CDK4/6-IN-15 drochloride is an orally active and selective CDK4/6 inhibitor. CDK4/6-IN-15 drochloride potently inhibits cancer cells growth. CDK4/6-IN-15 drochloride arrests cell cycle at G1 phase and suppresses retinoblastoma tumour suppressor protein (Rb) phosphorylation at S780 and E2 factor (E2F)-regulated gene expression.
CDK4/6-IN-15 (compound 91) (10 μM; 24 h) also potently inhibits FLT3 and MYLK4 with inhibition rates >90%[1].CDK4/6-IN-15 (0-5 μM; 72 h) suppresses tumour cell proliferation selectively with GI50s of 0.107 μM (MV4-11) and 0.325 μM (MDA-MB-453)[1].CDK4/6-IN-15 (0.1-1 μM; 24 h) arrests exclusively the cell cycle at G1 phase in Rb-positive MV4-11 cells and MDA-MB-453 cells[1].CDK4/6-IN-15 (0.1-1 μM or 0.3-3 μM; 24-96 h) triggers apoptosis in MV4-11 and MDA-MB-453 cells[1].CDK4/6-IN-15 (0.1-3.3 μM; 4-24 h) inhibits phosphorylation of Rb[1].
CDK4/6-IN-15 (compound 91) (2 mg/kg for i.v. or 10 mg/kg for p.o.; single dose) shows comparable oral absorption in healt male adult BALB/c mice (20-25 g) as well as (5 mg/kg for i.v. or 200 mg/kg for p.o.; single dose) in male albino Wistar rats (250-350 g)[1].Pharmacokinetic Analysis[1]
References:
[1]. Tadesse S, et al. Discovery and pharmacological characterization of a novel series of highly selective inhibitors of cyclin-dependent kinases 4 and 6 as anticancer agents. Br J Pharmacol. 2018 Jun;175(12):2399-2413.