MPC309

MPC309 is a multivalent peptoid conjugate (MPC) designed for the treatment of castration-resistant prostate cancer (CRPC). It consists of a peptoid scaffold that displays three copies of ethisterone, a known androgen receptor (AR) antagonist. This multivalent presentation increases the effective local concentration of the ligand, enabling high-affinity binding to the AR and disrupting its interaction with coregulators. MPC309 has shown efficacy in reducing the proliferation of prostate cancer cells resistant to enzalutamide, including those expressing AR splice variants or harboring ligand-binding domain mutations. The compound enters cells through macropinocytosis, a mechanism that may provide cancer cell-specific delivery. In preclinical studies, MPC309 demonstrated superior tumor suppression in xenograft models compared to enzalutamide by inducing a distinct gene expression profile through the modulation of AR chromatin occupancy.