IBG-P3

IBG-P3 is a prostate-specific membrane antigen (PSMA)-targeted intramolecular bivalent glue (IBG) conjugate designed for the selective degradation of bromodomain-containing protein 4 (BRD4) in prostate cancer cells. Developed by researchers at the University of Wisconsin-Madison, IBG-P3 consists of a picomolar-active, DCAF16-recruiting BRD4 degrader (IBG3) conjugated to a PSMA-targeting ligand via a cathepsin-sensitive cleavable linker and a dual-functional polycarboxylate linker. This design enhances PSMA binding and limits passive diffusion, thereby achieving tissue-selective BRD4 degradation and minimizing systemic toxicity. In preclinical models of advanced prostate cancer, including metastatic castration-resistant prostate cancer (mCRPC), IBG-P3 has demonstrated potent antitumor efficacy both as a monotherapy and in combination with targeted alpha therapy (such as [225Ac]Ac-PSMA).