Palbociclib

A potent and selective inhibitor of CDK4/6 with IC50 of 11 nM/16 nM; no inhibition for CDK2A (IC50>5 uM) ; inhibits MDA-MB453 cells with IC50 of 0.16 uM; shows antiproliferative effect against retinoblastoma (Rb) -positive tumor cells in vitro and reduces the phospho-Ser780/Ser795 on the Rb protein; orally bioavailable.Breast Cancer Approved (In Vitro) :Palbociclib (0-1 μM, 24 h) inhibits Rb Phosphorylation at Ser795 in MDA-MB-435 cells with an IC50 value of 0.063 μM, and obtains similar effects on both Ser780 and Ser795 phosphorylation in the Colo-205 colon carcinoma.Palbociclib (0-10 μM, 24 h) arrests MDA-MB-453 cells exclusively in G1 phase.Palbociclib (500 nM, 7 days) increases expression of homologous genes (H2d1, H2k1, and B2m) in MDA-MB-453 and MDA-MB-361 cells.Palbociclib (0-1 μM, 6 days) inhibits growth of several luminal ER-positive as well as HER2-amplified breast cancer cell lines, with IC50 values ranging from 4 nM to 1 μM.Palbociclib (0-1 μM, 3 days) inhibits the proliferation of human liver cancer cell lines with IC50 values ranging from 0.01 μM to 3.49 μM, and induces a reversible cell cycle arrest. (In Vivo) :Palbociclib (oral adminstration, 75 or 150 mg/kg, daily for 14 days) produces rapid tumor regressions and delays tumor growth.Palbociclib (oral adminstration, 90 mg/kg, daily for 12 days) reduces Treg numbers and the Treg:CD8 ratio in the spleen and lymph nodes in tumor-free mice, demonstrating the tumor-independent effects.Palbociclib (oral administration, 100 mg/kg, daily for 1 week) has potent antitumour effects in genetically engineered mosaic mouse model of liver cancer.