AR-p300 DALTAC-1

AR-p300 DALTAC-1 is a first-in-class Domain-ALTeration Chimera (DALTAC) designed for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Unlike traditional inhibitors or degraders, this chemical-induced proximity compound rewires endogenous protein complexes by enforcing proximity between the Androgen Receptor (AR) ligand-binding domain and the p300 bromodomain. This domain reconfiguration locks the AR-p300 complex in a non-productive configuration, effectively collapsing the oncogenic neo-enhanceosome network. Mechanistically, it reprograms the substrate spectrum of p300, specifically diminishing histone H2B N-terminal acetylation (H2BNTac), which leads to potent suppression of AR target gene transcription and cell proliferation. Developed by researchers at the University of Michigan, DALTAC-1 has demonstrated robust antitumor efficacy and lineage selectivity in prostate cancer models with a favorable safety profile.

Other names

AR-p300 DALTAC-1AR-p-300 DALTAC-1AR-p 300 DALTAC-1