NVP-CGM097 is an inhibitor of the protein-protein interaction between murine double minute 2 (MDM2) and p53 (IC50 = 1.7 nM for human MDM2 in a TR-FRET assay).1 It is selective for human MDM2 (Ki = 1.3 nM) over dog, mouse, and rat Mdm2 (Kis = 20.5, 65.9, and 47.4 nM, respectively).2 NVP-CGM097 selectively inhibits proliferation of acute myeloid leukemia (AML) cells expressing wild-type p53 (IC50s = 50-1,000 nM) over AML cells expressing mutant p53 (IC50s = >1,000 nM).1 It induces tumor regression in a patient-derived xenograft (PDX) mouse model of AML when administered at a dose of 100 mg/kg per day.1
1.Weisberg, E., Halilovic, E., Cooke, V.G., et al.Inhibition of wild-type p53-expressing AML by the novel small molecule HDM2 inhibitor CGM097Mol. Cancer Ther.14(10)2249-2259(2015) 2.Holzer, P., Masuya, K., Furet, P., et al.Discovery of a dihydroisoquinolinone derivative (NVP-CGM097): A highly potent and selective MDM2 inhibitor undergoing phase 1 clinical trials in p53wt tumorsJ. Med. Chem.58(16)6348-6358(2015)