ON123300

• CAT Number: I001387
• CAS Number: 1357470-29-1
• Molecular Formula: C24H27N7O
• Molecular Weight: 429.5
• Purity: ≥95%
• Target: Cyclin-Dependent Kinases
• Solubility: 10 mM in DMSO
• Storage: Store at -20°C
• IC50: 3.8 nM [1]
• InChI: 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)
• InChIKey: VADOZMZXXRBXNY-UHFFFAOYSA-N
• SMILES: CN1CCN(C2=CC=C(NC3=NC(N(C4CCCC4)C(C(C#N)=C5)=O)=C5C=N3)C=C2)CC1

ON123300 is a potent inhibitor of CDK4, with an IC50 of 3.8 nM, with little inhibitory activity against CDKs 1,2,5 and 8.IC50 value: 3.8 nM [1]Target: CDK4in vitro: ON123300 is a novel kinase inhibitor, inhibits CDK4/6 and PI3K-δ and exhibits potent activity against mantle cell lymphomas (MCLs). [1] ON123300 is a low molecular weight multi-kinase inhibitor identified through a series of screens that supported further analyses for brain tumor chemotherapy. Biochemical assays indicated ON123300 was a strong inhibitor of Ark5 and CDK4 as well as growth factor receptor tyrosine kinases such as Beta-type platelet-derived growth factor receptor [PDGFRβ]. ON123300 inhibited U87 glioma cell proliferation with an IC50 = 3.4 ± 0.1 μM and reduced phosphorylation of Akt, yet it also unexpectedly induced Erk activation; both in a dose- and time-dependent manner that subsequently was attributed to relieving Akt-mediated C-Raf S259 inactivation and activating a p70S6K initiated PI3K negative feedback loop. [3]

Reference

1:Dual Targeting of CDK4 and ARK5 Using a Novel Kinase Inhibitor ON123300 Exerts Potent Anticancer Activity against Multiple Myeloma. Perumal D, Kuo PY, Leshchenko VV, Jiang Z, Divakar SK, Cho HJ, Chari A, Brody J, Reddy MV, Zhang W, Reddy EP, Jagannath S, Parekh S.Cancer Res. 2016 Mar 1;76(5):1225-36. doi: 10.1158/0008-5472.CAN-15-2934. Epub 2016 Feb 12. PMID: 26873845 Free Article2:Dual inhibition of CDK4/Rb and PI3K/AKT/mTOR pathways by ON123300 induces synthetic lethality in mantle cell lymphomas. Divakar SK, Ramana Reddy MV, Cosenza SC, Baker SJ, Perumal D, Antonelli AC, Brody J, Akula B, Parekh S, Reddy EP.Leukemia. 2016 Jan;30(1):86-93. doi: 10.1038/leu.2015.185. Epub 2015 Jul 15. PMID: 26174628 Free PMC Article3:Preclinical pharmacological evaluation of a novel multiple kinase inhibitor, ON123300, in brain tumor models. Zhang X, Lv H, Zhou Q, Elkholi R, Chipuk JE, Reddy MV, Reddy EP, Gallo JM.Mol Cancer Ther. 2014 May;13(5):1105-16. doi: 10.1158/1535-7163.MCT-13-0847. Epub 2014 Feb 25. PMID: 24568969 Free PMC Article