CPI-455 (1628208-23-0) is a potent (IC50?= 10 nM) and selective inhibitor of the lysine demethylase KDM5 (equal inhibition of KDM5A, 5B, 5C).1?CPI-455 reduced the number of drug-tolerant persister cancer cells (DTPs) in a dose-dependent, KDM5-dependent manner in multiple cell lines treated with standard chemotherapy or targeted agents. CPI-455 synergized with 5-aza-2’-deoxycytidine (DAC) to reduce the viability of luminal breast cancer cells?in vitro.2?KDM5 demethylases have recently been shown to repress the immune response to tumors?via?suppression of STING.3
CPI-455 is a potent KDM5 demethylase inhibitor.
1) Vinogradova?et al.?(2016),?An inhibitor of KDM5 demethylases reduces survival of drug-tolerant cancer cells;?Nat. Chem. Biol.?12?531
2) Leadem?et al.?(2018),?A KDM5 Inhibitor Increases Global H3K4 Trimethylation Occupancy and Enhances the Biological Efficacy of 5-Aza-2’-Deoxycytidine;?Cancer Res.?78?1127
3) Wu?et al.?(2018),?KDM5 histone demethylases repress immune response via suppression of STING;?PLoS Biol.?16?e2006134dfd
