[CAS NO. 1357470-29-1]  ON123300

ON123300 inhibits U87 glioma cell proliferation with an IC50 3.4±0.1 μmol/L and reduces phosphorylation of Akt, yet it also unexpectedly induces Erk activation, both in a dose- and time-dependent manner that subsequently is attributed to relieving Akt mediated C-Raf S259 inactivation and activating a p70S6K-initiated PI3K-negative feedback loop. ON123300 also inhibits CDK4/6 and PI3K-δ and exhibits potent activity against mantle cell lymphomas (MCLs). 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. MCL cell lines treated with ON123300 accumulate in the G1 phase at lower concentrations (0.1-1.0μM), at higher concentrations of the compound, a large proportion of the cells progress through the S and G2/M phases of the cell cycle and eventually accumulate in the sub-G1 phase, suggesting an induction of apoptosis. ON123300 also inhibits the phosphorylation of pRb and p130 in a dose-dependent manner. ON123300 treatment results in inhibition of FOXO1 phosphorylation, a target of mTOR.