Palbociclib (PD 0332991) drochloride is an orally active selective CDK4 and CDK6 inhibitor with IC50 values of 11 and 16 nM, respectively. Palbociclib drochloride has potent anti-proliferative activity and induces cell cycle arrest in cancer cells. Palbociclib drochloride can be used in the research of HR-positive and HER2-negative breast cancer and hepatocellular carcinoma.
Palbociclib (0-1 μM, 24 h) drochloride inhibits retinoblastoma 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[1].Palbociclib (0-10 μM, 24 h) drochloride arrests MDA-MB-453 cells exclusively in G1 phase[1].Palbociclib (500 nM, 7 days) drochloride increases expression of homologous genes (H2d1, H2k1, and B2m) in MDA-MB-453 and MDA-MB-361 cells[2].Palbociclib (0-1 μM, 6 days) drochloride 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[3].Palbociclib (0-1 μM, 3 days) drochloride 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[4].
Palbociclib (oral adminstration, 75 or 150 mg/kg, daily for 14 days) drochloride produces rapid tumor regressions and delays tumor growth[1].Palbociclib (oral adminstration, 90 mg/kg, daily for 12 days) drochloride reduces Treg numbers and the Treg:CD8 ratio in the spleen and lymph nodes in tumor-free mice, demonstrating the tumor-independent effects[2].Palbociclib (oral administration, 100 mg/kg, daily for 1 week) drochloride has potent antitumour effects in genetically engineered mosaic mouse model of liver cancer[4].
References:
[1]. Fry DW, et al. Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. Mol Cancer Ther. 2004 Nov;3(11):1427-38.
[2]. Goel S, et al. CDK4/6 inhibition triggers anti-tumour immunity. Nature. 2017 Aug 24;548(7668):471-475.
[3]. Richard S Finn, et al. PD 0332991, a selective cyclin D kinase 4/6 inhibitor, preferentially inhibits proliferation of luminal estrogen receptor-positive human breast cancer cell lines in vitro. Breast Cancer Res. 2009;11(5):R77.
[4]. Bollard J, et al. Palbociclib (PD-0332991), a selective CDK4/6 inhibitor, restricts tumour growth in preclinical models of hepatocellular carcinoma. Gut. 2017 Jul;66(7):1286-1296.