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
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
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