JMKX007129

JMKX007129 is a next-generation small-molecule androgen receptor (AR) inhibitor that specifically targets the N-terminal domain (NTD). Developed by Shanghai Jeyou Pharmaceutical, it is designed to address resistance in metastatic castration-resistant prostate cancer (mCRPC) caused by mutations in the AR ligand-binding domain (LBD) or the expression of AR splice variants such as AR-V7, which lack the LBD. By binding to the NTD, JMKX007129 inhibits the transcriptional activity of both full-length AR and AR-V7. Preclinical data indicate that the compound possesses high potency (EC50 ≈ 20 nM) and selectivity, favorable pharmacokinetic properties across multiple species (mice, rats, and dogs), and robust anti-tumor efficacy in models of both sensitive and resistant prostate cancer. As of early 2026, IND-enabling studies for JMKX007129 are in progress.