ON-123300

Description	in 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.
Pathways	Cell Cycle/DNA Damage
Targets	CDK

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