Description
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).1CPI-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 cellsin vitro.2KDM5 demethylases have recently been shown to repress the immune response to tumorsviasuppression of STING.3
References
[1] MAIA VINOGRADOVA. An inhibitor of KDM5 demethylases reduces survival of drug-tolerant cancer cells[J]. Nature chemical biology, 2016, 12 7: 531-538. DOI:
10.1038/nchembio.2085[2] BENJAMIN R LEADEM. A KDM5 Inhibitor Increases Global H3K4 Trimethylation Occupancy and Enhances the Biological Efficacy of 5-Aza-2’-Deoxycytidine.[J]. Cancer research, 2018: 1127-1139. DOI:
10.1158/0008-5472.can-17-1453[3] LIZHEN WU. KDM5 histone demethylases repress immune response via suppression of STING.[J]. PLoS Biology, 2018, 16 8: e2006134. DOI:
10.1371/journal.pbio.2006134
