A8316-5mg | PD 0332991 (Palbociclib) HCl [827022-32-2] Clinisciences

PD-0332991 is selective and oral inhibitor of cyclin-dependent kinase 4/6 with IC50 values of 11nM and 16nM, respectively for CDK4 and CDK6 [1].

PD-0332991 is a highly specific inhibitor of CDK4/6. It is a potent anti-proliferative agent against Rb-positive tumor cells in vitro, subsequently inducing an exclusive G1 arrest. It has been reported to prevent tumor growth in disseminated human myeloma xenografts and induce G1 arrest in primary bone marrow cells [2].

PD-0332991 is also studied in breast cancer. It causes growth inhibition of ER-positive cell lines and 10/16 HER2-amplified cell lines. 100nM PD-0332991 can inhibit the phosphorylation of Rb in three more sensitive cell lines, resulting in prevention of cell cycle progression [2].

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.

1. Schwartz, Hannah, et al. "In vitro Methods to Better Evaluate Drug Responses in Cancer." UMass Chan Medical School. September 8, 2022.
2. Paula Carpintero-Fernández, Michela Borghesan, et al. "Genome wide CRISPR/Cas9 screen identifies the coagulation factor IX (F9) as a regulator of senescence." Cell Death Dis. 2022 Feb 19;13(2):163. PMID: 35184131
3. Anca Nastase, Amit Mandal, et al. "Integrated genomics point to immune vulnerabilities in pleural mesothelioma." Sci Rep. 2021 Sep 27;11(1):19138. PMID: 34580349
4. Minghui Liu, Liyuan Cui, et al. "PD-0332991 combined with cisplatin inhibits nonsmall cell lung cancer and reversal of cisplatin resistance." Thorac Cancer. 2021 Mar;12(6):924-931. PMID: 33534964
5. Anca Nastase, Amit Mandal, et al. "Multiple therapeutic pathways in malignant mesothelioma identified by genomic mapping." medRxiv. March 30, 2020.
6. Borghesan M, Fafián-Labora J, et al. "Small Extracellular Vesicles Are Key Regulators of Non-cell Autonomous Intercellular Communication in Senescence via the Interferon Protein IFITM3." Cell Rep. 2019 Jun 25;27(13):3956-3971.e6. PMID: 31242426
7. Gasset-Rosa F, Lu S, et al. "Cytoplasmic TDP-43 De-mixing Independent of Stress Granules Drives Inhibition of Nuclear Import, Loss of Nuclear TDP-43, and Cell Death." Neuron. 2019 Apr 17;102(2):339-357.e7. PMID: 30853299
8. Cheriyan VT, Alsaab H, et al. "A CARP-1 functional mimetic compound is synergistic with BRAF-targeting in non-small cell lung cancers." Oncotarget. 2018 Jul 3;9(51):29680-29697. PMID: 30038713
9. Azimi A, Caramuta S, et al. "Targeting CDK2 overcomes melanoma resistance against BRAF and Hsp90 inhibitors." Mol Syst Biol. 2018 Mar 5;14(3):e7858. PMID: 29507054
10. Yuan J, Jiang YY, et al. "Super-Enhancers Promote Transcriptional Dysregulation in Nasopharyngeal Carcinoma." Cancer Res. 2017 Dec 1;77(23):6614-6626. PMID: 28951465
11. Ma Y, Walsh MJ, et al. "CRISPR/Cas9 Screens Reveal Epstein-Barr Virus-Transformed B Cell Host Dependency Factors." Cell Host Microbe.2017 May 10;21(5):580-591.e7. PMID: 28494239

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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]
Cell lines	MDA-MB-453 cells
Preparation method	The solubility of this compound in DMSO is
Reaction Conditions	80 nM, 24 hours
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]
Animal models	Mice bearing Colo-205 colon carcinoma xenografts
Dosage form	Oral administration, 150 or 75 mg/kg, daily for 14 days
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.
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.
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.

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