MTH1 Inhibitor, TH588

A cell-permeable, bioavailable diaminopyrimidine compound that acts as a potent, reversible, and active site targeting inhibitor of MTH1 (human MutT homolog 1; IC₅₀ = 5 nM). The inhibition appears to be substrate independent in nature. Shown to selectively kill human osteosarcoma (U2OS) and other cancer cells, but display much reduced cytotoxicity towards several primary cells. Causes incorporation of oxidized dNTPs into cancer cells, leading to cytotoxic DNA damage, independent of their p53 status. However, it can also trigger ATM-p53-mediated death response and DNA repair in U2OS cells. Does not display any inhibitory activity against 87 enzymes, GPCRs, protein kinases, ion channels, and transporters even at 10 µM levels. Effectively suppresses MCF7 and SW480 tumor xenografts in mice (30 mg/kg, s.c., q.d.).

A cell-permeable, bioavailable diaminopyrimidine compound that acts as a potent, reversible, and active site targeting inhibitor of MTH1 (human MutT homolog 1; IC₅₀ = 5 nM). The inhibition appears to be substrate independent in nature. Shown to selectively kill human osteosarcoma (U2OS) and other cancer cells, but display much reduced cytotoxicity towards several primary cells. Causes incorporation of oxidized dNTPs into cancer cells, leading to cytotoxic DNA damage, independent of their p53 status. However, it can also trigger ATM-p53-mediated death response and DNA repair in U2OS cells. Does not display any inhibitory activity against 87 enzymes, GPCRs, protein kinases, ion channels, and transporters even at 10 µM levels. Effectively suppresses MCF7 and SW480 tumor xenografts in mice (30 mg/kg, s.c., q.d.).

Please note that the molecular weight for this compound is batch-specific due to variable water content.

Cell permeable: yes

Primary Target
MTH1

Reversible: yes

Packaged under inert gas

Toxicity: Standard Handling (A)

Following reconstitution, aliquot and freee (-20°C). Stock solutions are stable for up to 6 months at -20°C.

Gad, H., et al. 2014. Nature508, 215.

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