Palbociclib hydrochloride

• CAT Number: I046415
• CAS Number: 571189-11-2
• Molecular Formula: C24H30ClN7O2
• Molecular Weight: 514.99
• Purity: ≥95%
• Synonyms: 6-acetyl-8-cyclopentyl-5-methyl-2-[(5-piperazin-1-ylpyridin-2-yl)amino]pyrido[2,3-d]pyrimidin-7-one;hydrochloride
• InChI: InChI=1S/C24H29N7O2.ClH/c1-15-19-14-27-24(28-20-8-7-18(13-26-20)30-11-9-25-10-12-30)29-22(19)31(17-5-3-4-6-17)23(33)21(15)16(2)32;/h7-8,13-14,17,25H,3-6,9-12H2,1-2H3,(H,26,27,28,29);1H
• InChIKey: STEQOHNDWONVIF-UHFFFAOYSA-N
• SMILES: CC1=C(C(=O)N(C2=NC(=NC=C12)NC3=NC=C(C=C3)N4CCNCC4)C5CCCC5)C(=O)C.Cl

Palbociclib (PD 0332991) hydrochloride is an orally active selective CDK4 and CDK6 inhibitor with IC50 values of 11 and 16 nM, respectively. Palbociclib hydrochloride has potent anti-proliferative activity and induces cell cycle arrest in cancer cells. Palbociclib hydrochloride can be used in the research of HR-positive and HER2-negative breast cancer and hepatocellular carcinoma[1][3][4].
Palbociclib (0-1 μM, 24 h) hydrochloride 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) hydrochloride arrests MDA-MB-453 cells exclusively in G1 phase[1].
Palbociclib (500 nM, 7 days) hydrochloride 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) hydrochloride 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) hydrochloride 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) hydrochloride produces rapid tumor regressions and delays tumor growth[1].
Palbociclib (oral adminstration, 90 mg/kg, daily for 12 days) hydrochloride 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) hydrochloride has potent antitumour effects in genetically engineered mosaic mouse model of liver cancer[4].

Reference

[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.
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[2]. Goel S, et al. CDK4/6 inhibition triggers anti-tumour immunity. Nature. 2017 Aug 24;548(7668):471-475.
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[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.
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[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.
 [Content Brief]