Palbociclib (PD0332991) Isethionate
Licensed and Manufactured by Pfizer Catalog No.S1579
Molecular Weight(MW): 573.66
Palbociclib (PD0332991) Isethionate is a highly selective inhibitor of CDK4/6 with IC50 of 11 nM/16 nM in cell-free assays. It shows no activity against CDK1/2/5, EGFR, FGFR, PDGFR, InsR, etc. Phase 3.
Cited by 13 Publications
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(C) In vivo treatment of Tg:Pomc-Pttg;Pomc-eGFP embryos with small-molecule CDK inhibitors (50μM) or 0.2% DMSO as control from 18 to 40 hpf. One hundred to one hundred fifty embryos were treated with each compound. Representative images of live embryos are shown with gross morphology (Right) and pituitary Pomc-GFP–positive cells at higher magnification (Left) at 40 hpf. Embryos exposed to flavopiridol developed early developmental defect before pituitary POMC cell ontogeny occurs. (D) Relative expression of pituitary Pomc-eGFP fluorescence analyzed using Volocity 5.2 software (Improvision; mean ±SE of relative expression, n = 7). (E) R-roscovitine specifically suppresses expansion of pituitary POMC cells overexpressing zPttg from 18 to 48 hpf. Double transgenic Tg:Pomc-Pttg;Prl-RFP embryos were generated by breeding Tg:Pomc-Pttg fish with a previously generated PRL-RFP transgenic line, in which RFP was targeted to pituitary lactotrophs by a zebrafish Prolactin promoter (34). Representative fluorescent microscopy of pituitary POMC-eGFP (a and b) and PRL-RFP (c and d) expression in live Tg:Pomc-Pttg; Pomc-eGFP and Tg:Pomc-Pttg;Prl-RFP embryos treated with 0.2% DMSO (a and c) or 50 μM R-roscovitine (b and d). (F) Relative expression of pituitary POMC-eGFP or PRL-RFP fluorescence were analyzed (mean ±SE of relative expression; n = 10). Results represent one of three similar experiments;*P < 0.02 and **P < 0.000005. (Scale bar, 50 μm.)
PNAS 2011 108(20), 8414-9. Palbociclib (PD0332991) Isethionate purchased from Selleck.
Potentiation of SFN-induced cytotoxicity by a panel of CDK inhibitors in MDA-MB-231 cells. The fraction of cells killed (Fa ±SEM) by SFN in the presence of DMSO (vehicle) or a fixed concentration (0.2 uM) of PD0332991. The fraction of cells killed by CDK inhibitors at a fixed concentration of 0.2 uM is shown for comparison [dashed lines; gray shading (±SEM)]. MDE-CI analysis of drug interactions in the upper panels. CIs as a function of SFN concentration are shown. Black, gray, and white bars denote synergistic (CI < 0.9), additive (CI = 0.9-1.1), or antagonistic interactions (CI > 1.1), respectively. Synergistic ratios and SFN-EC50 are indicated. Data are representative of two to three independent experiments.
Neoplasia 2013 15(8), 939-51. Palbociclib (PD0332991) Isethionate purchased from Selleck.
HT29 cells were treated with DMSO control, 1 uM selumetinib (Sel) or 5 uM PD0332991 (991) for 24 or 48 h after which time cells were lysed, subjected to SDS/PAGE and immunoblotted with the indicated antibodies.
Biochem J 2014 459(3), 513-24. Palbociclib (PD0332991) Isethionate purchased from Selleck.
Patient tumor cell sensitivity to combinatorial treatment with histone deacetylase (HDAC)/cyclin-dependent kinase (CDK) inhibitors in 3-D culture. The effect of each drug or drug combination was assessed by fluorescent dye to identify live (green) and dead cells (red). Cells from breast reduction patients were used as non-cancer control in the assay.
Pharmacogenomics J 2013 13(1), 94-104. Palbociclib (PD0332991) Isethionate purchased from Selleck.
Immunoblot analysis of PD0332991-induced senescence in MEL10 cells. Cells were treated with indicated concentrations of PD0332991 with or without 10 nM rapamycin. After 1 day, cells were lysed and immunoblotting was performed with the indicated antibodies.
Cell Cycle 2013 12(18), 3063-9. Palbociclib (PD0332991) Isethionate purchased from Selleck.
Western blot analysis shows inhibition of Rb phosphorylation at the protein level, with inhibition of PD-0332991 observed at 2uM in the PDGF-B; Ink4a-ARF deficient line after only 24 hours of treatment.
PLoS One 2013 8(10), e77639. Palbociclib (PD0332991) Isethionate purchased from Selleck.
Cdk4 is upregulated in ARMS and mMSCs transfected with PAX7-FKHR fusion gene (MP7F), and can be specifi cally inhibited. D: IF results showing overexpression of cdk4 in MP7F cells compared to parental mMSCs and reduced expression of cdk4 after treatment of MP7F cells with the cdk4 inhibitor, PD-0332991. E: IF results showing MyoD1 expression in parental mMSCs cells, and MP7F cells untreated and after treatment with the cdk4 inhibitor, PD-0332991.
Clin Transl Oncol 2012 14(3), 197-206 . Palbociclib (PD0332991) Isethionate purchased from Selleck.
Different breast cancer cell lines were seeded in 96 well plates and treated with different concentrations of PD0332991. After 72h, cell viability was assessed by MTT. Data shows that these cancer cell lines had a better response to CDK4/6 inhibition than the less tumorigenic MCF10A-Ras cells.
Helen Sadik from Johhns Hopkins University. Palbociclib (PD0332991) Isethionate purchased from Selleck.
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Choose Selective CDK Inhibitors
|Description||Palbociclib (PD0332991) Isethionate is a highly selective inhibitor of CDK4/6 with IC50 of 11 nM/16 nM in cell-free assays. It shows no activity against CDK1/2/5, EGFR, FGFR, PDGFR, InsR, etc. Phase 3.|
|Features||The 1st specific inhibitor for CDK4/6 to show promise in multiple cancers.|
PD 0332991 exhibits absolute selectivity for CDK4/6 with little or no activity against other CDKs. PD 0332991 is effective at reducing Rb phosphorylation at Ser780 and Ser795 in MDA-MB-435 breast carcinoma cells with IC50 of 66 nM and 63 nM, respectively. PD 0332991 is a potent inhibitor of cell growth and suppresses DNA replication by preventing cells from entering S phase. PD 0332991 inhibits thymidine incorporation into the DNA of Rb-positive human breast (such as MDA-MB-435, MCF-7), colon (H1299), and lung carcinomas (Colo-205) as well as human leukemias (CRRF-CEM and K562), with IC50 values ranging from 0.04-0.17 μM. PD 0332991 significant increases the percentage of MDA-MB-453 in G1 period.  PD 0332991 inhibits phosphorylation of Rb in cycling CD138+ primary bone marrow myeloma cells, nontransformed primary B cells, MM1.S and CAG HMCLs cells line with IC50 of <0.1 μM, 0.05 μM, and 60-70 nM, respectively. PD 0332991 treatment also induces G1 arrest of CD138+ primary bone marrow myeloma and nontransformed primary B cells. PD 0332991 induces G1 arrest in MM1.S with IC50 of ~0.05 μM.  PD 0332991 preferentially inhibits proliferation of luminal estrogen receptor-positive (including HER2-positive) human breast cancer cell lines. PD 0332991 increases gene expression of pRb and cyclin D1 and decreases gene expression of CDKN2A (p16) in most sensitive lines. PD 0332991 enhances sensitivity to tamoxifen in cell lines with conditioned resistance to ER blockade. 
|In vivo||PD 0332991(150 mg/kg) produces rapid Colo-205 colon carcinoma xenografts regressions and a corresponding tumor growth delay. PD 0332991 (150 mg/kg) induces complete tumor stasis and cell kill in MDA-MB-435 breast carcinoma. PD 0332991 (150 mg/kg) also induces significant tumor regression in mice bearing the SF-295 glioblastoma xenografts, and in ZR-75-1 breast and PC-3 prostate tumor models (complete suppression of tumor growth). PD 0332991 (150 mg/kg) suppresses Rb Ser780 phosphorylation in MDA-MB-435 breast carcinoma over the full 24-hour period. PD 0332991 (150 mg/kg) down-regulates expression of four E2F-regulated genes CDC2, CCNE2, TK1, and TOP2A in Colo-205 carcinoma xenografts.  PD 0332991 also rapidly inhibits myeloma tumor growth. |
CDK activity assays:CDK assays for IC50 determinations and kinetic evaluation are performed in 96-well filter plates. All CDK-cyclin kinase complexes are expressed in insect cells through baculovirus infection and purified. The substrate for the assays is a fragment (amino acids 792–928) of pRb fused to GST (GST•RB-Cterm). The total reaction volume is 0.1 mL containing a final concentration of 20 mM Tris-HCl, pH 7.4, 50 mM NaCl, 1 mM dithiothreitol, 10 mM MgCl2 25 μM ATP (for CDK4-cyclin D1, CDK6-cyclin D2, and CDK6-cyclin D3) containing 0.25 μCi of [γ-32P]ATP, 20 ng of enzyme, 1 μg of GST•RB-Cterm, and appropriate dilutions of inhibitor. All components except the [γ-32P]ATP are added to the wells, and placed on a plate mixer for 2 min. The reaction is started by adding the [γ-32P]ATP, and incubated at 25℃ for 15 min. The reaction is terminated by addition of 0.1 mL of 20% trichloroacetic acid, and the plate is kept at 4 ℃ for at least 1 hr to allow the substrate to precipitate. The wells are then washed five times with 0.2 mL of 10% trichloroacetic acid, and radioactive incorporation is determined with a β plate counter.
|In vitro||Water||10 mg/mL warmed (17.43 mM)|
|In vivo||Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
saline (with warming)
For best results, use promptly after mixing.
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Clinical Trial Information
|NCT Number||Recruitment||Conditions||Sponsor/Collaborators||Start Date||Phases|
|NCT03709680||Not yet recruiting||Solid Tumors|Ewing Sarcoma|Rhabdoid Tumor|Rhabdomyosarcoma|Neuroblastoma|Medulloblastoma||Pfizer||February 5 2019||Phase 1|
|NCT03609047||Not yet recruiting||Breast Cancer Stage II|Breast Cancer Stage III||European Organisation for Research and Treatment of Cancer - EORTC|Pfizer||January 7 2019||Phase 2|
|NCT03691493||Not yet recruiting||Anatomic Stage IV Breast Cancer AJCC v8|Estrogen Receptor Positive|HER2/Neu Negative|Metastatic Breast Carcinoma|Metastatic Malignant Neoplasm in the Bone|Progesterone Receptor Positive|Prognostic Stage IV Breast Cancer AJCC v8||Emory University|Pfizer||December 1 2018||Phase 2|
|NCT03530696||Not yet recruiting||HER2-positive Breast Cancer|Breast Cancer|Breast Cancer Stage|Recurrent Breast Cancer|Metastatic Breast Cancer|HER2 Positive Breast Carcinoma||University of Arizona|Pfizer||November 30 2018||Phase 2|
|NCT03531645||Not yet recruiting||Malignant Neoplasms of Female Genital Organs||M.D. Anderson Cancer Center|AstraZeneca|Pfizer||November 2018||Phase 2|
|NCT03535506||Recruiting||DCIS||Georgetown University|Pfizer||October 8 2018||Phase 2|
Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.
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Frequently Asked Questions
What is the best vehicle for palbociclib for in vitro and in vivo?
You can use water for vitro use and Saline for vivo use.