2024
Regulated induced proximity targeting chimeras—RIPTACs—A heterobifunctional small molecule strategy for cancer selective therapies
Raina K, Forbes C, Stronk R, Rappi J, Eastman K, Zaware N, Yu X, Li H, Bhardwaj A, Gerritz S, Forgione M, Hundt A, King M, Posner Z, Correia A, McGovern A, Puleo D, Chenard R, Mousseau J, Vergara J, Garvin E, Macaluso J, Martin M, Bassoli K, Jones K, Garcia M, Howard K, Yaggi M, Smith L, Chen J, Mayfield A, De Leon C, Hines J, Kayser-Bricker K, Crews C. Regulated induced proximity targeting chimeras—RIPTACs—A heterobifunctional small molecule strategy for cancer selective therapies. Cell Chemical Biology 2024, 31: 1490-1502.e42. PMID: 39116881, PMCID: PMC11371387, DOI: 10.1016/j.chembiol.2024.07.005.Peer-Reviewed Original ResearchProtein-protein interactionsTarget proteinsTernary complexChemical biology studiesExpressed intracellular proteinStable ternary complexAnti-proliferative responseEssential proteinsProtein proximityEffector ligandsIntracellular proteinsCDK inhibitorsTarget-expressing cellsHeterobifunctional small moleculesSmall moleculesCell survivalTumor cellsTherapeutic modalitiesProteinSelective therapySmall molecule strategiesLigandBiological studies
2018
CDK4/6 inhibitors in breast cancer: beyond hormone receptor-positive HER2-negative disease
Matutino A, Amaro C, Verma S. CDK4/6 inhibitors in breast cancer: beyond hormone receptor-positive HER2-negative disease. Therapeutic Advances In Medical Oncology 2018, 10: 1758835918818346. PMID: 30619511, PMCID: PMC6299331, DOI: 10.1177/1758835918818346.Peer-Reviewed Original ResearchTriple-negative breast cancerProgression-free survivalBreast cancerCDK4/6 inhibitorsHormone receptor-positive HER2-negative diseaseCyclin-dependent kinase 4/6 inhibitorsPositive human epidermal growth factor receptor 2Human epidermal growth factor receptor 2Epidermal growth factor receptor 2HER2-negative diseaseGrowth factor receptor 2Metastatic breast cancer therapyNegative breast cancerBreast cancer therapyFactor receptor 2Preclinical evidenceClinical dataReceptor 2Later linesHormone receptorsCancerCancer therapyCell linesInhibitorsCDK inhibitors
2016
Potential Use of Flavopiridol in Treatment of Chronic Diseases
Srikumar T, Padmanabhan J. Potential Use of Flavopiridol in Treatment of Chronic Diseases. Advances In Experimental Medicine And Biology 2016, 929: 209-228. PMID: 27771926, DOI: 10.1007/978-3-319-41342-6_9.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAnti-Inflammatory AgentsAntineoplastic Agents, PhytogenicAntiviral AgentsApoptosisCardiovascular AgentsCell Cycle CheckpointsCell ProliferationChronic DiseaseDisease Models, AnimalDrug DiscoveryFlavonoidsHumansMolecular StructurePhytotherapyPiperidinesPlants, MedicinalSignal TransductionConceptsChronic diseasesElicit anti-inflammatory activityAberrant cell cycle activationNFκB-dependent signalingEffect of flavopiridolAnti-inflammatory activityArrests cell cycle progressionCell cycle activationInflammatory stimuliAnti-apoptotic genesAnti-proliferative activityCell cycle progressionDiseaseInhibits expressionCycle activationFlavopiridolCycle progressionCDK inhibitorsPotential useGrowth-arrested cellsRecent studiesRNA polymerase II activationTreatmentP-TEFb complexActivation
2014
Synergistic tumor suppression by combined inhibition of telomerase and CDKN1A
Gupta R, Dong Y, Solomon PD, Wettersten HI, Cheng CJ, Min JN, Henson J, Dogra SK, Hwang SH, Hammock BD, Zhu LJ, Reddel RR, Saltzman WM, Weiss RH, Chang S, Green MR, Wajapeyee N. Synergistic tumor suppression by combined inhibition of telomerase and CDKN1A. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: e3062-e3071. PMID: 25024194, PMCID: PMC4121806, DOI: 10.1073/pnas.1411370111.Peer-Reviewed Original ResearchConceptsP53-mediated transcriptional activationCyclin-dependent kinase inhibitor 1AMutant p53Telomerase inhibitionTumor suppressor p53Transcriptional activationSynergistic tumor suppressionTelomere dysfunctionCheckpoint proteinsP53 upregulated modulatorTumor suppressionCDK inhibitorsSuppressor p53Inhibitor 1AP53 activityTelomeraseHuman cancersCancer cell linesApoptosis inductionPharmacological inhibitionApoptosisCell linesPharmacological restorationP21Growth inhibition
2006
RB/E2F Regulation and Dual Activity in the Melanocytic System
Halaban R. RB/E2F Regulation and Dual Activity in the Melanocytic System. 2006, 223-245. DOI: 10.1007/978-1-59259-994-3_13.Peer-Reviewed Original ResearchE2F transcriptional activityE2F interactionTranscriptional activityRb/E2F pathwayChromatin modification activitiesCyclin-dependent kinase activityE2F-regulated genesRb-binding proteinCell cycle genesE2F complex formationMelanoma cellsCell cycle progressionCell surface receptorsGene repressionE2F regulationCycle genesE2F pathwayCDK activityApoptosis genesKinase activityB-RafCycle progressionTumor suppressorCDK inhibitorsN-ras
2003
The use of cyclin-dependent kinase inhibitors alone or in combination with established cytotoxic drugs in cancer chemotherapy
Grant S, Roberts JD. The use of cyclin-dependent kinase inhibitors alone or in combination with established cytotoxic drugs in cancer chemotherapy. Drug Resistance Updates 2003, 6: 15-26. PMID: 12654284, DOI: 10.1016/s1368-7646(02)00141-3.Peer-Reviewed Original ResearchConceptsCyclin-dependent kinase inhibitorCytotoxic agentsKinase inhibitorsSingle-agent activityCDK inhibitorsConventional cytotoxic agentsAnti-tumor effectsApoptotic regulatory moleculesCell cycle dysregulationNeoplastic cell proliferationAbundant preclinical evidencePreclinical evidenceTumor cell typesCritical molecular targetsClinical studiesSpecific tumor cell typesPreclinical studiesClinical developmentSmall molecule inhibitorsCell cycle traverseCytotoxic drugsAntitumor efficacyClinical arenaCancer chemotherapyMolecular targets
2001
CAK-independent Activation of CDK6 by a Viral Cyclin
Kaldis P, Ojala P, Tong L, Mäkelä T, Solomon M. CAK-independent Activation of CDK6 by a Viral Cyclin. Molecular Biology Of The Cell 2001, 12: 3987-3999. PMID: 11739795, PMCID: PMC60770, DOI: 10.1091/mbc.12.12.3987.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisCyclin-Dependent Kinase 6Cyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent Kinase-Activating KinaseCyclin-Dependent KinasesCyclinsEnzyme ActivationFluorescent Antibody TechniqueHerpesvirus 8, HumanHumansPhosphorylationProtein ConformationProtein Serine-Threonine KinasesTumor Cells, CulturedViral ProteinsConceptsKSHV-cyclinSarcoma-associated herpesvirusKaposi's sarcoma-associated herpesvirusCell cycle progression independentAbsence of phosphorylationCyclin-dependent kinasesD-type cyclinsCAK phosphorylationExpression of CDK6CDK6 activationMitogenic signalsSubstrate specificityCell-based assaysCDK inhibitorsViral cyclinConformational changesCell deathPhosphorylationCAKCDK inhibitionKinaseCyclinCDK6Ternary complexNormal cells
1998
Human and Yeast Cdk-activating Kinases (CAKs) Display Distinct Substrate Specificities
Kaldis P, Russo A, Chou H, Pavletich N, Solomon M. Human and Yeast Cdk-activating Kinases (CAKs) Display Distinct Substrate Specificities. Molecular Biology Of The Cell 1998, 9: 2545-2560. PMID: 9725911, PMCID: PMC25525, DOI: 10.1091/mbc.9.9.2545.Peer-Reviewed Original ResearchConceptsTranscription factor IIHC-terminal domainSubstrate specificityCDK/cyclin complexesCTD kinase activityRNA polymerase IIDistinct substrate specificitiesDifferent substrate specificitiesCyclin-dependent kinasesCell cycle progressionHuman CAKYeast CdkEnzyme-substrate recognitionPolymerase IILarge subunitTranscriptional componentsCak1pCDK activationCyclin complexesKey residuesKinase activitySingle polypeptideCycle progressionCDK inhibitorsCDK
1994
Inactivation of a Cdk2 inhibitor during interleukin 2-induced proliferation of human T lymphocytes.
Firpo E, Koff A, Solomon M, Roberts J. Inactivation of a Cdk2 inhibitor during interleukin 2-induced proliferation of human T lymphocytes. Molecular And Cellular Biology 1994, 14: 4889-4901. PMID: 7516474, PMCID: PMC358861, DOI: 10.1128/mcb.14.7.4889.Peer-Reviewed Original ResearchMeSH KeywordsAdultCDC2-CDC28 KinasesCell CycleCells, CulturedCyclin-Dependent Kinase 2Cyclin-Dependent Kinase Inhibitor p21Cyclin-Dependent KinasesCyclinsDNAEnzyme ActivationFlow CytometryHumansInterleukin-2KineticsLymphocyte ActivationProtein Kinase InhibitorsProtein KinasesProtein Serine-Threonine KinasesReceptors, Antigen, T-CellReceptors, Interleukin-2Recombinant ProteinsRNASignal TransductionTime FactorsT-LymphocytesConceptsCyclin-dependent kinasesMitogenic signalsCyclin-cdk2 complexesCDK2 inhibitorsNegative growth signalsG1 cyclin-CDK complexesCell cycle commitmentCyclin-CDK complexesCyclin-Cdk inhibitorT cell antigen receptorCell proliferationAntigen receptor stimulationCell cycle proteinsInhibitors of CDK2Mitogenic growth factorsGrowth signalsSimilar proteinsBiochemical pathwaysCell cycleCDK inhibitorsCdk2 activationCycle proteinsRestriction pointS phaseCommon targetInactivation of a Cdk2 Inhibitor during Interleukin 2-Induced Proliferation of Human T Lymphocytes
Firpo E, Koff A, Solomon M, Roberts J. Inactivation of a Cdk2 Inhibitor during Interleukin 2-Induced Proliferation of Human T Lymphocytes. Molecular And Cellular Biology 1994, 14: 4889-4901. DOI: 10.1128/mcb.14.7.4889-4901.1994.Peer-Reviewed Original ResearchCyclin-dependent kinasesMitogenic signalsCyclin-cdk2 complexesCDK2 inhibitorsNegative growth signalsG1 cyclin-CDK complexesCell cycle commitmentCyclin-CDK complexesCyclin-Cdk inhibitorT cell antigen receptorCell proliferationAntigen receptor stimulationCell cycle proteinsInhibitors of CDK2Mitogenic growth factorsGrowth signalsSimilar proteinsBiochemical pathwaysCell cycleCDK inhibitorsCdk2 activationCycle proteinsRestriction pointS phaseCommon target
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