Sonic Hedgehog(Shh) & Wnt/β-Catenin Pathway Modulation: Topically Applied Hair Growth Agonists(NORWOODCELS GTFINH)

[Shirobon]

​

Desktop Site on mobile or zoom out Use Darkmode: Click Here ello, just thought it was kinda an interesting topic, and the name was kinda funny so enjoy reading ​

Spoiler: Thread Song:

Abstract:​

In the world of Hair morphogenesis and management, their are few real promising Pharmaceutical options out there, men are often limited to shitty Anti-androgens, or vasodilators like minoxidil which either stop working immediately after usage end or have side effects that make it annoying to use. In this guide i'll describe an interesting not very known method for hair growth that is topical and promising.​

Overview Hair Morphogenesis Sonic Hedgehog Pathway Importance Other Possible Therapies

Topical Formulations

Overview:​

​ The process of hair Follicle creation/Hair Morphogenesis is a complex multi-step development featuring 3 main steps, those being induction, organogenesis, and cytodifferentiation. These three main steps branch off into multiple stages for each step, as much as 8. But these are mostly only relevant during Embryogenesis, the hair follicle cycling however is incredibly important during all points in life, mainly being regulated by hormones such as Androgens(DHT, Testosterone, etc) and others. The Follicle Cycle is comprised of 3 stages; anagen(Growth) catagen(Transition), and Telogen(Cease), Telogen has another stage being Exogen(Shedding). During Embryogenesis, the process of Hair Follicle Creation is regulated by signaling pathways, these pathways are incredibly vital to the development of hair and if obstructed during development can cause diseases like Alopecia and Hair Structural Differentiation. Said pathways would be, WNT BMP EDAR and Sonic Hedgehog(Shh)​ ​ ☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲​ ☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲​ Disruptions in each of these pathways leads to a variety of results, effecting hair growth in abnormal ways leading researchers to speculate their purpose in Morphogenesis and hair remodeling/cycle during life, genes like WNT, WNT10b, LEF1, and EDAR when afflicted promote early morphogenesis of hair follicles. On the otherside of the spectrum, Genes like DKK4, BMP2, DKK1, BMP4, and BMP7 are thought to have connections to inhibiting premature morphogenesis.​ Sonic Hedgehog(Shh) is incredibly important to Embryonic and Postnatal Development, being one of the main regulators in hair follicle cycling, working to promote Anagen initiation from the Telogen Phase, meaning it plays a key role in the activation of hair growth. The process by which Shh functions to do this, goes as follows; Shh binds to Protein patched homolog 1(PTCH1) , PTCH1 subquestinally gets expressed, PTCH1 then releases Smoothend(SMO) Protein inhibition causing a Cascade that ultimately leads to the Anagen Transition. ​ ☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲​ 〣〣〣〣〣〣〣〣〣〣 〣 〣 〣 〣 〣 〣 〣 〣 〣 〣 〣 〣 〣 〣 〣 〣 〣 〣 〣 〣 〣 〣 〣 〣​ Mice that are afflicted with antibodies that are specialized to attack Shh related proteins were observed to have notable damage to hair follicles, and more importantly in-turn caused hair loss. As a result of that study, the consensus that possible Shh related therapies for Hair growth were explored, Modulation of proteins connected to the Shh pathway were found to have a real effect on promoting hair-growth. SMO Agonists being the main realm of modulation explored.​ Most SMO Agonists have purposes outside of Therapies For hair Regrowth, a few were studied for this use and with differentiating levels of success, The most promising being Oxy133, Hh-Ag 1.5, and SAG SMO Agonists:​ Oxy133:​ Hh-Ag 1.5:​ Oxy133 and Hh-Ag 1.5 are the best options with the Highest safety profiles, Oxy133 is a derivative of other Oxysterol like Resveratrol, and Oxyreversatrol. Both found to have indirect effects on Shh and Wnt/ beta-catenin signaling, Oxy133 albeit theoretical on its influence provides a noteworthy play in Topical hair growth, Hh-Ag 1.5 However has Clinical Evidence; In Animal studies, Hh-Ag 1.5 increased hair follicle growth in mouse depilated skin. Human ex vivo studies, it showed increased levels of Shh activity and growth. SAG is likely the best option for availability and potency, being a direct agonist of the Smoothend Protein, that's also been tested topically for this very purpose with success, but unfortunately carries more risk. (imo just get SAG its way cheaper just dont be dumb) ​ WNT/β-catenin Activators:​ Aside from the Novel SMO agonists, WNT activators show promise aswell, WNT plays an extremely similar role to Shh in Hair Follicle Cycling, both regulating Anagen Transition and growth periods. A combination usage of WNT and Shh Topicals could easily outperform anything we have commercially as of now. Some Known WNT Activators that are notable would be; ALRV5XR, and KY19382, There are others but currently these show the most promise. ​ ALRV5XR:​ KY19382:​ Proprietary Product​ ALRV5XR is a botanical formulation of Extracts and vitamins Administered Orally or Topically, it has been hypothesized to activate WNT along with a multitude of other pathways to stimulate hair growth, ALRV5XR is commercial so you can actually buy this instead of needing to formulate yourself, and studies have shown it is more effective than Minoxidil in AGA related hairloss and typical. KY19382 is an incredibly potent WNT Activator that functions through GSK3β inhibition along with a few other pathways, While it is preclinical, animal and human ex vivo studies Promote the idea that Ky19382 stimulated anagen transition, and hair regrowth, both of these counteracted Androgenic Alopecia in models and KY19382 mechanistically is the most promising even though its preclinical. ​

Topical Formulations:​

​ SMO Agonists:​ Topical SAG Formulation:​ Topical Hh-Ag 1.5 Formulation:​ ☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲​ ☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲ ​ 100 mL Batch(200 day supply max)​ Ingredients:​ Concentrations:​ 〣 SAG 4.90 µg(micro)​ 〣 Dimethyl Sulfoxide(DMSO) 5.0 mL​ 〣 Propylene Glycol 20.0 mL​ 〣 Isopropyl Myristate 5.0 mL​ 〣 Ethanol 70mL(q.s to 100 mL)​ 〣 ​ Basically no Full formulations for Sag Base, required for me to shittly create one use with caution boyos, SAG Formulation has to be precise since above a certain threshold Inhibitory effects are observed. Li, Shao-Ting. “Hes1 Regulates Anagen Initiation and Hair Follicle Regeneration through Modulation of Hedgehog Signaling - Suen - 2020 - Stem Cells - Wiley Online Library.” Stem Cells Journals, 13 Nov. 2019, stemcellsjournals.onlinelibrary.wiley.com/doi/full/10.1002/stem.3117.​ ​ 100 mL Batch(200 day supply max)​ Ingredients:​ Concentrations:​ 〣 Hh-Ag1.5 5.260 µg(micro)​ 〣 Ethoxydiglycol 10.0 mL​ 〣 Dimethyl Isosorbide 5.0 mL​ 〣 Ethanol 85.0 mL​ 〣 ​ Less data than Free base SAG, Again Proceed with Caution Li, Shao-Ting. “Hes1 Regulates Anagen Initiation and Hair Follicle Regeneration through Modulation of Hedgehog Signaling - Suen - 2020 - Stem Cells - Wiley Online Library.” Stem Cells Journals, 13 Nov. 2019, stemcellsjournals.onlinelibrary.wiley.com/doi/full/10.1002/stem.3117.​

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WNT Activators:​

ALRV5XR Sourcing:​ Topical KY19382 Formulation:​ ☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲​ ☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲ ​ Source Listings are labeled under Brand Name Replenology​ Sourcing:​ Arbor Life Labs 〣 Replenology 〣 HPIHAIR Partners 〣 LAPEARL Beauty 〣 ​ ALRV5XR can be sometimes expensive, view all sources to find which is the cheapest currently, Very safe product Feldman, Peter R. “Safety and Efficacy of ALRV5XR in Men with Androgenetic Alopecia: A Randomised, Double-Blinded, Placebo-Controlled Clinical Trial - Eclinicalmedicine.” The Lancet, Oct. 2021, www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00404-1/fulltext.​ ​ 100 mL Batch(200 day supply max)​ Ingredients:​ Concentrations:​ 〣 KY19382 18.01 mg​ 〣 PEG400 90.0 mL​ 〣 Tween 80 5.0 mL​ 〣 Dimethyl Sulfoxide(DMSO) 5.0 mL​ 〣 ​ This is likely to give you the most ROI out of every compound listed, its cheap, and well documented, but still proceed with caution, Formulation untested. Ryu, Yeong Chan, et al. “KY19382, a Novel Activator of Wnt/β-Catenin Signalling, Promotes Hair Regrowth and Hair Follicle Neogenesis.” British Journal of Pharmacology, U.S. National Library of Medicine, June 2021, pmc.ncbi.nlm.nih.gov/articles/PMC8251890/.​

Conclusion:​

Shh modulators and WNT Activators are interesting new experimental therapies for hair growth, that with time will likely replace minoxidil and hopefully DHT Blockers. Studies Showing rapid hair growth as a topical agent, and other benefits aswell. But they still have currently some risks since Shh is such a central pathway in numerous processes that if Shh is interfered with possibly could have effects like oncogenesis, WNT Topicals however will likely give you more ROI currently if your low inhib try it out ​

Spoiler: Tags:

@shedontluv-U @Askinov @Stalker @Sayori @filthycurrycel @Regret @sayonara @Vrilltrum

 

[peptidehater22]

high effort, gt200 and wnt upregulators are basically the future

 

[Shirobon]

high effort, but gt200 and wnt upregulators are basically the future

wnt is discussed in this thread

 

[peptidehater22]

wnt is discussed in this thread

yes i saw lol

 

[Shirobon]

yes i saw lol

o ok

 

[thurzdx]

​

Desktop Site on mobile or zoom out Use Darkmode: Click Here ello, just thought it was kinda an interesting topic, and the name was kinda funny so enjoy reading ​

Spoiler: Thread Song:

Abstract:​

In the world of Hair morphogenesis and management, their are few real promising Pharmaceutical options out there, men are often limited to shitty Anti-androgens, or vasodilators like minoxidil which either stop working immediately after usage end or have side effects that make it annoying to use. In this guide i'll describe an interesting not very known method for hair growth that is topical and promising.​

Overview Hair Morphogenesis Sonic Hedgehog Pathway Importance Other Possible Therapies

Topical Formulations

Overview:​

​ The process of hair Follicle creation/Hair Morphogenesis is a complex multi-step development featuring 3 main steps, those being induction, organogenesis, and cytodifferentiation. These three main steps branch off into multiple stages for each step, as much as 8. But these are mostly only relevant during Embryogenesis, the hair follicle cycling however is incredibly important during all points in life, mainly being regulated by hormones such as Androgens(DHT, Testosterone, etc) and others. The Follicle Cycle is comprised of 3 stages; anagen(Growth) catagen(Transition), and Telogen(Cease), Telogen has another stage being Exogen(Shedding). During Embryogenesis, the process of Hair Follicle Creation is regulated by signaling pathways, these pathways are incredibly vital to the development of hair and if obstructed during development can cause diseases like Alopecia and Hair Structural Differentiation. Said pathways would be, WNT BMP EDAR and Sonic Hedgehog(Shh)​ ​ ☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲​ ☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲​ Disruptions in each of these pathways leads to a variety of results, effecting hair growth in abnormal ways leading researchers to speculate their purpose in Morphogenesis and hair remodeling/cycle during life, genes like WNT, WNT10b, LEF1, and EDAR when afflicted promote early morphogenesis of hair follicles. On the otherside of the spectrum, Genes like DKK4, BMP2, DKK1, BMP4, and BMP7 are thought to have connections to inhibiting premature morphogenesis.​ Sonic Hedgehog(Shh) is incredibly important to Embryonic and Postnatal Development, being one of the main regulators in hair follicle cycling, working to promote Anagen initiation from the Telogen Phase, meaning it plays a key role in the activation of hair growth. The process by which Shh functions to do this, goes as follows; Shh binds to Protein patched homolog 1(PTCH1) , PTCH1 subquestinally gets expressed, PTCH1 then releases Smoothend(SMO) Protein inhibition causing a Cascade that ultimately leads to the Anagen Transition. ​ ☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲​ 〣〣〣〣〣〣〣〣〣〣 〣 〣 〣 〣 〣 〣 〣 〣 〣 〣 〣 〣 〣 〣 〣 〣 〣 〣 〣 〣 〣 〣 〣 〣​ Mice that are afflicted with antibodies that are specialized to attack Shh related proteins were observed to have notable damage to hair follicles, and more importantly in-turn caused hair loss. As a result of that study, the consensus that possible Shh related therapies for Hair growth were explored, Modulation of proteins connected to the Shh pathway were found to have a real effect on promoting hair-growth. SMO Agonists being the main realm of modulation explored.​ Most SMO Agonists have purposes outside of Therapies For hair Regrowth, a few were studied for this use and with differentiating levels of success, The most promising being Oxy133, Hh-Ag 1.5, and SAG SMO Agonists:​ Oxy133:​ Hh-Ag 1.5:​ Oxy133 and Hh-Ag 1.5 are the best options with the Highest safety profiles, Oxy133 is a derivative of other Oxysterol like Resveratrol, and Oxyreversatrol. Both found to have indirect effects on Shh and Wnt/ beta-catenin signaling, Oxy133 albeit theoretical on its influence provides a noteworthy play in Topical hair growth, Hh-Ag 1.5 However has Clinical Evidence; In Animal studies, Hh-Ag 1.5 increased hair follicle growth in mouse depilated skin. Human ex vivo studies, it showed increased levels of Shh activity and growth. SAG is likely the best option for availability and potency, being a direct agonist of the Smoothend Protein, that's also been tested topically for this very purpose with success, but unfortunately carries more risk. (imo just get SAG its way cheaper just dont be dumb)​ WNT/β-catenin Activators:​ Aside from the Novel SMO agonists, WNT activators show promise aswell, WNT plays an extremely similar role to Shh in Hair Follicle Cycling, both regulating Anagen Transition and growth periods. A combination usage of WNT and Shh Topicals could easily outperform anything we have commercially as of now. Some Known WNT Activators that are notable would be; ALRV5XR, and KY19382, There are others but currently these show the most promise.​ ALRV5XR:​ KY19382:​ Proprietary Product​ ALRV5XR is a botanical formulation of Extracts and vitamins Administered Orally or Topically, it has been hypothesized to activate WNT along with a multitude of other pathways to stimulate hair growth, ALRV5XR is commercial so you can actually buy this instead of needing to formulate yourself, and studies have shown it is more effective than Minoxidil in AGA related hairloss and typical. KY19382 is an incredibly potent WNT Activator that functions through GSK3β inhibition along with a few other pathways, While it is preclinical, animal and human ex vivo studies Promote the idea that Ky19382 stimulated anagen transition, and hair regrowth, both of these counteracted Androgenic Alopecia in models and KY19382 mechanistically is the most promising even though its preclinical.​

Topical Formulations:​

​ SMO Agonists:​ Topical SAG Formulation:​ Topical Hh-Ag 1.5 Formulation:​ ☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲​ ☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲ ​ 100 mL Batch(200 day supply max)​ Ingredients:​ Concentrations:​ 〣 SAG 4.90 µg(micro)​ 〣 Dimethyl Sulfoxide(DMSO) 5.0 mL​ 〣 Propylene Glycol 20.0 mL​ 〣 Isopropyl Myristate 5.0 mL​ 〣 Ethanol 70mL(q.s to 100 mL)​ 〣 ​ Basically no Full formulations for Sag Base, required for me to shittly create one use with caution boyos, SAG Formulation has to be precise since above a certain threshold Inhibitory effects are observed. Li, Shao-Ting. “Hes1 Regulates Anagen Initiation and Hair Follicle Regeneration through Modulation of Hedgehog Signaling - Suen - 2020 - Stem Cells - Wiley Online Library.” Stem Cells Journals, 13 Nov. 2019, stemcellsjournals.onlinelibrary.wiley.com/doi/full/10.1002/stem.3117.​ ​ 100 mL Batch(200 day supply max)​ Ingredients:​ Concentrations:​ 〣 Hh-Ag1.5 5.260 µg(micro)​ 〣 Ethoxydiglycol 10.0 mL​ 〣 Dimethyl Isosorbide 5.0 mL​ 〣 Ethanol 85.0 mL​ 〣 ​ Less data than Free base SAG, Again Proceed with Caution Li, Shao-Ting. “Hes1 Regulates Anagen Initiation and Hair Follicle Regeneration through Modulation of Hedgehog Signaling - Suen - 2020 - Stem Cells - Wiley Online Library.” Stem Cells Journals, 13 Nov. 2019, stemcellsjournals.onlinelibrary.wiley.com/doi/full/10.1002/stem.3117.​

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N ​

ALRV5XR Sourcing:​ Topical KY19382 Formulation:​ ☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲​ ☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲☲ ​ Source Listings are labeled under Brand Name Replenology​ Sourcing:​ Arbor Life Labs 〣 Replenology 〣 HPIHAIR Partners 〣 LAPEARL Beauty 〣 ​ ALRV5XR can be sometimes expensive, view all sources to find which is the cheapest currently, Very safe product Feldman, Peter R. “Safety and Efficacy of ALRV5XR in Men with Androgenetic Alopecia: A Randomised, Double-Blinded, Placebo-Controlled Clinical Trial - Eclinicalmedicine.” The Lancet, Oct. 2021, www.thelancet.com/journals/eclinm/article/PIIS2589-5370(21)00404-1/fulltext.​ ​ 100 mL Batch(200 day supply max)​ Ingredients:​ Concentrations:​ 〣 KY19382 18.01 mg​ 〣 PEG400 90.0 mL​ 〣 Tween 80 5.0 mL​ 〣 Dimethyl Sulfoxide(DMSO) 5.0 mL​ 〣 ​ This is likely to give you the most ROI out of every compound listed, its cheap, and well documented, but still proceed with caution, Formulation untested. Ryu, Yeong Chan, et al. “KY19382, a Novel Activator of Wnt/β-Catenin Signalling, Promotes Hair Regrowth and Hair Follicle Neogenesis.” British Journal of Pharmacology, U.S. National Library of Medicine, June 2021, pmc.ncbi.nlm.nih.gov/articles/PMC8251890/.​

Conclusion:​

Shh modulators and WNT Activators are interesting new experimental therapies for hair growth, that with time will likely replace minoxidil and hopefully DHT Blockers. Studies Showing rapid hair growth as a topical agent, and other benefits aswell. But they still have currently some risks since Shh is such a central pathway in numerous processes that if Shh is interfered with possibly could have effects like oncogenesis, WNT Topicals however will likely give you more ROI currently if your low inhib try it out ​

Spoiler: Tags:

@shedontluv-U @Askinov @Stalker @Sayori @filthycurrycel @Regret @sayonara @Vrilltrum

I like the formatting, I'll read it when I can

 

[Shirobon]

I like the formatting, I'll read it when I can

thxx


formatting wacky on mobile sadly

 

[thurzdx]

thxx


formatting wacky on mobile sadly

I read it on PC, so it doesn't really matter. thread look really nice

 

[Shirobon]

I read it on PC, so it doesn't really matter. thread look really nice