GSK343

GSK343 is a potent, selective, and cell-active small molecule inhibitor of the histone lysine methyltransferase EZH2 (Enhancer of zeste homolog 2). Developed by GSK and made available as a chemical probe in collaboration with the Structural Genomics Consortium (SGC), GSK343 inhibits EZH2 with an IC50 of 4 nM, demonstrating over 1,000-fold selectivity against other histone methyltransferases (except EZH1, for which it has 60-fold selectivity). It acts as a S-adenosyl-L-methionine (SAM)-competitive inhibitor, suppressing the trimethylation of histone H3 lysine 27 (H3K27me3). Due to poor pharmacokinetic properties, including high clearance in vivo, GSK343 is primarily utilized as a research-use-only laboratory tool to study EZH2 biology and epigenetic regulation in various cancer models, such as breast cancer, prostate cancer, ovarian cancer, and glioblastoma.

Other names

1-isopropyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-6-(2-(4-methylpiperazin-1-yl)pyridin-4-yl)-1H-indazole-4-carboxamideGSK 343GSK343GSK-343