BAY-707, a highly potent and selective substrate-competitive inhibitor of MTH1 (NUDT1) with an IC50 of 2.3 nM, is well-tolerated in mice and exhibits a favorable pharmacokinetic (PK) profile compared to other MTH1 compounds. However, it demonstrates a clear lack of anticancer efficacy both in vitro and in vivo[1].

MTH1/NUDT1:2.3 nM

BAY-707 demonstrates a superior cellular target engagement with an EC50 of 7.6 nM, in agreement with its higher enzymatic potency (IC50=2.3 nM)[1] and it also demonstrates a high cell permeability cell permeability in the Caco-2 assay with a efflux ratio of 288 nm/s[1]. BAY-707 (0-30 μM; 24 hours) has no antiproliferative effects in HMEC, HeLa and SW-480 cells[1]. BAY-707 shows an overall favorable physicochemical profile and promising?in vitro?pharmacokinetic properties with high metabolic stability in both human microsomes(0.29L/h/kg,Fmax=78%) and rat hepatocytes (0.54L/h/kg,Fmax=87%)[1].

BAY-707 (orally adminstation; 50-250 mg/kg; 2 weeks) is well-tolerated in nude mice, after 7-days treatment, body weight loss does not exceed 10% [1] and it also exhibits superior biochemical potency, cellular target engagement, and a pharmacokinetic profile to other MTH1 tool compounds. However, Bay-077 exerts no anticancer efficacy either in mono- or in combination therapies in CT26 and NCI-H460 mice model[1].