BAY-707

• CAT Number: I017483
• CAS Number: 2109805-96-9
• Molecular Formula: C15H20N4O2
• Molecular Weight: 288.34
• Purity: ≥95%
• Synonyms: N-ethyl-4-[(3S)-3-methylmorpholin-4-yl]-1H-pyrrolo[2,3-b]pyridine-2-carboxamide
• InChI: InChI=1S/C15H20N4O2/c1-3-16-15(20)12-8-11-13(4-5-17-14(11)18-12)19-6-7-21-9-10(19)2/h4-5,8,10H,3,6-7,9H2,1-2H3,(H,16,20)(H,17,18)/t10-/m0/s1
• InChIKey: RPMGXDCRCWWCRY-JTQLQIEISA-N
• SMILES: CCNC(=O)C1=CC2=C(C=CN=C2N1)N3CCOCC3C

BAY-707 is a substrate-competitive, highly potent and selective inhibitor of MTH1(NUDT1) with an IC50 of 2.3 nM. BAY-707 has a good pharmacokinetic (PK) profile to other MTH1 compounds and is well-tolerated in mice, but shows a clear lack of in vitro or in vivo anticancer efficacy[1].
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].
BAY-707 demonstrates a high cell permeability cell permeability in the Caco-2 assay with a efflux ratio of 288 nm/s[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 (0-30 μM; 24 hours) has no antiproliferative effects in HMEC, HeLa and SW-480 cells[1].
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[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].

Reference

[1]. Ellermann M, et al. Novel Class of Potent and Cellularly Active Inhibitors Devalidates MTH1 as Broad-Spectrum Cancer Target.ACS Chem Biol. 2017 Aug 18;12(8):1986-1992.
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