Hypothesis The Double-edged Sword of @zaycism's guide on Dasatinib and Quercetin.

[Niggard]

Original thread:

Guide Dasatinib + Quercetin and Height Growth

Yesterday at 10:32 AM

introduction
This guide covers the dasatinib + quercetin (D+Q) height growth hypothesis. Including the biological rationale, how it might affect growth plates, and the evidence that’s currently available. Focusing on the role of cellular senescence in skeletal development.

what are dasatinib and quercetin?

Dasatinib is an anticancer drug, a second-generation tyrosine kinase inhibitor (TKI).
It potently inhibits BCR-ABL and SRC family kinases (non-receptor tyrosine kinases that interact to drive cell proliferation and...​

• zaycism
• Replies: 32
• Forum: Looksmaxxing

• 
• 

Spoiler: TLDR;

Dasatinib is harmful for longitudinal bone growth.

The analysis brought by @zaycism is impaired. The study was on PDE (Prenatal Dexamethasone Exposure) rats.

Study link: https://pmc.ncbi.nlm.nih.gov/articles/PMC12540037/
This makes it irrelevant to consider when testing on healthy people. Dasatinib is harmful because...

The tyrosine kinase inhibitor dasatinib (SPRYCEL) inhibits chondrocyte activity and proliferation - PMC

pmc.ncbi.nlm.nih.gov

https://www.researchgate.net/publication/333836774_GROWTH_RATE_AND_ENDOCRINE_EFFECTS_OF_DASATINIB_THERAPY_OBSERVED_IN_A_RETROSPECTIVE_ANALYSIS_OF_A_PHASE_2_CLINICAL_TRIAL_FOR_PEDIATRIC_PATIENTS_WITH_CHRONIC_MYELOID_LEUKEMIA_IN_CHRONIC_PHASE_CML-CP_PF4

Study one shows that dasatinib causes decreased chondrocyte activity and proliferation. Study two shows no height difference in using dasatinib alone.

Why did it work in the PDE study then??

Because cells damaged by dexamethasone fall into pathological senescence, and dasatinib caused apoptosis of such, and with quercetin, which indeed is potent, this caused a synergistic effect. However, in healthy individuals, dasatinib would only have a harming effect.

A compound like erdafitinib would be much better to pair with quercetin. They both interact with SOX9 symphonically.

Peace pookies

 

[Niggard]

Even ignoring PDE, it's going to harm shit because like, you can think of it as non-selective, it harms progenitor cells and other profileration related ones which causes it's decrease, this dasatinib is shit!

 

[zaycism]

ur treating D+Q isn’t proven and that D+Q is harmful as the same conclusion. The data supports neither. D has anti-proliferative effects on chondrocytes in vitro, but pediatric clinical data doesn’t show clear growth suppression, and the PDE study still demonstrates a growth benefit in a living organism. the evidence is mixed, not one sided
also erda has even less direct evidence for height growth than D+Q, and FGFR modulation can have unpredictable effects on growth plates

 

[James]

ur treating D+Q isn’t proven and that D+Q is harmful as the same conclusion. The data supports neither. D has anti-proliferative effects on chondrocytes in vitro, but pediatric clinical data doesn’t show clear growth suppression, and the PDE study still demonstrates a growth benefit in a living organism. the evidence is mixed, not one sided
also erda has even less direct evidence for height growth than D+Q, and FGFR modulation can have unpredictable effects on growth plates

Fgf signaling should be left in the RZ imo.

 

[zaycism]

Fgf signaling should be left in the RZ imo.

thats exactly y im skeptical of erdafitinib as a height compound. fgf signaling has different roles across the growth plate, so broadly inhibiting fgfrs doesnt mean increased growth. atl D+Q has some senolytic data behind it, even if the evidence is mixed

 

[James]

thats exactly y im skeptical of erdafitinib as a height compound. fgf signaling has different roles across the growth plate, so broadly inhibiting fgfrs doesnt mean increased growth. atl D+Q has some senolytic data behind it, even if the evidence is mixed

Erda is net positive, very strong for velocity, theres a better way to potentiate the same pathway though… . Also the main negatives of fgfr1-2 inhibition is osteogeneic. But I think there will be one possible negative with fgfr3I in rz.

 

[Niggard]

ur treating D+Q isn’t proven and that D+Q is harmful as the same conclusion. The data supports neither. D has anti-proliferative effects on chondrocytes in vitro, but pediatric clinical data doesn’t show clear growth suppression, and the PDE study still demonstrates a growth benefit in a living organism. the evidence is mixed, not one sided
also erda has even less direct evidence for height growth than D+Q, and FGFR modulation can have unpredictable effects on growth plates

Read below

Even ignoring PDE, it's going to harm shit because like, you can think of it as non-selective, it harms progenitor cells and other profileration related ones which causes it's decrease, this dasatinib is shit!

And also the claim that it doesn't show growth suppression is so shitty cuz the study in humans I linked shows it's useless and in vitro studies show us how exactly it negatively interacts with chondrocytes, as well as this:

https://www.thelancet.com/journals/lanwpc/article/PIIS2666-6065(23)00136-0/fulltext

Explains clear harm
Dasa only worked in PDE because it cleared the zombie cells which were stagnant due to be condition which so happened to be a net positive
Even FDA clearly states in it's warning label this about dasa: "Bone growth and development/Epiphyseal growth plate fusion anomalies"
It's shit

 

[Niggard]

B

 

[zaycism]

Read below

And also the claim that it doesn't show growth suppression is so shitty cuz the study in humans I linked shows it's useless and in vitro studies show us how exactly it negatively interacts with chondrocytes, as well as this:

https://www.thelancet.com/journals/lanwpc/article/PIIS2666-6065(23)00136-0/fulltext

Explains clear harm
Dasa only worked in PDE because it cleared the zombie cells which were stagnant due to be condition which so happened to be a net positive
Even FDA clearly states in it's warning label this about dasa: "Bone growth and development/Epiphyseal growth plate fusion anomalies"
It's shit

you are overstating the certainty
the chondrocyte and progenitor cell concerns are legitimate, and the fda warning plus reports of growth plate abnormalities definitely weigh against dasatinib n im not disputing that

i dispute jump from dasatinib has growth-related risks to D+Q can never have a net positive effect on growth plate biology

the pde study still demonstrated a growth benefit in vivo. u explain that by saying it only worked because pathological senescent cells were present, but thats still a mechanism, not a contradiction. the question becomes whether enough detrimental senescence exists in a normal growth plate for senolysis to offset dasas anti proliferative effects.
rn the evidence u showed is stating dasa can impair chondrocyte progenitor function, clear senescent cells and in atl one disease model the net effect was positive for growth

so its definitely not shit

 

[Niggard]

you are overstating the certainty
the chondrocyte and progenitor cell concerns are legitimate, and the fda warning plus reports of growth plate abnormalities definitely weigh against dasatinib n im not disputing that

i dispute jump from dasatinib has growth-related risks to D+Q can never have a net positive effect on growth plate biology

the pde study still demonstrated a growth benefit in vivo. u explain that by saying it only worked because pathological senescent cells were present, but thats still a mechanism, not a contradiction. the question becomes whether enough detrimental senescence exists in a normal growth plate for senolysis to offset dasas anti proliferative effects.
rn the evidence u showed is stating dasa can impair chondrocyte progenitor function, clear senescent cells and in atl one disease model the net effect was positive for growth

so its definitely not shit

Disease model. Not healthy individual model. Case closed.
And why not just use FOXO4?