2022
Synthesis and Structure–Activity relationships of cyclin-dependent kinase 11 inhibitors based on a diaminothiazole scaffold
Li Z, Ishida R, Liu Y, Wang J, Li Y, Gao Y, Jiang J, Che J, Sheltzer JM, Robers MB, Zhang T, Westover KD, Nabet B, Gray NS. Synthesis and Structure–Activity relationships of cyclin-dependent kinase 11 inhibitors based on a diaminothiazole scaffold. European Journal Of Medicinal Chemistry 2022, 238: 114433. PMID: 35597007, PMCID: PMC9477540, DOI: 10.1016/j.ejmech.2022.114433.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisCell Cycle CheckpointsCyclin-Dependent Kinase 2Cyclin-Dependent KinasesStructure-Activity RelationshipConceptsCyclin-dependent kinasesCell cycle regulationG2/M cell cycle arrestM cell cycle arrestCell cycle arrestCellular functionsCycle regulationCellular assaysCycle arrestTool compoundsNeuronal functionAttractive targetCDK11Drug discoveryMedicinal chemistry modificationsStructure-activity relationshipsSplicingTranscriptionInhibitorsMedicinal chemistry campaignKinaseInhibitionApoptosisMRNARegulation
2019
Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials
Lin A, Giuliano CJ, Palladino A, John KM, Abramowicz C, Yuan ML, Sausville EL, Lukow DA, Liu L, Chait AR, Galluzzo ZC, Tucker C, Sheltzer JM. Off-target toxicity is a common mechanism of action of cancer drugs undergoing clinical trials. Science Translational Medicine 2019, 11 PMID: 31511426, PMCID: PMC7717492, DOI: 10.1126/scitranslmed.aaw8412.Peer-Reviewed Original ResearchConceptsClinical trialsCancer drugsDose-limiting toxicityLack of efficacyDrug Administration approvalNumber of therapiesCancer cell proliferationMultiple cancer typesMechanism of actionClinical benefitAdministration approvalCommon causeTrial failuresSmall molecule inhibitorsClinical testingCDK11 expressionHuman patientsPreclinical settingCancer typesU.S. FoodTarget toxicityNew drugsDrugsCell proliferationDrug-indication pairs