COMMENT TH5427 is potent and selective chemical probe for NUDT5, a NUDIX hydrolase enzyme that plays important roles in the metabolism of adenosine-5’-diphisphoribose (ADPR) metabolism and regulation of hormone signaling. NUDT5 has been implicated in breast cancer, and TH5427 should provide a valuable tool for the continued exploration of the role of this target in breast cancer and other diseases models. TH5427 is at least 690-fold selective for NUDT5 over other NUDIX hydrolases in vitro, with only limited demonstrated interactions outside of the NUDIX hydrolyase family. I recommend the use of this probe in cells at concentrations up to 1.5 µM, with demonstrated effectiveness in HL-60 and T47D cells. TH5427 does show a large cellular potency offset comparing potency in vitro (malachite green assay, 29 nm) vs in cellular target engagement assays (CETSA and DARTS, 0.75-2.1 µM), though this potency offset has not been specifically explained (i.e. cellular availability vs metabolite competition or other factors). Jul 11 2020 - 3:00pm; TH5427 showed 690-fold selectivity for NUDT5 over MTH1 in direct assay of ADP-ribose hydrolysis in vitro. Jul 26 2020 - 10:06am

DESCRIPTION TH5427 is a promising, targeted inhibitor that can be used to further study NUDT5 activity and ADP-ribose metabolism. TH5427, blocks progestin-dependent, PAR-derived nuclear ATP synthesis and subsequent chromatin remodeling, gene regulation and proliferation in breast cancer cells. NUDT5 is recently identified as a rheostat of hormone-dependent gene regulation and proliferation in breast cancer cells[1].

PRICE 319

DESCRIPTION TH5427 is a lead NUDT5 inhibitor(MG assay IC50?=?29?nM).

MOA Inhibitor (Chemical Probes.org)

DESCRIPTION Potent and selective ATP-competitive CDK9 inhibitor (Tocris Bioactive Compound Library)

DESCRIPTION TH5427 is a lead NUDT5 inhibitor(MG assay IC50 = 29 nM). (TargetMol Bioactive Compound Library)