entinostat-bottlebrush prodrug

Entinostat-BPD is an experimental nanoparticle-based epigenetic therapy that utilizes a bottlebrush prodrug (BPD) platform for the tumor-selective delivery of entinostat, a Class I histone deacetylase (HDAC) inhibitor. Developed through a collaboration involving the Salk Institute and MIT, this platform is designed to mitigate the systemic toxicities that have historically limited the clinical utility of HDAC inhibitors. Mechanistically, the drug inhibits HDAC1 and HDAC2, which triggers a genome-wide redistribution of H3K27 acetylation. This redistribution diverts essential transcriptional machinery, such as BRD4 and RNA polymerase II, away from the promoters of DNA damage response (DDR) genes, thereby suppressing their expression. By impairing the cell's ability to repair DNA, Entinostat-BPD sensitizes tumors—specifically pancreatic ductal adenocarcinoma (PDAC)—to DNA-damaging agents including platinum-based chemotherapies, topoisomerase inhibitors, and PARP inhibitors. Preclinical studies indicate that this nanoparticle formulation achieves comparable tumor suppression to free entinostat with significantly reduced drug exposure and toxicity.

Other names

entinostat + benzoporphyrin derivative