Screen-identified selective inhibitor of lysine demethylase 5A blocks cancer cell growth and drug resistance.

ABSTRACT: Lysine demethylase 5A (KDM5A/RBP2/JARID1A) is a histone lysine demethylase that is overexpressed in several human cancers including lung, gastric, breast and liver cancers. It plays key roles in important cancer processes including tumorigenesis, metastasis, and drug tolerance, making it a potential cancer therapeutic target. Chemical tools to analyze KDM5A demethylase activity are extremely limited as available inhibitors are not specific for KDM5A. Here, we characterized KDM5A using a homogeneous luminescence-based assay and conducted a screen of about 9,000 small molecules for inhibitors. From this screen, we identified several 3-thio-1,2,4-triazole compounds that inhibited KDM5A with low μM in vitro IC50 values. Importantly, these compounds showed great specificity and did not inhibit

SUBMITTER: Gale M 

PROVIDER: S-EPMC5129982 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature