TH588

TH588 is an MTH1 inhibitor (IC₅₀ = 5 nM) with improved metabolic stability over TH287 (Item No. 18132).¹ It selectively kills cancer cell lines (IC₅₀s = 2.48-6.37 µM) without significant cytotoxicity towards primary or immortalized cells (IC₅₀s = ≥20 µM) and demonstrates >1,000-fold selectivity for MTH1 over the related nudix hydrolase protein family members MTH2, NUDT5, NUDT12, NUDT14, and NUDT16, as well as other proteins with known nucleoside triphosphate pyrophosphatase activity (dCTPase, dUTPase, and ITPA).¹ At 30 mg/kg, TH588 induces incorporation of oxidized dNTPs in cancer cells, leading to DNA damage and cell death in B-Raf^V600E melanoma, SW480 colorectal, or MCF-7 breast tumor mouse xenografts.¹

WARNING This product is not for human or veterinary use.

1. Gad, H., Koolmeister, T., Jemth, A.S., et al. MTH1 inhibition eradicates cancer by preventing sanitation of the dNTP pool. Nature 508, 215-242 (2014).