2006
Probing Protein Function with Small Molecules
Gough JD, Crews CM. Probing Protein Function with Small Molecules. Ernst Schering Foundation Symposium Proceedings 2006, 58: 61-74. PMID: 16708999, DOI: 10.1007/978-3-540-37635-4_5.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiotinylationCombinatorial Chemistry TechniquesDrug DesignDrug Evaluation, PreclinicalGenomicsGreen Fluorescent ProteinsHumansKetonesModels, ChemicalMolecular Probe TechniquesNanotechnologyOligopeptidesPhosphorylationProtein BindingProteinsReceptors, AndrogenRecombinant Fusion ProteinsSerineSesquiterpenesSignal TransductionUbiquitin-Protein Ligases
2001
The anti-inflammatory natural product parthenolide from the medicinal herb Feverfew directly binds to and inhibits IκB kinase
Kwok B, Koh B, Ndubuisi M, Elofsson M, Crews C. The anti-inflammatory natural product parthenolide from the medicinal herb Feverfew directly binds to and inhibits IκB kinase. Cell Chemical Biology 2001, 8: 759-766. PMID: 11514225, DOI: 10.1016/s1074-5521(01)00049-7.Peer-Reviewed Original ResearchConceptsAnti-inflammatory activityHerb feverfewPro-inflammatory signaling pathwaysDirect molecular targetVivo anti-inflammatory activityAnti-inflammatory propertiesAnti-inflammatory agentsCytokine-mediated stimulationCytokine-mediated signalingIkappaB kinase betaSesquiterpene lactone parthenolidePharmaceutical interventionsIκB kinaseMolecular targetsNatural product parthenolideKinase betaParthenolideCysteine 179Signaling pathwaysPossible molecular basisIntracellular signaling processesAttractive targetIKK complexMolecular mechanismsAlpha-methylene gamma-lactone moiety
2000
The antiangiogenic agent TNP-470 requires p53 and p21CIP/WAF for endothelial cell growth arrest
Yeh J, Mohan R, Crews C. The antiangiogenic agent TNP-470 requires p53 and p21CIP/WAF for endothelial cell growth arrest. Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 12782-12787. PMID: 11070090, PMCID: PMC18841, DOI: 10.1073/pnas.97.23.12782.Peer-Reviewed Original ResearchMeSH KeywordsAdultAngiogenesis InhibitorsAnimalsCell CycleCell DivisionCells, CulturedCorneal NeovascularizationCyclin-Dependent Kinase Inhibitor p21Cyclin-Dependent KinasesCyclinsCyclohexanesEndothelium, VascularGene ExpressionHumansMiceMice, KnockoutNuclear ProteinsO-(Chloroacetylcarbamoyl)fumagillolProto-Oncogene ProteinsProto-Oncogene Proteins c-mdm2SesquiterpenesTumor Suppressor Protein p53ConceptsTNP-470Endothelial cellsAntiangiogenic agent TNP-470Subsequent growth arrestGrowth arrestCyclin-dependent kinase inhibitorAntiangiogenic strategiesPrimary endothelial cellsEndothelial cell growth arrestP21CIP/WAFEndothelial cell cycleCell growth arrestKinase inhibitorsAntiangiogenic activityCell cycle regulatorsAngiogenesis assayCytostatic activityP53 activationMiceCritical cell cycle regulatorsCycle regulatorsUnique mechanismAdult fibroblastsCell-type specificityArrest
1998
Structure of Human Methionine Aminopeptidase-2 Complexed with Fumagillin
Liu S, Widom J, Kemp C, Crews C, Clardy J. Structure of Human Methionine Aminopeptidase-2 Complexed with Fumagillin. Science 1998, 282: 1324-1327. PMID: 9812898, DOI: 10.1126/science.282.5392.1324.Peer-Reviewed Original ResearchConceptsStructure-based drug designMetAP-2Resolution crystal structureCovalent bondsMethionine aminopeptidase 2Active siteCrystal structurePolar interactionsDrug designThree-dimensional structureExtensive hydrophobicStructural basisMetAP-1Anticancer agentsNew blood vesselsFumagillin analoguesAdditional affinityReactive epoxidesMolecular targetsFumagillinStructureHydrophobicBondsLikely determinantsEpoxides
1997
The anti-angiogenic agent fumagillin covalently binds and inhibits the methionine aminopeptidase, MetAP-2
Sin N, Meng L, Wang M, Wen J, Bornmann W, Crews C. The anti-angiogenic agent fumagillin covalently binds and inhibits the methionine aminopeptidase, MetAP-2. Proceedings Of The National Academy Of Sciences Of The United States Of America 1997, 94: 6099-6103. PMID: 9177176, PMCID: PMC21008, DOI: 10.1073/pnas.94.12.6099.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAminopeptidasesAnimalsAntibiotics, AntineoplasticBinding SitesCattleCyclohexanesFatty Acids, UnsaturatedHumansKineticsMammalsMetalloendopeptidasesMethionyl AminopeptidasesMolecular Sequence DataNeovascularization, PathologicO-(Chloroacetylcarbamoyl)fumagillolSaccharomyces cerevisiaeSequence AlignmentSequence Homology, Amino AcidSesquiterpenesConceptsMethionine aminopeptidaseMetAP-1MetAP-2Mammalian proteinsBlood vessel formationVegetative growthTNP-470New blood vessel formationPotent biological activitiesMolecular modeProteinFungal metabolitesVessel formationAnimal model studiesAminopeptidaseAnti-angiogenic compoundsDetailed pharmacological studiesBiological activityImportant targetFumagillinClinical trialsSolid tumorsPharmacological studiesNatural productsSaccharomyces