GSK-2881078 vs LGD-3303

Performance

Performance

Research Only

Research Only

GSK-2881078 is a nonsteroidal small molecule built on an indole-5-carbonitrile scaffold that binds the androgen receptor to produce tissue-selective anabolic effects in skeletal muscle, with intended reduced activity in prostate and other androgen-sensitive tissues relative to testosterone. No published crystal structure or binding-affinity (Ki/EC50) data for the androgen receptor were located, so the precise selectivity mechanism versus other tissues is not independently confirmed beyond the class description used in clinical trial publications.

LGD-3303 is a nonsteroidal androgen receptor (AR) agonist. In castrated rat studies (Vajda et al. 2009, PMID 19017848), it bound and activated the AR to drive potent anabolic activity in levator ani muscle while acting only as a partial agonist in androgenic tissues (preputial gland, ventral prostate), never stimulating ventral prostate above intact-animal levels despite rising plasma concentrations. Tissue-selective activity persisted regardless of oral versus continuous-infusion dosing and despite higher local drug concentrations in prostate than in muscle, indicating the selectivity arises from altered molecular interaction at the AR itself rather than from differences in pharmacokinetic exposure or tissue distribution.