Design, Synthesis and Anti-Tumor Evaluation of Novel Thiohydantoin Congeners as Androgen Receptor Antagonists With In Vivo Study

The efficacy of degrading the androgen receptor through dermal application in DP cells, a delivery system for topical drugs that involves dissolving microneedles, and rosemary oil as an alternative anti-androgen.

FCE 28260 (PNU 156765), an under-explored 5α-reductase inhibitor, showcases promising results in research by Giudici et al., outperforming well-known treatments like Finasteride in reducing the conversion of testosterone to DHT. Its superior efficacy, demonstrated through lower IC50 values in both natural and human recombinant enzyme studies, suggests it could offer more effective management of DHT-related conditions. Additionally, its lower molecular weight hints at better potential for topical application, potentially offering advantages in treating conditions such as androgenic alopecia. Despite its potential, it has not advanced in development, possibly due to financial limitations, leaving its therapeutic prospects and side effect profile largely unexplored.

The conversation discusses GT20029, a compound by Kintor Pharma that degrades androgen receptors and is in trials, with potential as a hair loss cure. Another promising treatment mentioned is an antibody that blocks prolactin and has shown positive results in macaques.

The conversation discusses topical androgen receptor blockers for hair loss, mentioning Clascoterone, Pyrilutamide, GT20029, and RU58841. Ketoconazole's effectiveness and application methods are also debated.

Pyrilutamide is a selective AR antagonist with a high binding affinity, making it effective in competing with DHT for androgen receptors. The 1% concentration is more effective than the 0.5%, but the latter may suffice for mild hair loss; the drug is considered a good option for those avoiding 5AR blockers due to side effects.

GT20029 and pyrilutamide are both androgen antagonists but work differently; GT20029 degrades the androgen receptor, while pyrilutamide blocks DHT from binding. GT20029 is expected to have similar efficacy to CosmeRNA.