CXXC5 expression in growth-plate chondrocytes. As CXXC5 rises, Wnt/β-catenin signaling is suppressed and the growth plate gradually becomes less active.

In simplified form:

Estrogen ↑ → CXXC5 ↑ → Wnt/β-catenin ↓ → growth-plate activity ↓ → senescence of the resting zone (fusion)

Over time, this contributes to the normal shutdown of longitudinal bone growth. In humans, the process eventually ends with epiphyseal fusion, when the growth plate is replaced by bone and there is no longer an active cartilage plate capable of producing further longitudinal growth.

If CXXC5 helps suppress Wnt signaling as the growth plate ages, then interfering with CXXC5 could have the opposite effect: maintaining β-catenin signaling, keeping chondrocytes active for longer, and potentially delaying some of the changes associated with growth-plate senescence. (Translation for Iqlets: Keep the Plates open for longer and increase Velocity)

TLR: Estrogenic activity (binding ERA AF2) increases CXXC5, which leads to decreased growth plate activity and this ends and "depletes/kills" the resting zone and replaces it with bone (luncae)

Now, Does KY have any evidence or is this just speculation?

Actually, we do have evidence and let me tell you my friend, it's looking bright.

“CXXC5 mediates growth plate senescence and is a target for enhancement of longitudinal bone growth” (PMID30971423)

Note: I tried a type of a story-time telling. Inspo @Tesarossa
​

So what actually happend?​

Instead of starting with KY-19382, our dear researchers looked at growth plates at different stages of development and compared the expression of CXXC5 with markers of Wnt/β-catenin activity and chondrogenesis.

They found that as the animals progressed through puberty, CXXC5 expression gradually increased (likely due to increased estrogen-signaling) . At the same time, β-catenin and several markers associated with active chondrocytes decreased.

So there is a pretty clear pattern:

pubertal progression → CXXC5 ↑ → Wnt/β-catenin activity ↓

But this still didn't tell them whether CXXC5 was actually involved in causing the decline, or whether it was simply changing alongside it.

So they went one step further.

The researchers then asked what happens if CXXC5 is removed altogether. They used mice in which the Cxxc5 gene had been knocked out and compared them with normal mice.

And the difference was noticeable.

As the normal mice aged, their growth plates showed the usual signs of senescence: fewer active chondrocytes, reduced proliferation and reduced Wnt/β-catenin activity. The Cxxc5-knockout mice retained more of this activity at later ages.

They also had longer tibia.

The researchers then asked whether they needed to remove CXXC5 completely to get this effect.

They already knew that CXXC5 interacts with Dishevelled (DVL) and suppresses Wnt signaling through this interaction. So instead of deleting the entire gene, they used a blocking peptide, PTD-DBMP, to interfere specifically with the CXXC5–DVL interaction.

Again, blocking this interaction increased β-catenin signaling and increased the number of proliferating and hypertrophic chondrocytes in the growth plate.

At this point, the idea was becoming much more interesting:

CXXC5 ↑ → Wnt signaling ↓ → growth-plate activity ↓

while interfering with CXXC5 gave them the opposite direction.

But a peptide or a complete gene knockout isn't exactly the same thing as having a small molecule that could be used experimentally.

So the researchers went looking for one.

They screened 2,280 compounds for molecules capable of interfering with the CXXC5–DVL interaction. This eventually led them to indirubin-based compounds and, from there, to the compound we're interested in:

KY-19382. (our goat)

But finding a compound that works in a screening assay isn't enough. They needed to test whether KY actually affected both of the targets they were interested in.

First, they tested the CXXC5DVL interaction directly. KY-19382 inhibited this interaction with an IC₅₀ of approximately 19 nM.

They then tested GSK3β kinase activity separately. KY-19382 inhibited GSK3β with an IC₅₀ of approximately 10 nM.

The next question was whether those two effects actually translated into increased Wnt/β-catenin signaling inside cells.

For that, they used the TOPFlash reporter assay, which is commonly used to measure β-catenin/TCF-dependent transcription. Increasing concentrations of KY-19382 increased TOPFlash activity, showing that the compound was activating Wnt/β-catenin signaling in the cells.

They then went a step further and looked at what was happening to the proteins themselves.

In ATDC5 chondrocytes, KY-19382 increased β-catenin while reducing the active forms of GSK3α/β. They also performed an immunoprecipitation experiment to directly examine the CXXC5–DVL interaction. After KY treatment, the interaction was reduced.

And finally, they looked at where the β-catenin was going.

After treatment with KY-19382, substantially more β-catenin was detected in the nucleus of the chondrocytes.

So what happens when they put KY-19382 into mice?​

Now that they had shown that KY-19382 could activate Wnt/β-catenin signaling in cells, the researchers wanted to see whether the same thing happened in an actual growth plate.

They started with 7-week-old mice, which are already approaching the later stages of pubertal growth.

The mice received 0.1 mg/kg KY-19382 every day for 2 weeks. After treatment, the researchers examined the tibial growth plates and compared them with vehicle-treated controls.

The growth plate was larger in the KY-treated animals.

But they didn't just measure its overall size. They also looked at what the cells inside the growth plate were actually doing.

They used BrdU staining to identify proliferating cells and RUNX2 as a marker associated with hypertrophic differentiation. Both were increased after KY-19382 treatment.

They also looked at β-catenin itself.

And this was especially clear: nuclear β-catenin was strongly increased in the growth-plate chondrocytes.

So the change in growth-plate size came together with molecular and cellular changes that fit with increased Wnt/β-catenin activity.

They then repeated the experiment in 3-week-old mice, which are still undergoing rapid growth.

Again, the animals received 0.1 mg/kg KY-19382 daily for 2 weeks.

This time, the total growth-plate height increased, as did the heights of its individual zones. The number of BrdU-positive cells also increased, showing that more chondrocytes were actively proliferating.

But there was another question they needed to rule out.

If the hypertrophic zone becomes larger, that doesn't automatically mean the growth plate is producing more cells. It could also happen if the cartilage is simply being removed more slowly at the cartilage-to-bone interface.

So they looked at TRAP-positive foci, which mark osteoclast activity at this interface.

In the young mice, there was no significant difference in TRAP-positive foci between the KY-treated and control groups.

That makes a simple explanation based on reduced cartilage resorption less convincing.

Interestingly, the result was different in the older 7-week-old animals: KY-19382 increased TRAP-positive foci. The researchers interpreted this as evidence that KY was not merely accumulating cartilage in the growth plate, but was actually promoting the overall maturation process.

So by this point, the picture was becoming much more concrete.

And then they measured the bone itself​

The short-term experiments had shown that KY-19382 could make the growth plate more active. But the researchers wanted to know whether that effect was large enough to change the final length of the bone.

So they designed a much longer experiment.

They started with 3-week-old male C57BL/6 mice and treated them with 0.1 mg/kg KY-19382 by intraperitoneal injection every day for 10 weeks. The control animals received the vehicle instead.

This means the mice were followed from roughly 3 weeks of age to 13 weeks of age, covering a substantial part of the period in which their longitudinal growth normally slows down.

After the 10 weeks, the researchers took radiographs and measured the tibiae.

And this time, the result wasn't just a change in a staining pattern or in the appearance of the growth plate.

The KY-19382-treated mice had significantly longer tibiae than the vehicle-treated mice.

The reported difference was statistically significant, with P < 0.0005.

That gives the study an important progression:

There is, however, an important distinction here.

This experiment demonstrates the effect of KY-19382 as a compound. It does not prove that the increase in tibial length came exclusively from CXXC5 inhibition, because KY-19382 also inhibits GSK3β. (We dgaf about this tho)

The earlier Cxxc5 knockout experiments are therefore important for the CXXC5-specific part of the story, while the KY experiments show what happens when both of these mechanisms are affected by the compound.

The researchers also looked for obvious signs of toxicity during the long-term treatment. They reported no significant difference in body weight and found no histological abnormalities in the examined articular cartilage or liver.

That is reassuring within the limits of this particular experiment, but it doesn't turn KY-19382 into a proven safe compound. These were still preclinical mouse experiments, using a compound that has not been established as a human treatment.

At this point, the researchers had shown something quite substantial in mice:

CXXC5 is associated with the loss of growth-plate activity during maturation, removing or interfering with CXXC5 preserves Wnt/β-catenin signaling, and pharmacological activation with KY-19382 was associated with increased growth-plate activity and, after prolonged treatment, increased tibial length.

But the researchers still had another piece of the puzzle to address:

Why does CXXC5 increase during puberty in the first place?

That brings us back to estrogen.

The researchers then asked whether estrogen could be the signal driving this increase in CXXC5 during puberty.

They treated human chondrocytes with 17β-estradiol (E2) and found that CXXC5 expression increased after estrogen exposure, while β-catenin levels decreased. So the relationship seen during puberty could also be reproduced experimentally: more estrogen, more CXXC5, less active Wnt/β-catenin signaling.

They then looked at what this actually meant for the growth plate. When tibial growth plate cultures were treated with E2, longitudinal growth was reduced, together with reductions in the proliferative and hypertrophic zones. In other words, estrogen was not simply changing CXXC5 expression in isolation. It was associated with the structural changes that accompany growth plate senescence.

The strongest evidence came from the Cxxc5 knockout mice. When estrogen was given to normal mice, the growth plate developed the expected senescent changes. But when the same experiment was performed in mice lacking Cxxc5, most of that estrogen-induced phenotype was lost.

That places CXXC5 downstream of estrogen in this model. The study therefore supports a mechanism in which the rise in estrogen during puberty increases CXXC5, CXXC5 suppresses Wnt/β-catenin signaling, and the resulting reduction in chondrocyte activity contributes to growth plate senescence.

And that gives the whole study a much more complete chain:

Instead of simply adding a growth-promoting signal from outside, the compound interferes with one of the mechanisms that normally suppresses Wnt signaling. It blocks the CXXC5–DVL interaction while also inhibiting GSK3β, giving β-catenin two routes to remain active.

So the paper is essentially connecting two levels of the problem: the developmental signal that increases CXXC5 during puberty, and the molecular machinery through which CXXC5 reduces Wnt activity in the growth plate. The experiments with KY-19382 then ask whether interfering with that machinery is enough to preserve growth plate activity and extend longitudinal bone growth.

In the mouse experiments, the answer was yes: the growth plate remained more active, chondrocyte proliferation and maturation were increased, and prolonged treatment produced measurable increases in tibial length.

So what does the mouse dose mean in humans?​

The researchers used KY-19382 at 0.1 mg/kg once daily in the mouse experiments. The short-term studies lasted 2 weeks, while the long-term experiment treated the mice daily for 10 weeks, from 3 to 13 weeks of age.

A common preclinical approach is to use body-surface-area scaling, which gives a rough human-equivalent dose (HED).

For mice, the standard Km factor is 3, compared with 37 for an adult human:

HED = animal dose × (mouse Km / human Km)

So for the dose used in this study:

0.1 mg/kg × 3/37 ≈ 0.0081 mg/kg

That corresponds to roughly:

• 60 kg human → 0.49 mg/day
• 70 kg human → 0.57 mg/day
• 80 kg human → 0.65 mg/day

So, purely as a body-surface-area conversion, the 0.1 mg/kg mouse dose corresponds to about 0.5–0.65 mg in a 60–80 kg adult human.

Simple math duh .

Administration

I honestly CBA to make a guide on administration and lowkey want to go to sleep.

You have 2 choices:

1. Oral

Guide: Geometrically dilute the powder and put it in capsules (duh)
Note: You will need to account for a lower Bioavailibility

2. SubQ

Guide: Watch my friends video on TT on how to make a DIY solution:


Sources and Price:

Cost per Gram: Usually varies between 200$-600$

look on sites such as Echemi or Lookchem for good vendors.

If you can't find a source DM me.

I won't even correct my grammar I CBA Fuck all of you,

YES I USED AI TO FORMAT EVERYTHING NIGGER, IT'S 2026. Why would I not?



​

wow brooo gsmn!

 

[cookieslayer]

I’ve had 5g of KY stored in my freezer for months now and haven’t touched it once. Given that my main issue is hair loss wouldn’t applying it topically make the most sense? I’m still trying to figure out the best route to take rn

throw that bs bro get a new one