TH588

Description: TH588 is a novel and highly potent inhibitor of human 7, 8-Dihydro-8-oxoguaninetriphosphatase MTH1 (NUDT1) with an IC50 of 5 nM. It has good metabolic stability. Cancers have dysfunctional redox regulation resulting in reactive oxygen species production, damaging both DNA and free dNTPs. The MTH1 protein sanitizes oxidized dNTP pools to prevent incorporation of damaged bases during DNA replication. TH588 a first-in-class nudix hydrolase family inhibitor that potently and selectively engages and inhibits the MTH1 protein in cells. Protein co-crystal structures demonstrate that the inhibitor binds in the active site of MTH1.

References: Saleh A, Gökturk C, Warpman-Berglund U, Helleday T, Granelli I. Development and validation of method for TH588 and TH287, potent MTH1 inhibitors and new anti-cancer agents, for pharmacokinetic studies in mice plasma. J Pharm Biomed Anal. 2015 Feb; 104:1-11. doi: 10.1016/j.jpba.2014.11.009. Epub 2014 Nov 15. PubMed PMID: 25459754.