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ON-123300 is a multi-kinase inhibitor. It inhibits ARK5, Cdk4, and Cdk6 (IC50s = 3.87, 9.82, and 4.95 nM, respectively) as well as FYN, PDGFRbeta, Abl, and PI3Kdelta (IC50s = 11.09, 26, 53.32, and 144 nM, respectively) among others. It inhibits proliferation in a panel of 38 cancer cell lines (GI50s = 0.05-5 µM). 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. When used in combination with the EGFR inhibitor gefitinib (Cay-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.Formal Name: 8-cyclopentyl-7,8-dihydro-2-[[4-(4-methyl-1-piperazinyl)phenyl]amino]-7-oxo-pyrido[2,3-d]pyrimidine-6-carbonitrile. CAS Number: 1357470-29-1. Molecular Formula: C24H27N7O. Formula Weight: 429.5. Purity: >98%. Formulation: (Request formulation change), A crystalline solid. Solubility: DMF: 16 mg/mL, DMF:PBS(pH7.2) (1:2): 0.3 mg/mL, DMSO: 10 mg/mL, Ethanol: 0.25 mg/mL. lambdamax: 224, 269, 315, 392 nm. SMILES: CN1CCN(C2=CC=C(NC3=NC(N(C4CCCC4)C(C(C#N)=C5)=O)=C5C=N3)C=C2)CC1. InChi Code: InChI=1S/C24H27N7O/c1-29-10-12-30(13-11-29)20-8-6-19(7-9-20)27-24-26-16-18-14-17(15-25)23(32)31(22(18)28-24)21-4-2-3-5-21/h6-9,14,16,21H,2-5,10-13H2,1H3,(H,26,27,28). InChi Key: VADOZMZXXRBXNY-UHFFFAOYSA-N.
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