PD 0332991 (Palbociclib) HCl
PD 0332991 (Palbociclib) HCl (CAS 827022-32-2) is a selective, orally bioavailable inhibitor targeting cyclin-dependent kinases 4 and 6 (CDK4/6). By inhibiting CDK4/6, PD 0332991 prevents phosphorylation of retinoblastoma (Rb) protein, thereby inducing cell cycle arrest at the G1 phase. It exhibits inhibitory activity against CDK4 and CDK6 with IC50 values of 11 nM and 16 nM, respectively. PD 0332991 demonstrates antiproliferative activity in Rb-positive tumor cells, suppressing tumor growth and promoting G1 arrest in models of multiple myeloma and ER-positive/HER2-amplified breast cancer cell lines.
References:
[1] Ivan Diaz-Padilla, Lillian L. Siu and Ignacio Duran. Cyclin-dependent kinase inhibitors as potential targeted anticancer agents. Invest New Drugs. 2009, 27: 586–594.
[2] Richard S Finn, Judy Dering, Dylan Conklin, Ondrej Kalous, David J Cohen, Amrita J Desai, Charles Ginther, Mohammad Atefi, Isan Chen, Camilla Fowst, Gerret Los and Dennis J Slamon. 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 Research. 2009, 11: R77.
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| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 483.99 |
| Cas No. | 827022-32-2 |
| Formula | C24H30ClN7O2 |
| Synonyms | PD0332991; PD-0332991; PD 0332991 |
| Solubility | ≥14.48 mg/mL in H2O; ≥2.42 mg/mL in DMSO; ≥2.79 mg/mL in EtOH with gentle warming and ultrasonic |
| Chemical Name | 6-acetyl-8-cyclopentyl-5-methyl-2-((5-(piperazin-1-yl)pyridin-2-yl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one hydrochloride |
| SDF | Download SDF |
| Canonical SMILES | O=C1N(C2=NC(NC3=NC=C(C=C3)N4CCNCC4)=NC=C2C(C)=C1C(C)=O)C5CCCC5.Cl |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Cell experiment: [1] | |
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Cell lines |
MDA-MB-453 cells |
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Preparation method |
The solubility of this compound in DMSO is |
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Reaction Conditions |
80 nM, 24 hours |
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Applications |
MDA-MB-453 breast carcinoma cells exposed to varying concentrations of PD 0332991 for 24 hours showed a significant increase in the percentage of cells in G1 in the presence of as little as 0.04 μmol/L PD 0332991 with a concomitant decline in other phases of the cell cycle. Maximum effects were attained at 0.08 μmol/L and an exclusive G1 arrest was maintained even at concentrations as high as 10 μmol/L, consistent with the complete absence of any other effects on the cell cycle. |
| Animal experiment: [1] | |
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Animal models |
Mice bearing Colo-205 colon carcinoma xenografts |
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Dosage form |
Oral administration, 150 or 75 mg/kg, daily for 14 days |
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Applications |
Administration of PD 0332991 produced rapid tumor regressions and a corresponding tumor growth delay of about 50 days with >1 log of tumor cell kill at the highest dose tested. At 37.5 mg/kg, the tumor slowly regressed during treatment. Even at doses as low as 12.5 mg/kg, a 13 day growth delay was obtained indicating a 90% inhibition of tumor growth rate. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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References: [1] Fry D W, Harvey P J, Keller P R, et al. Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts. Molecular cancer therapeutics, 2004, 3(11): 1427-1438. |
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| Description | Palbociclib (PD-0332991) HCl is a highly selective inhibitor of CDK4/6 with IC50 of 11 nM/16 nM. | |||||
| Targets | CDK4/cyclin D1 | CDK6/cyclin D2 | ||||
| IC50 | 11 nM | 16 nM | ||||
Quality Control & MSDS
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