A novel AR molecular glue degrader via bivalent engagement of the N-terminal domain and RNF213–UBE2J2 complex

The conversation discusses androgen receptor degraders for hair loss, highlighting their potential advantages over traditional AR blockers like RU58841 and pyrilutamide. Concerns about the safety and cost of these treatments are also mentioned.

RU58841 shows the strongest results despite weaker binding affinity, while KX-826 and CB-03-01 are more expensive and have minimal side effects. RU58841 is considered effective but has potential health risks if ingested; users report positive outcomes with RU58841 and finasteride.

RU58841 may pose cancer risks due to its antiandrogen properties and lack of long-term safety data. Using it is considered a high-risk experiment with unknown potential for harm.

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.

RU58841, an anti-androgenic compound, showed early promise for treating alopecia but faced challenges after its patent in 1997. Despite advancing to Phase II trials, safety concerns and financial struggles led Aventis to abandon its development. Proskelia, which later merged into ProStrakan, couldn't prioritize the drug, leading to its eventual stagnation and failure to reach the market.