IC50:2.3 nM (MTH1/NUDT1)

BAY-707 demonstrates a superior cellular target engagement with an EC ₅₀ of 7.6 nM, in agreement with its higher enzymatic potency (IC ₅₀ =2.3 nM). BAY-707 demonstrates a high cell permeability cell permeability in the Caco-2 assay with a efflux ratio of 288 nm/s. 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,F _max =78%) and rat hepatocytes (0.54L/h/kg,F _max =87%) . BAY-707 (0-30 μM; 24 hours) has no antiproliferative effects in HMEC, HeLa and SW-480 cells.

Bay-077 (orally adminstation; 50-250 mg/kg; 2 weeks) exhibits superior biochemical potency, cellular target engagement, and a pharmacokinetic profile to other MTH1 tool compounds, But Bay-077 exerts no anticancer efficacy either in mono- or in combination therapies in CT26 and NCI-H460 mice model. 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% .