TH588 hydrochloride, a first-in-class inhibitor of the nudix hydrolase family, selectively and effectively binds to and inhibits MTH1 with an IC50 value of 5 nM.

TH588 (2-10μM; 7-10 days) has demonstrated selective and effective cytotoxicity against various cancer cell lines, including U2OS, HeLa, MDA-MB-231, MCF-7, SW480, and SW620, with IC50 values of 1.38, 0.83, 1.03, 1.08, 1.72, and 0.80 μM, respectively. Conversely, it showed reduced toxicity towards primary or immortalized cell lines such as VH10 and HDFn. This efficacy underscores TH588's potential as a targeted cancer therapeutic agent.

TH588, administered subcutaneously at a dosage of 30 mg/kg once daily for 35 days, effectively reduces tumor growth in the SW480 xenograft cancer model, as demonstrated in a study involving 5-6 weeks old female SCID mice. This result underscores TH588's potential therapeutic efficacy in this specific cancer model. [1]