FGFR3 OR A DEFORMITY GENE

[JOTAROSON]

FGFR3 and its inhibitors

FGFR3 is a transmembrane protein that acts as a highly specific receptor on the cell surface. As a critical component of the cellular signalling system, it plays a central role in regulating fundamental biological processes such as cell proliferation, differentiation, migration and survival.

Spoiler: Sphere of influence

The primary function of FGFR3 is to regulate growth and development. This receptor is best known for its crucial role in controlling bone growth. In particular, FGFR3 acts as a key negative regulator of longitudinal bone growth by influencing the activity of chondrocytes in the skeletal growth plates

IN OTHER WORDS, IT CAUSES ACHONDROPLASIA, A RECEDING JAWLINE, POOR BODY PROPORTIONS, AND SO ON




INHIBITORS



1)HGH - Forceful suppression
The first and most tried-and-tested method is to ‘flood’ the system with doses of GH in order to override the receptor’s resistance.
hGH stimulates proliferation via IGF-1, counteracting the signals from FGFR3.

Spoiler: RESEARCH

In a study of children with growth disorders (achondroplasia), a daily dose of 1 IU/kg per week resulted in a phenomenal increase. Growth rates jumped from a meagre 3.2 cm to an impressive 8.3 cm per year.

Growth and growth hormone therapy in children with achondroplasia: a two-year experience - PubMed

The efficacy and safety of recombinant human growth hormone (hGH) administration was studied in children with achondroplasia. Fifteen children with achondroplasia, seven boys (4.8-12.2 years of age) and 12 girls (5.7-2.2 years of age), were treated daily with hGH at a dosage of 1 IU/kg/week...

pubmed.ncbi.nlm.nih.gov

THE MAIN NUANCE
HGH does not switch off FGFR3; it simply overpowers the receptor’s inhibitory system



2)ASP5878 - An oral receptor inhibitor
ASP5878 is a selective inhibitor of FGFR tyrosine kinase. It was originally developed to treat tumours, but has proved to be a goldmine for growth.

Unlike its injectable counterparts, this drug is taken orally (in tablet form).

Spoiler: RESEARCH

A dose of 300 μg/kg resulted in significant bone elongation in the models.
A positive trade-off between the therapeutic dose and side effects (minimal effect on the corneal epithelium)

Evaluation of FGFR inhibitor ASP5878 as a drug candidate for achondroplasia - PubMed

Achondroplasia is caused by gain-of-function mutations in FGFR3 gene and leads to short-limb dwarfism. A stabilized analogue of C-type natriuretic peptide (CNP) is known to elongate bone by interacting with FGFR3 signals and thus is a promising drug candidate. However, it needs daily...

pubmed.ncbi.nlm.nih.gov

makes it an extremely promising option for those who don’t want to have their skin pierced every day.


3)TYRA300 - It is an innovative selective FGFR3 inhibitor that acts like a molecular sniper.

Spoiler: RESEARCH

Experiments have shown not only an increase in the length of long bones (thighs, lower legs), but also an increase in naso-anal length (overall height).
Skull and spine: The preparation addresses a critical issue — stenosis of the foramen magnum. It widens and corrects the shape of the skull, as well as increasing the length of the lumbar vertebrae.

TYRA-300, an FGFR3-selective inhibitor, promotes bone growth in two FGFR3-driven models of chondrodysplasia - PubMed

Achondroplasia (ACH) and hypochondroplasia (HCH), the two most common types of dwarfism, are each caused by FGFR3 gain-of-function mutations that result in increased FGFR3 signaling, which disrupts chondrogenesis and osteogenesis, resulting in disproportionately shortened long bones. In this...

pubmed.ncbi.nlm.nih.gov

RESULTS
FGFR3 is one of your genetic enemies. If your goal is to maximise height and achieve the right facial proportions, you cannot afford to ignore this receptor. The use of selective inhibitors (such as TYRA-300 or ASP5878)

 

[JOTAROSON]

:Анимация:FGFR3 и его ингибиторы:Анимация:

FGFR3 — это трансмембранный белок, который действует как высокоспецифичный рецептор на поверхности клетки. Являясь важнейшим компонентом клеточной сигнальной системы, он играет центральную роль в регулировании фундаментальных биологических процессов, таких как пролиферация, дифференциация, миграция и выживание клеток.

View attachment 4800612

Spoiler: Сфера влияния

Основная функция FGFR3 — регуляция роста и развития. Этот рецептор наиболее известен своей решающей ролью в контроле роста костей. В частности, FGFR3 действует как ключевой негативный регулятор продольного роста костей, влияя на активность хондроцитов в зонах роста скелета.
[/СПОЙЛЕР]


Иными словами, это вызывает ахондроплазию, смещение челюсти назад, нарушение пропорций тела и так далее.




:ВНИМАНИЕ:ИНГИБИТОРЫ:ВНИМАНИЕ:



1) Гормон роста (HGH) - Сильное подавление
Первый и наиболее проверенный метод заключается в том, чтобы «насытить» систему дозами гормона роста (ГР), чтобы преодолеть резистентность рецептора.
Гормон роста человека (hGH) стимулирует пролиферацию через IGF-1, противодействуя сигналам от FGFR3.

View attachment 4800633

Spoiler: RESEARCH

В исследовании детей с нарушениями роста (ахондроплазией) ежедневная доза 1 МЕ/кг в неделю привела к феноменальному увеличению роста. Темпы роста подскочили с незначительных 3,2 см до впечатляющих 8,3 см в год.

Growth and growth hormone therapy in children with achondroplasia: a two-year experience - PubMed

The efficacy and safety of recombinant human growth hormone (hGH) administration was studied in children with achondroplasia. Fifteen children with achondroplasia, seven boys (4.8-12.2 years of age) and 12 girls (5.7-2.2 years of age), were treated daily with hGH at a dosage of 1 IU/kg/week...

pubmed.ncbi.nlm.nih.gov

[/СПОЙЛЕР]

:ВНИМАНИЕ:ГЛАВНЫЙ НЮАНС:ВНИМАНИЕ:
:Неуклюжий:Гормон роста (HGH) не отключает FGFR3; он просто подавляет ингибиторную систему рецептора.:Неуклюжий:



2) ASP5878 — пероральный ингибитор рецепторов
ASP5878 — это селективный ингибитор тирозин-киназы FGFR. Первоначально он был разработан для лечения опухолей, но оказался настоящим кладезем средств для борьбы с их ростом.

В отличие от инъекционных аналогов, этот препарат принимается внутрь (в форме таблеток).

View attachment 4800650

Spoiler: RESEARCH

Доза 300 мкг/кг привела к значительному удлинению костей в исследуемых моделях.
Положительный компромисс между терапевтической дозой и побочными эффектами (минимальное воздействие на эпителий роговицы).

Evaluation of FGFR inhibitor ASP5878 as a drug candidate for achondroplasia - PubMed

Achondroplasia is caused by gain-of-function mutations in FGFR3 gene and leads to short-limb dwarfism. A stabilized analogue of C-type natriuretic peptide (CNP) is known to elongate bone by interacting with FGFR3 signals and thus is a promising drug candidate. However, it needs daily...

pubmed.ncbi.nlm.nih.gov

[/СПОЙЛЕР]

Это делает его чрезвычайно перспективным вариантом для тех, кто не хочет прокалывать кожу каждый день.


3) TYRA300 — это инновационный селективный ингибитор FGFR3, действующий подобно молекулярному снайперу.


View attachment 4800637

Spoiler: RESEARCH

Эксперименты показали не только увеличение длины длинных костей (бедер, голеней), но и увеличение носо-анальной длины (общего роста).
Череп и позвоночник: Эта процедура направлена на решение критически важной проблемы — стеноза большого затылочного отверстия. Она расширяет и корректирует форму черепа, а также увеличивает длину поясничных позвонков.

TYRA-300, an FGFR3-selective inhibitor, promotes bone growth in two FGFR3-driven models of chondrodysplasia - PubMed

Achondroplasia (ACH) and hypochondroplasia (HCH), the two most common types of dwarfism, are each caused by FGFR3 gain-of-function mutations that result in increased FGFR3 signaling, which disrupts chondrogenesis and osteogenesis, resulting in disproportionately shortened long bones. In this...

pubmed.ncbi.nlm.nih.gov

[/СПОЙЛЕР]


:Тревога: РЕЗУЛЬТАТЫ:Тревога:
FGFR3 — один из ваших генетических врагов. Если ваша цель — максимально увеличить рост и добиться правильных пропорций лица, вы не можете позволить себе игнорировать этот рецептор. Использование селективных ингибиторов (таких как TYRA-300 или ASP5878) может помочь.

Spoiler: Сфера влияния

Spoiler: RESEARCH

Spoiler: RESEARCH

Spoiler: RESEARCH

Please let me know if you would like to analyze any other gene.

 

[JOTAROSON]

:Анимация:FGFR3 и его ингибиторы:Анимация:

FGFR3 — это трансмембранный белок, который действует как высокоспецифичный рецептор на поверхности клетки. Являясь важнейшим компонентом клеточной сигнальной системы, он играет центральную роль в регулировании фундаментальных биологических процессов, таких как пролиферация, дифференциация, миграция и выживание клеток.

View attachment 4800612

Spoiler: Сфера влияния

Основная функция FGFR3 — регуляция роста и развития. Этот рецептор наиболее известен своей решающей ролью в контроле роста костей. В частности, FGFR3 действует как ключевой негативный регулятор продольного роста костей, влияя на активность хондроцитов в зонах роста скелета.
[/СПОЙЛЕР]


Иными словами, это вызывает ахондроплазию, смещение челюсти назад, нарушение пропорций тела и так далее.




:ВНИМАНИЕ:ИНГИБИТОРЫ:ВНИМАНИЕ:



1) Гормон роста (HGH) - Сильное подавление
Первый и наиболее проверенный метод заключается в том, чтобы «насытить» систему дозами гормона роста (ГР), чтобы преодолеть резистентность рецептора.
Гормон роста человека (hGH) стимулирует пролиферацию через IGF-1, противодействуя сигналам от FGFR3.

View attachment 4800633

Spoiler: RESEARCH

В исследовании детей с нарушениями роста (ахондроплазией) ежедневная доза 1 МЕ/кг в неделю привела к феноменальному увеличению роста. Темпы роста подскочили с незначительных 3,2 см до впечатляющих 8,3 см в год.

Growth and growth hormone therapy in children with achondroplasia: a two-year experience - PubMed

The efficacy and safety of recombinant human growth hormone (hGH) administration was studied in children with achondroplasia. Fifteen children with achondroplasia, seven boys (4.8-12.2 years of age) and 12 girls (5.7-2.2 years of age), were treated daily with hGH at a dosage of 1 IU/kg/week...

pubmed.ncbi.nlm.nih.gov

[/СПОЙЛЕР]

:ВНИМАНИЕ:ГЛАВНЫЙ НЮАНС:ВНИМАНИЕ:
:Неуклюжий:Гормон роста (HGH) не отключает FGFR3; он просто подавляет ингибиторную систему рецептора.:Неуклюжий:



2) ASP5878 — пероральный ингибитор рецепторов
ASP5878 — это селективный ингибитор тирозин-киназы FGFR. Первоначально он был разработан для лечения опухолей, но оказался настоящим кладезем средств для борьбы с их ростом.

В отличие от инъекционных аналогов, этот препарат принимается внутрь (в форме таблеток).

View attachment 4800650

Spoiler: RESEARCH

Доза 300 мкг/кг привела к значительному удлинению костей в исследуемых моделях.
Положительный компромисс между терапевтической дозой и побочными эффектами (минимальное воздействие на эпителий роговицы).

Evaluation of FGFR inhibitor ASP5878 as a drug candidate for achondroplasia - PubMed

Achondroplasia is caused by gain-of-function mutations in FGFR3 gene and leads to short-limb dwarfism. A stabilized analogue of C-type natriuretic peptide (CNP) is known to elongate bone by interacting with FGFR3 signals and thus is a promising drug candidate. However, it needs daily...

pubmed.ncbi.nlm.nih.gov

[/СПОЙЛЕР]

Это делает его чрезвычайно перспективным вариантом для тех, кто не хочет прокалывать кожу каждый день.


3) TYRA300 — это инновационный селективный ингибитор FGFR3, действующий подобно молекулярному снайперу.


View attachment 4800637

Spoiler: RESEARCH

Эксперименты показали не только увеличение длины длинных костей (бедер, голеней), но и увеличение носо-анальной длины (общего роста).
Череп и позвоночник: Эта процедура направлена на решение критически важной проблемы — стеноза большого затылочного отверстия. Она расширяет и корректирует форму черепа, а также увеличивает длину поясничных позвонков.

TYRA-300, an FGFR3-selective inhibitor, promotes bone growth in two FGFR3-driven models of chondrodysplasia - PubMed

Achondroplasia (ACH) and hypochondroplasia (HCH), the two most common types of dwarfism, are each caused by FGFR3 gain-of-function mutations that result in increased FGFR3 signaling, which disrupts chondrogenesis and osteogenesis, resulting in disproportionately shortened long bones. In this...

pubmed.ncbi.nlm.nih.gov

[/СПОЙЛЕР]


:Тревога: РЕЗУЛЬТАТЫ:Тревога:
FGFR3 — один из ваших генетических врагов. Если ваша цель — максимально увеличить рост и добиться правильных пропорций лица, вы не можете позволить себе игнорировать этот рецептор. Использование селективных ингибиторов (таких как TYRA-300 или ASP5878) может помочь.

Spoiler: Сфера влияния

Spoiler: RESEARCH

Spoiler: RESEARCH

Spoiler: RESEARCH

@vi24v_

 

[JOTAROSON]

@vi24v_

 

[JOTAROSON]

@birthdefect @iblameocclusalcant @wearegettingtohtn @ilovedominos26
@Ahmed88 @Bryce

 

[JOTAROSON]

@birthdefect @iblameocclusalcant @wearegettingtohtn @ilovedominos26
@Ahmed88 @Bryce

НTell me what other gene or topic you would like to see.

 

[Jesus_ist_König]

@Zagro @Genio is this valid?

 

[wearegettingtohtn]

FGFR3 and its inhibitors

FGFR3 is a transmembrane protein that acts as a highly specific receptor on the cell surface. As a critical component of the cellular signalling system, it plays a central role in regulating fundamental biological processes such as cell proliferation, differentiation, migration and survival.

View attachment 4800612

Spoiler: Sphere of influence

The primary function of FGFR3 is to regulate growth and development. This receptor is best known for its crucial role in controlling bone growth. In particular, FGFR3 acts as a key negative regulator of longitudinal bone growth by influencing the activity of chondrocytes in the skeletal growth plates

IN OTHER WORDS, IT CAUSES ACHONDROPLASIA, A RECEDING JAWLINE, POOR BODY PROPORTIONS, AND SO ON




INHIBITORS



1)HGH - Forceful suppression
The first and most tried-and-tested method is to ‘flood’ the system with doses of GH in order to override the receptor’s resistance.
hGH stimulates proliferation via IGF-1, counteracting the signals from FGFR3.

View attachment 4800633

Spoiler: RESEARCH

In a study of children with growth disorders (achondroplasia), a daily dose of 1 IU/kg per week resulted in a phenomenal increase. Growth rates jumped from a meagre 3.2 cm to an impressive 8.3 cm per year.

Growth and growth hormone therapy in children with achondroplasia: a two-year experience - PubMed

The efficacy and safety of recombinant human growth hormone (hGH) administration was studied in children with achondroplasia. Fifteen children with achondroplasia, seven boys (4.8-12.2 years of age) and 12 girls (5.7-2.2 years of age), were treated daily with hGH at a dosage of 1 IU/kg/week...

pubmed.ncbi.nlm.nih.gov

THE MAIN NUANCE
HGH does not switch off FGFR3; it simply overpowers the receptor’s inhibitory system



2)ASP5878 - An oral receptor inhibitor
ASP5878 is a selective inhibitor of FGFR tyrosine kinase. It was originally developed to treat tumours, but has proved to be a goldmine for growth.

Unlike its injectable counterparts, this drug is taken orally (in tablet form).

View attachment 4800650

Spoiler: RESEARCH

A dose of 300 μg/kg resulted in significant bone elongation in the models.
A positive trade-off between the therapeutic dose and side effects (minimal effect on the corneal epithelium)

Evaluation of FGFR inhibitor ASP5878 as a drug candidate for achondroplasia - PubMed

Achondroplasia is caused by gain-of-function mutations in FGFR3 gene and leads to short-limb dwarfism. A stabilized analogue of C-type natriuretic peptide (CNP) is known to elongate bone by interacting with FGFR3 signals and thus is a promising drug candidate. However, it needs daily...

pubmed.ncbi.nlm.nih.gov

makes it an extremely promising option for those who don’t want to have their skin pierced every day.


3)TYRA300 - It is an innovative selective FGFR3 inhibitor that acts like a molecular sniper.


View attachment 4800637

Spoiler: RESEARCH

Experiments have shown not only an increase in the length of long bones (thighs, lower legs), but also an increase in naso-anal length (overall height).
Skull and spine: The preparation addresses a critical issue — stenosis of the foramen magnum. It widens and corrects the shape of the skull, as well as increasing the length of the lumbar vertebrae.

TYRA-300, an FGFR3-selective inhibitor, promotes bone growth in two FGFR3-driven models of chondrodysplasia - PubMed

Achondroplasia (ACH) and hypochondroplasia (HCH), the two most common types of dwarfism, are each caused by FGFR3 gain-of-function mutations that result in increased FGFR3 signaling, which disrupts chondrogenesis and osteogenesis, resulting in disproportionately shortened long bones. In this...

pubmed.ncbi.nlm.nih.gov

RESULTS
FGFR3 is one of your genetic enemies. If your goal is to maximise height and achieve the right facial proportions, you cannot afford to ignore this receptor. The use of selective inhibitors (such as TYRA-300 or ASP5878)

can u make a guide on skin maxxing and under eye wrinkles cause i got the wrinkles and dont know how to get rid of them

 

[JOTAROSON]

@diditeverbegin What made you laugh so much?

 

[Zagro]

@Zagro @Genio is this valid?

Genio is banned don’t ping him

 

[Jesus_ist_König]

Genio is banned don’t ping him

Oh oh
can you answer question though? if this is valid

 

[Zagro]

Oh oh
can you answer question though? if this is valid

FGFR3 works good for proliferation but depletes resting zone chondrocytes faster (saw this claim from a tiktok video while rotting but it was backed up), so no it’s not good, maybe could be beneficial only with absolute low doses

 

[JOTAROSON]

FGFR3 хорошо способствует пролиферации, но быстрее истощает запасы хондроцитов в зоне покоя (я видел это утверждение в видео в TikTok, пока гнил, но оно было подтверждено), поэтому нет, это не полезно, возможно, может быть полезно только в абсолютно низких дозах.

I literally attached studies in low doses, these are just auxiliary drugs. They are only needed to inhibit

 

[diditeverbegin]

@diditeverbegin What made you laugh so much?

Emojis and cat picture

 

[diditeverbegin]

Honestly I was initially skeptical but the success with wild type mice has intrigued me

 

[JOTAROSON]

Честно говоря, поначалу я был настроен скептически, но успехи с мышами дикого типа меня заинтриговали.

This is just the tip of the iceberg, these should not be the main drugs, but only secondary ones

 

[JOTAROSON]

Можете ли вы сделать руководство по улучшению состояния кожи и борьбе с морщинами под глазами, потому что у меня есть морщины, и я не знаю, как от них избавиться?

Send me your eyes, I'll see

 

[Zagro]

I literally attached studies in low doses, these are just auxiliary drugs. They are only needed to inhibit

Zero evidence for it being good for us with normal working FGFR3 gene, all the studies are on achondroplasia models so we don't know what would happen in healthy indivduals

 

[JOTAROSON]

Нет никаких доказательств того, что это полезно для нас при нормально функционирующем гене FGFR3, все исследования проводились на моделях ахондроплазии, поэтому мы не знаем, что произойдет у здоровых людей.

That's the interesting part, a little secret.

 

[JOTAROSON]

Нет никаких доказательств того, что это полезно для нас при нормально функционирующем гене FGFR3, все исследования проводились на моделях ахондроплазии, поэтому мы не знаем, что произойдет у здоровых людей.

If it's not too much trouble, please give me some topic for the post, then rate it, as I see you are an authority here

 

[vi24v_]

FGFR3 and its inhibitors

FGFR3 is a transmembrane protein that acts as a highly specific receptor on the cell surface. As a critical component of the cellular signalling system, it plays a central role in regulating fundamental biological processes such as cell proliferation, differentiation, migration and survival.

View attachment 4800612

Spoiler: Sphere of influence

The primary function of FGFR3 is to regulate growth and development. This receptor is best known for its crucial role in controlling bone growth. In particular, FGFR3 acts as a key negative regulator of longitudinal bone growth by influencing the activity of chondrocytes in the skeletal growth plates

IN OTHER WORDS, IT CAUSES ACHONDROPLASIA, A RECEDING JAWLINE, POOR BODY PROPORTIONS, AND SO ON




INHIBITORS



1)HGH - Forceful suppression
The first and most tried-and-tested method is to ‘flood’ the system with doses of GH in order to override the receptor’s resistance.
hGH stimulates proliferation via IGF-1, counteracting the signals from FGFR3.

View attachment 4800633

Spoiler: RESEARCH

In a study of children with growth disorders (achondroplasia), a daily dose of 1 IU/kg per week resulted in a phenomenal increase. Growth rates jumped from a meagre 3.2 cm to an impressive 8.3 cm per year.

Growth and growth hormone therapy in children with achondroplasia: a two-year experience - PubMed

The efficacy and safety of recombinant human growth hormone (hGH) administration was studied in children with achondroplasia. Fifteen children with achondroplasia, seven boys (4.8-12.2 years of age) and 12 girls (5.7-2.2 years of age), were treated daily with hGH at a dosage of 1 IU/kg/week...

pubmed.ncbi.nlm.nih.gov

THE MAIN NUANCE
HGH does not switch off FGFR3; it simply overpowers the receptor’s inhibitory system



2)ASP5878 - An oral receptor inhibitor
ASP5878 is a selective inhibitor of FGFR tyrosine kinase. It was originally developed to treat tumours, but has proved to be a goldmine for growth.

Unlike its injectable counterparts, this drug is taken orally (in tablet form).

View attachment 4800650

Spoiler: RESEARCH

A dose of 300 μg/kg resulted in significant bone elongation in the models.
A positive trade-off between the therapeutic dose and side effects (minimal effect on the corneal epithelium)

Evaluation of FGFR inhibitor ASP5878 as a drug candidate for achondroplasia - PubMed

Achondroplasia is caused by gain-of-function mutations in FGFR3 gene and leads to short-limb dwarfism. A stabilized analogue of C-type natriuretic peptide (CNP) is known to elongate bone by interacting with FGFR3 signals and thus is a promising drug candidate. However, it needs daily...

pubmed.ncbi.nlm.nih.gov

makes it an extremely promising option for those who don’t want to have their skin pierced every day.


3)TYRA300 - It is an innovative selective FGFR3 inhibitor that acts like a molecular sniper.


View attachment 4800637

Spoiler: RESEARCH

Experiments have shown not only an increase in the length of long bones (thighs, lower legs), but also an increase in naso-anal length (overall height).
Skull and spine: The preparation addresses a critical issue — stenosis of the foramen magnum. It widens and corrects the shape of the skull, as well as increasing the length of the lumbar vertebrae.

TYRA-300, an FGFR3-selective inhibitor, promotes bone growth in two FGFR3-driven models of chondrodysplasia - PubMed

Achondroplasia (ACH) and hypochondroplasia (HCH), the two most common types of dwarfism, are each caused by FGFR3 gain-of-function mutations that result in increased FGFR3 signaling, which disrupts chondrogenesis and osteogenesis, resulting in disproportionately shortened long bones. In this...

pubmed.ncbi.nlm.nih.gov

RESULTS
FGFR3 is one of your genetic enemies. If your goal is to maximise height and achieve the right facial proportions, you cannot afford to ignore this receptor. The use of selective inhibitors (such as TYRA-300 or ASP5878)

Mirin good thread

 

[Zagro]

If it's not too much trouble, please give me some topic for the post, then rate it, as I see you are an authority here

The post is pretty nice people tend to overlook the effect of rhGH on FGFR3 as they think it only affects GH/IGF-1, and also tyra-300 is like 3k USD per gram so not really realistic

And that ASP oral comp seems to inhibit FGFR 1-4, it's used on 3 week old rats for 2 weeks for 2 weeks: this means we don't really know the long-term effects nor the adverse effects in humans, FGFR2 and FGFR4 might be the only FGFRs worth inhibiting but FGFR2 wont have any importance after like age 15-16 and i can't see how significant ASP inhibits FGFR3 and at what minimal concentration. Infigratinib is the best choice for this as it's the most potent inhibitor for FGFR3 (that's affordable) and inhibits it at 2-fold lower concentrations then something like erdafitinib.

rhGH should always be the base compound for heightmaxxing
Tyra-300 only available for richcells
ASP gets mogged by infigratinib

We don't have information on non-achondroplasia patients or models or non-FGFR3 deleted/knockout models so it's hard to know but it seems good in deletion/knockout rats

 

[JOTAROSON]

The post is pretty nice people tend to overlook the effect of rhGH on FGFR3 as they think it only affects GH/IGF-1, and also tyra-300 is like 3k USD per gram so not really realistic

And that ASP oral comp seems to inhibit FGFR 1-4, it's used on 3 week old rats for 2 weeks for 2 weeks: this means we don't really know the long-term effects nor the adverse effects in humans, FGFR2 and FGFR4 might be the only FGFRs worth inhibiting but FGFR2 wont have any importance after like age 15-16 and i can't see how significant ASP inhibits FGFR3 and at what minimal concentration. Infigratinib is the best choice for this as it's the most potent inhibitor for FGFR3 (that's affordable) and inhibits it at 2-fold lower concentrations then something like erdafitinib.

rhGH should always be the base compound for heightmaxxing
Tyra-300 only available for richcells
ASP gets mogged by infigratinib

We don't have information on non-achondroplasia patients or models or non-FGFR3 deleted/knockout models so it's hard to know but it seems good in deletion/knockout rats

View attachment 4800881

I agree with you. I wanted to write about infigratinib, but I was too lazy. These are purely theoretical drugs. I just talked about the gene and the drugs. What post would you recommend next?

 

[diditeverbegin]

Zero evidence for it being good for us with normal working FGFR3 gene, all the studies are on achondroplasia models so we don't know what would happen in healthy indivduals

Tyra-300 as well? I have not looked at the other drugs, only Tyra; I doubt it’s practically accessible

 

[Zagro]

Tyra-300 as well? I have not looked at the other drugs, only Tyra; I doubt it’s practically accessible

It's accessible but expensive, the problem is not the compound the problem is inhibiting FGFR3 itself there's no great evidence on its effects for our use-case

 

[JOTAROSON]

Он доступен, но дорог. Проблема не в самом соединении, а в подавлении самого FGFR3. Достоверных доказательств его эффективности в нашем случае нет.

Please suggest a topic for a new post.

 

[Zagro]

Please suggest a topic for a new post.

HDAC inhibitors

 

[diditeverbegin]

It's accessible but expensive, the problem is not the compound the problem is inhibiting FGFR3 itself there's no great evidence on its effects for our use-case

I meant practically accessible because of the price

 

[birthdefect]

FGFR3 and its inhibitors

FGFR3 is a transmembrane protein that acts as a highly specific receptor on the cell surface. As a critical component of the cellular signalling system, it plays a central role in regulating fundamental biological processes such as cell proliferation, differentiation, migration and survival.

View attachment 4800612

Spoiler: Sphere of influence

The primary function of FGFR3 is to regulate growth and development. This receptor is best known for its crucial role in controlling bone growth. In particular, FGFR3 acts as a key negative regulator of longitudinal bone growth by influencing the activity of chondrocytes in the skeletal growth plates

IN OTHER WORDS, IT CAUSES ACHONDROPLASIA, A RECEDING JAWLINE, POOR BODY PROPORTIONS, AND SO ON




INHIBITORS



1)HGH - Forceful suppression
The first and most tried-and-tested method is to ‘flood’ the system with doses of GH in order to override the receptor’s resistance.
hGH stimulates proliferation via IGF-1, counteracting the signals from FGFR3.

View attachment 4800633

Spoiler: RESEARCH

In a study of children with growth disorders (achondroplasia), a daily dose of 1 IU/kg per week resulted in a phenomenal increase. Growth rates jumped from a meagre 3.2 cm to an impressive 8.3 cm per year.

Growth and growth hormone therapy in children with achondroplasia: a two-year experience - PubMed

The efficacy and safety of recombinant human growth hormone (hGH) administration was studied in children with achondroplasia. Fifteen children with achondroplasia, seven boys (4.8-12.2 years of age) and 12 girls (5.7-2.2 years of age), were treated daily with hGH at a dosage of 1 IU/kg/week...

pubmed.ncbi.nlm.nih.gov

THE MAIN NUANCE
HGH does not switch off FGFR3; it simply overpowers the receptor’s inhibitory system



2)ASP5878 - An oral receptor inhibitor
ASP5878 is a selective inhibitor of FGFR tyrosine kinase. It was originally developed to treat tumours, but has proved to be a goldmine for growth.

Unlike its injectable counterparts, this drug is taken orally (in tablet form).

View attachment 4800650

Spoiler: RESEARCH

A dose of 300 μg/kg resulted in significant bone elongation in the models.
A positive trade-off between the therapeutic dose and side effects (minimal effect on the corneal epithelium)

Evaluation of FGFR inhibitor ASP5878 as a drug candidate for achondroplasia - PubMed

Achondroplasia is caused by gain-of-function mutations in FGFR3 gene and leads to short-limb dwarfism. A stabilized analogue of C-type natriuretic peptide (CNP) is known to elongate bone by interacting with FGFR3 signals and thus is a promising drug candidate. However, it needs daily...

pubmed.ncbi.nlm.nih.gov

makes it an extremely promising option for those who don’t want to have their skin pierced every day.


3)TYRA300 - It is an innovative selective FGFR3 inhibitor that acts like a molecular sniper.


View attachment 4800637

Spoiler: RESEARCH

Experiments have shown not only an increase in the length of long bones (thighs, lower legs), but also an increase in naso-anal length (overall height).
Skull and spine: The preparation addresses a critical issue — stenosis of the foramen magnum. It widens and corrects the shape of the skull, as well as increasing the length of the lumbar vertebrae.

TYRA-300, an FGFR3-selective inhibitor, promotes bone growth in two FGFR3-driven models of chondrodysplasia - PubMed

Achondroplasia (ACH) and hypochondroplasia (HCH), the two most common types of dwarfism, are each caused by FGFR3 gain-of-function mutations that result in increased FGFR3 signaling, which disrupts chondrogenesis and osteogenesis, resulting in disproportionately shortened long bones. In this...

pubmed.ncbi.nlm.nih.gov

RESULTS
FGFR3 is one of your genetic enemies. If your goal is to maximise height and achieve the right facial proportions, you cannot afford to ignore this receptor. The use of selective inhibitors (such as TYRA-300 or ASP5878)

decent tbh, but asp is straight useless for this since its not specific to fgfr3
may as well use infig or erda at that point, which are unideal as well
tyra is likely fire tho

 

[birthdefect]

HDAC inhibitors

i just dont believe they have height benefits, its impossible to me
id love to be proven wrong tho, the reasoning behind it just seems like utter broscience

It's accessible but expensive, the problem is not the compound the problem is inhibiting FGFR3 itself there's no great evidence on its effects for our use-case

fgfr3 is like the negative regulator, it would be more surprising if it had no effect than it having a beneficial effect

 

[JOTAROSON]

Я просто не верю, что они дают преимущества, связанные с ростом, это для меня невозможно.
Мне бы очень хотелось ошибиться, хотя логика здесь кажется полнейшей невежественной чепухой.

FGF-FR3 действует как отрицательный регулятор, и было бы удивительнее, если бы он не оказывал никакого эффекта, чем если бы он оказывал благотворное воздействие.

I also thought about the HDAC inhibitor and realized that there was no point in making a post about it, because almost everyone knows about it.

 

[birthdefect]

I also thought about the HDAC inhibitor and realized that there was no point in making a post about it, because almost everyone knows about it.

almost everyone knows about fgfr3i as well tbh
hdaci, dnmti, ezhi, etc. are all way less common, if you make a high iq thread about it with decent formatting thats basically one of a kind

 

[JOTAROSON]

Честно говоря, о fgfr3i знают почти все.
hdaci, dnmti, ezhi и т.д. встречаются гораздо реже, и если вы создадите на эту тему тему с хорошим форматированием, это будет практически уникальный случай.

I'm currently working on a slightly different post, it's related to theoretical growth after growth zones close, I might do that later

 

[Zagro]

i just dont believe they have height benefits, its impossible to me
id love to be proven wrong tho, the reasoning behind it just seems like utter broscience

Because you look at hdac knockout rats and compare it to low dose HDACi just like how we have zero non-achondroplasia models for fgfr

fgfr3 is like the negative regulator, it would be more surprising if it had no effect than it having a beneficial effect

Yeah but good luck getting tyra-300 cause infigratinib or erdafitinib; pan hdacs will stunt your growth cause it will accelerate msc/rzc and chondrocyte differentiation significantly

 

[birthdefect]

Because you look at hdac knockout rats and compare it to low dose HDACi just like how we have zero non-achondroplasia models for fgfr


Yeah but good luck getting tyra-300 cause infigratinib or erdafitinib; pan hdacs will stunt your growth cause it will accelerate msc/rzc and chondrocyte differentiation significantly

if you mean like resting zone cell differentiation, erda nor infig will do that
fucking hell ive had this response open for an hour and i forgot why it wont do that
just use low dose tyra and profit

i really wanna hear more about hdacs, but idk much about them

 

[Arbuscular]

1 IU/kg

nigger I can't afford this

 

[Zagro]

if you mean like resting zone cell differentiation, erda nor infig will do that
fucking hell ive had this response open for an hour and i forgot why it wont do that
just use low dose tyra and profit

i really wanna hear more about hdacs, but idk much about them

erda and infig will both do that and using low doses of fgfri doesn't really work pretty sure as you need to reach a certain concentration to actually inhibit it afaik and you also cant dose it just so you can only inhibit fgfr3 so it cant be half assed. Inhibiting fgfr2 will be the biggest mistake you'll make because as you age your endogenous fgfr2 already lowers so inhibiting that is just like using some shit like somatostatin; age mediated decline in gh and fgfr2, but fgfr2 just stops when plates fully ossify

Just like how pan hdacs are bad for height, pan fgfr inhibitors are also bad as the only good thing with hdacs is inhibiting hdac6 and with fgfr its fgfr3

 

[Zagro]

nigger I can't afford this

per week negro you just need a job

 

[Arbuscular]

per week negro you just need a job

I read per day mb

 

[birthdefect]

erda and infig will both do that and using low doses of fgfri doesn't really work pretty sure as you need to reach a certain concentration to actually inhibit it afaik and you also cant dose it just so you can only inhibit fgfr3 so it cant be half assed. Inhibiting fgfr2 will be the biggest mistake you'll make because as you age your endogenous fgfr2 already lowers so inhibiting that is just like using some shit like somatostatin; age mediated decline in gh and fgfr2, but fgfr2 just stops when plates fully ossify

Just like how pan hdacs are bad for height, pan fgfr inhibitors are also bad as the only good thing with hdacs is inhibiting hdac6 and with fgfr its fgfr3

i agree pan fgf inhibitors are a mistake
fgfr3i alone is necessary
isnt hdaci for hdac6 alone just redundant with tyra?

 

[JOTAROSON]

I read per day mb

I don't care, if you don't have money, it's not my problem. You could have just asked me to make a post about more affordable drugs.

 

[JOTAROSON]

Я согласен, что пан-ингибиторы FGF — это ошибка.
Для этого достаточно одного лишь fgfr3i.
Разве использование только HDAC6 для HDAC6 не является излишним при помощи Tyra?

I'll make a post about it soon HDAC I can mark it for you if you want

 

[birthdefect]

I'll make a post about it soon HDAC I can mark it for you if you want

do tag