RLA-5286

RLA-5286 is a ferrous iron-activatable drug conjugate (FeADC) designed for the treatment of metastatic castration-resistant prostate cancer (mCRPC). It consists of the second-generation androgen receptor antagonist enzalutamide conjugated to a trioxolane (TRX) trigger. The drug leverages the elevated levels of labile ferrous iron (Fe2+) found in advanced prostate cancer cells; the TRX moiety reacts with intracellular Fe2+ via a Fenton-like reaction to selectively release the active enzalutamide payload within the tumor microenvironment. This targeted delivery mechanism is intended to improve the therapeutic index of enzalutamide by concentrating the drug in tumor tissue while minimizing systemic exposure and brain penetration, thereby potentially reducing dose-limiting central nervous system toxicities such as seizures.