molecules of the month

Context. GNE-064 (Genentech) is an oral inhibitor of the bromodomains of SMARCA2/4 and PBRM1 being developed as a tool compound. Many proteins contain bromodomains (there are 61 in the human genome), which recognize acetyl lysines and are involved in regulating gene transcription. Proteins that contain bromodomains are often mutated in cancers, and bromodomains are considered to be important drug targets in a variety of cancers, with several such compounds targeting BET-family and CREBBP/EP300 bromodomains having made it into the clinic. Despite being the least druggable bromodomain proteins as predicted by binding pocket structural analysis and challenges with identifying strong enough probes, SMARCA2/4 tool compounds have been developed, such as PFI-3 and GNE-064. Target. Acetylation of lysine residues on histones and…