Palbociclib

SKU: orb1224631

Description

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.

Research Area

Pharmacology & Drug Discovery

Key Properties

• CAS Number: 571190-30-2
• MW: 447.5327
• Purity: >98% (HPLC)
• Formula: C₂₄H₂₉N₇O₂
• SMILES: CC(=O)C1=C(C)C2=CN=C(NC3=NC=C(C=C3)N3CCNCC3)N=C2N(C2CCCC2)C1=O
• Target: CDK
• Solubility: DMSO: 0.2 mg/mL (Need ultrasonic or warming)

Bioactivity

• In Vivo:
  Animal model: Mice bearing Colo-205 colon carcinoma xenografts (p16 deleted). Dosage: 75, 150 mg/kg, daily for 14 days. Administration: Oral adminstration. Result: Produced rapid tumor regressions and a corresponding tumor growth delay of ~50 days. Animal model: Tumor-free female FVB mice. Dosage: 90 mg/kg (diluted in 50 nM sodium D-lactate), daily for 12 days. Administration: Oral adminstration. 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). Dosage: 100 mg/kg, daily for 1 week. Administration: Oral adminstration. Result: Decreased the luminescence signal in liver and delayed tumour growth.
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• In Vitro:
  Cell Cycle Analysis Cell line: MDA-MB-453 cells. Concentration: 0-1 μM. Incubation time: 24 h. Result: Arrested MDA-MB-453 cells in G1.Cell Proliferation Assay Cell line: ER-positive as well as HER2-amplified breast cancer cell lines (MDA-MB-175, ZR-75-30, CAMA-1, etc. ) Concentration: 0-1 μM. Incubation time: 6 days. Result: Inhibited growth of luminal ER-positive as well as HER2-amplified breast cancer cell lines.
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Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

PD0332991 | PD-0332991 | PD 0332991

Quick Database Links

Gene Symbol

CDK