ON-123300

ON-123300 is a multi-kinase inhibitor.^1,2 It inhibits ARK5, Cdk4, and Cdk6 (IC₅₀s = 3.87, 9.82, and 4.95 nM, respectively) as well as FYN, PDGFRβ, Abl, and PI3Kδ (IC₅₀s = 11.09, 26, 53.32, and 144 nM, respectively) among others.² It inhibits proliferation in a panel of 38 cancer cell lines (GI₅₀s = 0.05-5 µM).² ON-123300 also inhibits proliferation of U87 glioma cells (IC₅₀ = 3.4 µM), decreases phosphorylation of Akt and activates ERK, as well as halts the cell cycle in the G₂/M phase and induces apoptosis.¹ When used in combination with the EGFR inhibitor gefitinib (Item No. 13166), it synergistically induces cytotoxicity of U87, U87 VIII, and U87 PTEN cells. ON-123300 reduces tumor growth in an MDA-MB-231 mouse xenograft model when administered at a dose of 50 mg/kg every other day.²

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1. Zhang, X., Lv, H., Zhou, Q., et al. Preclinical pharmacological evaluation of a novel multiple kinase inhibitor, ON123300, in brain tumor models. Mol. Cancer Ther. 13(5), 1105-1116 (2014).

2. Reddy, M.V.R., Akula, B., Conseza, S.C., et al. Discovery of 8-cyclopentyl-2-[4-(4-methyl-piperazin-1-yl)-phenylamino]-7-oxo-7,8-dihydro-pyrido[2,3-d]pyrimidine-6-carbonitrile (7x) as a potent inhibitor of cyclin-dependent kinase 4 (CDK4) and AMPK-related kinase 5 (ARK5). J. Med. Chem. 57(3), 578-599 (2014).