I'm conducting a group buy for a couple dozen compounds with a reputable lab in China. The supplier is ordering materials this week, and synthesis will begin shortly. Some items are already in stock. I have attached a pricing list for all available items. Disregard KDS2010 and Compound 60, as those two are not currently available. Most of the compounds we are ordering are for the purpose of treating hair loss. There are many Wnt disinhibitors and androgen/TGFbeta pathway inhibitors. Some of the compounds can be of use as anti-aging or cancer therapies. There is also a highly potent ROCK inhibitor, 30x more potent than Y-27632. ROCK is a mediator of fibrosis, and may be an effective treatment for erectile dysfunction.
TM5614 is perhaps the best anti-aging compound to date. There is an Amish community in which some members have a null mutation in the SERPINE1 gene that codes for PAI-1. Homozygous carriers do not produce the protein, while heterozygous carriers have roughly half the PAI-1 levels of other members of their community. Heterozygous carriers of the mutation show no negative effects. Compared to non-carriers in the community, they appear younger, have better cardiovascular health, no diabetes, longer telomeres, and they live 14 years longer on average. TM5614 is designed to mimic this mutation, reducing PAI-1 levels by about 50%. It is currently in clinical trials for chronic myeloid leukemia, where the dose is 150-180mg once daily. It is slated to enter clinical trials for hair loss and gray hair. TM5614 reduces PCSK9 and fibrosis, while increasing nitric oxide. Some people are already using this compound. Younger people don't report much, but older people report feeling better than they have in years.
PAI-1 is one of the most predictive biomarkers for infirmity
https://link.springe...357-022-00685-2
It is a marker and mediator of senescence
https://www.ncbi.nlm...les/PMC5846199/
https://www.tohoku.a..._healthier.html
https://pubmed.ncbi....h.gov/28378522/
Other items the community may be interested in:
BMS-202 It may reverse gray hair. It is a small molecule targeting the same pathway as monocolonal antibodies that have been shown to reverse gray hair with remarkable consistency.
https://jamanetwork....bstract/2663945
Rapamycin is also available, this needs no introduction.
There is also a pan-mTOR inhibitor, sapanisertib, which is more effective against cancer. Pulse therapy may have some use in anti-aging.
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The superiority of INK128 as an mTOR inhibitor is also evident in its ability to reprogram the mTOR oncogenic translational program in prostate cancer, which is not achieved by rapalog treatment.”
https://www.ncbi.nlm...les/PMC3663483/
Many of these compounds may have value as cancer therapies, particularly harmine 19a, a TWIST1 inhibitor. TWIST1 is also upregulated during aging, and may be a good target for anti-aging therapy. it is involved in several diseases of aging, such as cachexia, alzheimer's, male pattern baldness, reduced lung function, and cardiovascular disease. Twist1 is important during development, but is downregulated postnatally, and rarely expressed in adult tissue outside of a diseased state.
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we show that Twist1 is required for skin tumor initiation and progression in a gene-dosage-dependent manner. Moreover, conditional ablation of Twist1 in benign tumors leads to increased apoptosis, reduced cell proliferation, and defective tumor maintenance and propagation independently of its EMT-inducing abilities.
These results reveal that Twist1 is required for tumor initiation and maintenance in a p53-dependent and -independent manner.
https://www.cell.com...5909(14)00560-8
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We found that upregulation of Twist1 mediates age-dependent decline in angiogenesis through PGC1α and VEGFR2 expression.
Twist1 is also involved in DNA methylation and cellular senescence, which are associated with aging processes
https://www.ncbi.nlm...les/PMC8034921/
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Addition of the ROCK inhibitor Y-27632, which inhibits both ROCK1 and ROCK2, resulted in significant tissue relaxation compared with vehicle (∼86%; P = 0.0016). When CCT was preincubated with the PDE5 inhibitor vardenafil (resulting in ∼24% relaxation) subsequent addition of Y-27632 caused an additional relaxation of ∼74% compared with vehicle.
In this study, we combine results on ROCK expression with functional data in the human setting for the first time, confirming that ROCK might be an interesting target for ED treatment,” Albersen told Nature Reviews Urology. “Several ROCK inhibitors are being developed for indications such as hypertension. A ROCK2-selective inhibitor might be more effective in ED and have fewer off-target effects, and combination of PDE5 and ROCK inhibition might enable reduced doses and enhanced effects in the penis.
https://bjui-journal....1111/bju.13691
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