| Identification | Back Directory | [Name]
6-Acetyl-8-cyclopentyl-5-methyl-2-[[5-(1-piperazinyl)-2-pyridinyl]amino]pyrido[2,3-d]pyrimidin-7(8H)-one hydrochloride | [Synonyms]
PD 0332991 hydrochloride - Palbociclib hydrochloride
6-Acetyl-8-cyclopentyl-5-methyl-2-(5-piperazin-1-yl-pyridin-2-ylamino)-8H-pyrido[2,3-d]pyrimidin-7-one dihydrochloride
6-Acetyl-8-cyclopentyl-5-methyl-2-[[5-(1-piperazinyl)-2-pyridinyl]amino]pyrido[2,3-d]pyrimidin-7(8H)-one hydrochloride
6-Acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one hydrochloride (20:37) | [MDL Number]
MFCD18089822 | [MOL File]
571189-11-2.mol |
| Hazard Information | Back Directory | [Uses]
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]. | [in vivo]
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]. | Animal Model: | Mice bearing Colo-205 colon carcinoma xenografts (p16 deleted)[1] | | Dosage: | 75, 150 mg/kg | | Administration: | Oral administration; daily for 14 days | | Result: | Produced rapid tumor regressions and a corresponding tumor growth delay of ~50 days. |
| Animal Model: | Tumor-free female FVB mice[2] | | Dosage: | 90 mg/kg | | Administration: | Oral administration; daily for 12 days | | Result: | Reduced total thymic mass and immature CD4+ and CD8+ double-positive thymocytes, and increased the fractions of CD4+ and CD8+ single-positive thymocytes. |
| Animal Model: | Genetically engineered mosaic mouse model of liver cancer (Myc;p53-sgRNA)[4] | | Dosage: | 100 mg/kg | | Administration: | Oral administration; daily for 1 week | | Result: | Decreased the luminescence signal in liver and delayed tumour growth. |
| [IC 50]
DYRK1A: 2000 nM (IC50); MAPK: 8000 nM (IC50); Cdk4/cyclin D3: 9 nM (IC50); Cdk4/cyclin D1: 11 nM (IC50); Cdk6/cyclin D2: 16 nM (IC50) | [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. PMID:15542782
[2] Goel S, et al. CDK4/6 inhibition triggers anti-tumour immunity. Nature. 2017 Aug 24;548(7668):471-475. DOI:10.1038/nature23465
[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. DOI:10.1186/bcr2419
[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. DOI:10.1136/gutjnl-2016-312268 |
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| Company Name: |
Axon Medchem BV
|
| Tel: |
+31-50-3118007 |
| Website: |
www.axonmedchem.com |
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