Lerociclib

Lerociclib is an inhibitor of cyclin-dependent kinase 4 (Cdk4) and Cdk6 (IC50s = 1 and 2 nM for Cdk4/cyclin D1 and Cdk6/cyclin D3, respectively). It is selective for Cdk4 and Cdk6 over seven related Cdks, including Cdk9/cyclin T, Cdk5/p25, and Cdk1/cyclin B1 (IC50s = 28, 1,200, and 2,400 nM, respectively). Lerociclib induces cell cycle arrest at the G1 phase in WM266-4 melanoma cells (EC50 = ~20 nM). It selectively inhibits the proliferation of a variety of cancer cells expressing retinoblastoma protein (Rb) over non-Rb-expressing cancer cells (EC50s = 23-784 and 2,691->10,000 nM, respectively). Lerociclib reduces intratumoral levels of phosphorylated Rb (pRb) in an MCF-7 mouse xenograft model when administered as a single dose of 100 mg/kg and inhibits tumor growth in the same model at doses ranging from 10 to 100 mg/kg in the diet for 28 days. InChI: InChI=1S/C26H34N8O/c1-18(2)32-10-12-33(13-11-32)20-6-7-22(27-16-20)30-25-28-15-19-14-21-24(35)29-17-26(8-4-3-5-9-26)34(21)23(19)31-25/h6-7,14-16,18H,3-5,8-13,17H2,1-2H3,(H,29,35)(H,27,28,30,31), InChIKey: YPJRHEKCFKOVRT-UHFFFAOYSA-N, SMILES: O=C1C(N2C3(CN1)CCCCC3)=CC(C=N4)=C2N=C4NC(N=C5)=CC=C5N6CCN(CC6)C(C)C