ON123300

1357470-29-1

429.52

DMSO : 16.67 mg/mL (38.81 mM; ultrasonic and warming and heat to 60C)

Cell Cycle/DNA Damage

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: CDK4 in vitro: ON123300 is a novel kinase inhibitor, inhibits CDK4/6 and PI3K-delta 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 [PDGFRbeta]. ON123300 inhibited U87 glioma cell proliferation with an IC50 = 3.4 +/- 0.1 uM 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]