571190-30-2 | Pd-0332991

Availability
Typically In Stock

Description

• Catalog Number: AB47813
• Chemical Name: Pd-0332991
• CAS Number: 571190-30-2
• Molecular Formula: C24H29N7O2
• Molecular Weight: 447.5328
• MDL Number: MFCD11840850
• SMILES: CC(=O)c1c(C)c2cnc(nc2n(c1=O)C1CCCC1)Nc1ccc(cn1)N1CCNCC1

Computed Properties

• Complexity: 775
• Covalently-Bonded Unit Count: 1
• Heavy Atom Count: 33
• Hydrogen Bond Acceptor Count: 8
• Hydrogen Bond Donor Count: 2
• Rotatable Bond Count: 5
• XLogP3: 1.8

Literature

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• Palbociclib treatment of FLT3-ITD+ AML cells uncovers a kinase-dependent transcriptional regulation of FLT3 and PIM1 by CDK6.

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• Brain Exposure of Two Selective Dual CDK4 and CDK6 Inhibitors and the Antitumor Activity of CDK4 and CDK6 Inhibition in Combination with Temozolomide in an Intracranial Glioblastoma Xenograft.

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• The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study.

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• CDK4/6 and IGF1 receptor inhibitors synergize to suppress the growth of p16INK4A-deficient pancreatic cancers.

  Cancer research 20140715

• Loss of CDKN2A expression is a frequent event in primary invasive melanoma and correlates with sensitivity to the CDK4/6 inhibitor PD0332991 in melanoma cell lines.

  Pigment cell & melanoma research 20140701

• CDK4/6 inhibition provides a potent adjunct to Her2-targeted therapies in preclinical breast cancer models.

  Genes & cancer 20140701

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• Synergism of cyclin-dependent kinase inhibitors with camptothecin derivatives in small cell lung cancer cell lines.

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• Targeting cell cycle and hormone receptor pathways in cancer.

  Oncogene 20131128

• Fulvestrant induces resistance by modulating GPER and CDK6 expression: implication of methyltransferases, deacetylases and the hSWI/SNF chromatin remodelling complex.

  British journal of cancer 20131112

• Identification of potent Yes1 kinase inhibitors using a library screening approach.

  Bioorganic & medicinal chemistry letters 20130801

• PD-0332991, a potent and selective inhibitor of cyclin-dependent kinase 4/6, demonstrates inhibition of proliferation in renal cell carcinoma at nanomolar concentrations and molecular markers predict for sensitivity.

  Anticancer research 20130801

• A CDK4/6 inhibitor enhances cytotoxicity of paclitaxel in lung adenocarcinoma cells harboring mutant KRAS as well as wild-type KRAS.

  Cancer biology & therapy 20130701

• Induction of prolonged early G1 arrest by CDK4/CDK6 inhibition reprograms lymphoma cells for durable PI3Kδ inhibition through PIK3IP1.

  Cell cycle (Georgetown, Tex.) 20130615

• Phase II trial of the CDK4 inhibitor PD0332991 in patients with advanced CDK4-amplified well-differentiated or dedifferentiated liposarcoma.

  Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20130601

• Inhibition of cyclin-dependent kinase 6 suppresses cell proliferation and enhances radiation sensitivity in medulloblastoma cells.

  Journal of neuro-oncology 20130101

• PD-0332991, a CDK4/6 inhibitor, significantly prolongs survival in a genetically engineered mouse model of brainstem glioma.

  PloS one 20130101

• The requirement for cyclin D function in tumor maintenance.

  Cancer cell 20121016

• Therapeutic targeting of the cyclin D3:CDK4/6 complex in T cell leukemia.

  Cancer cell 20121016

• Cdk4/6 inhibition induces epithelial-mesenchymal transition and enhances invasiveness in pancreatic cancer cells.

  Molecular cancer therapeutics 20121001

• Attenuation of the retinoblastoma pathway in pancreatic neuroendocrine tumors due to increased cdk4/cdk6.

  Clinical cancer research : an official journal of the American Association for Cancer Research 20120901

• CDK4/6 inhibition antagonizes the cytotoxic response to anthracycline therapy.

  Cell cycle (Georgetown, Tex.) 20120715

• Therapeutic response to CDK4/6 inhibition in breast cancer defined by ex vivo analyses of human tumors.

  Cell cycle (Georgetown, Tex.) 20120715

• p16-Cdk4-Rb axis controls sensitivity to a cyclin-dependent kinase inhibitor PD0332991 in glioblastoma xenograft cells.

  Neuro-oncology 20120701

• The CDK4/6 inhibitor PD0332991 reverses epithelial dysplasia associated with abnormal activation of the cyclin-CDK-Rb pathway.

  Cancer prevention research (Philadelphia, Pa.) 20120601

• Selective CDK4/6 inhibition with tumor responses by PD0332991 in patients with mantle cell lymphoma.

  Blood 20120517

• An experimental xenograft mouse model of diffuse pontine glioma designed for therapeutic testing.

  Journal of neuro-oncology 20120501

• Discovery pharmacokinetic studies in mice using serial microsampling, dried blood spots and microbore LC-MS/MS.

  Bioanalysis 20120501

• Multiple roles of cyclin-dependent kinase 4/6 inhibitors in cancer therapy.

  Journal of the National Cancer Institute 20120321

• [(18)F]FLT-PET imaging does not always 'light up' proliferating tumor cells.

  Clinical cancer research : an official journal of the American Association for Cancer Research 20120301

• Phase I, dose-escalation trial of the oral cyclin-dependent kinase 4/6 inhibitor PD 0332991, administered using a 21-day schedule in patients with advanced cancer.

  Clinical cancer research : an official journal of the American Association for Cancer Research 20120115

• A systematic screen for CDK4/6 substrates links FOXM1 phosphorylation to senescence suppression in cancer cells.

  Cancer cell 20111115

• Retinoblastoma protein modulates the inverse relationship between cellular proliferation and elastogenesis.

  The Journal of biological chemistry 20111021

• Quantitative analysis of PD 0332991 in mouse plasma using automated micro-sample processing and microbore liquid chromatography coupled with tandem mass spectrometry.

  Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 20111001

• Sensitivity of malignant rhabdoid tumor cell lines to PD 0332991 is inversely correlated with p16 expression.

  Biochemical and biophysical research communications 20110916

• Forced expression of cyclin-dependent kinase 6 confers resistance of pro-B acute lymphocytic leukemia to Gleevec treatment.

  Molecular and cellular biology 20110701

• Early G₁ cyclin-dependent kinases as prognostic markers and potential therapeutic targets in esophageal adenocarcinoma.

  Clinical cancer research : an official journal of the American Association for Cancer Research 20110701

• Phase I study of PD 0332991, a cyclin-dependent kinase inhibitor, administered in 3-week cycles (Schedule 2/1).

  British journal of cancer 20110607

• Therapeutically activating RB: reestablishing cell cycle control in endocrine therapy-resistant breast cancer.

  Endocrine-related cancer 20110601

• A bioinformatical and functional approach to identify novel strategies for chemoprevention of colorectal cancer.

  Oncogene 20110428

• Expression of p16 and retinoblastoma determines response to CDK4/6 inhibition in ovarian cancer.

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• [CDK4, a specific target in the treatment of lung adenocarcinomas mutated for KRAS].

  Medecine sciences : M/S 20101201

• Quantitative analysis of PD 0332991 in xenograft mouse tumor tissue by a 96-well supported liquid extraction format and liquid chromatography/mass spectrometry.

  Journal of pharmaceutical and biomedical analysis 20101102

• RB-pathway disruption in breast cancer: differential association with disease subtypes, disease-specific prognosis and therapeutic response.

  Cell cycle (Georgetown, Tex.) 20101015

• Toward the development of innovative bifunctional agents to induce differentiation and to promote apoptosis in leukemia: clinical candidates and perspectives.

  Journal of medicinal chemistry 20101014

• Therapeutic CDK4/6 inhibition in breast cancer: key mechanisms of response and failure.

  Oncogene 20100715

• A synthetic lethal interaction between K-Ras oncogenes and Cdk4 unveils a therapeutic strategy for non-small cell lung carcinoma.

  Cancer cell 20100713

• Pattern of retinoblastoma pathway inactivation dictates response to CDK4/6 inhibition in GBM.

  Proceedings of the National Academy of Sciences of the United States of America 20100622

• Proliferative suppression by CDK4/6 inhibition: complex function of the retinoblastoma pathway in liver tissue and hepatoma cells.

  Gastroenterology 20100501

• Pharmacologic inhibition of cyclin-dependent kinases 4 and 6 arrests the growth of glioblastoma multiforme intracranial xenografts.

  Cancer research 20100415

• The landscape of somatic copy-number alteration across human cancers.

  Nature 20100218

• Radiosynthesis and radiopharmacological evaluation of cyclin-dependent kinase 4 (Cdk4) inhibitors.

  European journal of medicinal chemistry 20100201

• Epigenetic silencing of the tumor suppressor microRNA Hsa-miR-124a regulates CDK6 expression and confers a poor prognosis in acute lymphoblastic leukemia.

  Cancer research 20090515

• Stem cell factor and interleukin-2/15 combine to enhance MAPK-mediated proliferation of human natural killer cells.

  Blood 20090319

• Treatment of growing teratoma syndrome.

  The New England journal of medicine 20090122

• Advancing bioluminescence imaging technology for the evaluation of anticancer agents in the MDA-MB-435-HAL-Luc mammary fat pad and subrenal capsule tumor models.

  Clinical cancer research : an official journal of the American Association for Cancer Research 20090101

• 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 : BCR 20090101

• CDK inhibitors as potential breast cancer therapeutics: new evidence for enhanced efficacy in ER+ disease.

  Breast cancer research : BCR 20090101

• A novel therapeutic combination using PD 0332991 and bortezomib: study in the 5T33MM myeloma model.

  Cancer research 20080715

• Pharmacologic inhibition of CDK4/6: mechanistic evidence for selective activity or acquired resistance in acute myeloid leukemia.

  Blood 20070915

• Expression of p16Ink4a compensates for p18Ink4c loss in cyclin-dependent kinase 4/6-dependent tumors and tissues.

  Cancer research 20070515

• Mantle cell lymphoma cells express predominantly cyclin D1a isoform and are highly sensitive to selective inhibition of CDK4 kinase activity.

  Blood 20060901

• A novel orally active small molecule potently induces G1 arrest in primary myeloma cells and prevents tumor growth by specific inhibition of cyclin-dependent kinase 4/6.

  Cancer research 20060801

• Toward understanding the structural basis of cyclin-dependent kinase 6 specific inhibition.

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• Pharmacologic inhibition of cyclin-dependent kinase 4/6 activity arrests proliferation in myoblasts and rhabdomyosarcoma-derived cells.

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  Current opinion in pharmacology 20050801

• Discovery of a potent and selective inhibitor of cyclin-dependent kinase 4/6.

  Journal of medicinal chemistry 20050407

• Specific inhibition of cyclin-dependent kinase 4/6 by PD 0332991 and associated antitumor activity in human tumor xenografts.

  Molecular cancer therapeutics 20041101

• Primary care pediatrics vs. family practice: a nonissue.

  Israel journal of medical sciences 19830801