2023
Protein degraders enter the clinic — a new approach to cancer therapy
Chirnomas D, Hornberger K, Crews C. Protein degraders enter the clinic — a new approach to cancer therapy. Nature Reviews Clinical Oncology 2023, 20: 265-278. PMID: 36781982, DOI: 10.1038/s41571-023-00736-3.Peer-Reviewed Original ResearchConceptsPhase III trialsCancer therapyNovel therapeutic modalitiesIII trialsClinical trialsPreclinical modelsClinical studiesTherapeutic modalitiesPharmacokinetic dataSmall molecule inhibitorsDisease pathogenesisClinical testingTumor typesDrug concentrationsPreclinical researchCancer treatmentPhase IFirst safetyUbiquitin-proteasome systemPatientsProtein degradersTherapyMore evidenceTrialsRigorous evaluation
2007
Life on the edge: Therapeutic uses of cytotoxic natural products
Crews C, Leuenroth S, Okuhara D, Shotwell J, Markowitz G, Yu Z, Somlo S. Life on the edge: Therapeutic uses of cytotoxic natural products. The FASEB Journal 2007, 21: a38-a38. DOI: 10.1096/fasebj.21.5.a38-b.Peer-Reviewed Original ResearchAutosomal dominant polycystic kidney diseaseCytotoxic concentrationsPhase I clinical trialLei Gong TengDominant polycystic kidney diseasePolycystic kidney diseaseKidney diseaseChinese medicinal herbsClinical trialsMurine modelCyst formationClinical potentialTriptolideTherapeutic usesDrug developmentMedicinal herbsCytotoxic activityCalcium channel polycystin-2Cytostatic signalsPolycystin-2Cytotoxic compoundsNatural products
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
1994
GTP-dependent binding of the antiproliferative agent didemnin to elongation factor 1 alpha.
Crews CM, Collins JL, Lane WS, Snapper ML, Schreiber SL. GTP-dependent binding of the antiproliferative agent didemnin to elongation factor 1 alpha. Journal Of Biological Chemistry 1994, 269: 15411-15414. PMID: 8195179, DOI: 10.1016/s0021-9258(17)40692-2.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAnti-Infective AgentsCarrier ProteinsCattleChromatography, AffinityDepsipeptidesGuanosine TriphosphateHumansIndicators and ReagentsKineticsMolecular Sequence DataPeptide Elongation Factor 1Peptide Elongation FactorsPeptides, CyclicProtein Synthesis InhibitorsSequence Homology, Amino AcidConceptsEF-1 alphaPotential antineoplastic drugElongation factor 1 alphaDidemnin BProtein synthesisAntiproliferative activityG1 cell cycle progressionGTP-dependent bindingFactor 1 alphaClinical trialsCell cycle progressionImmunosuppressive activityAntineoplastic drugsPeptide sequence analysisElongation factorMode of actionUndefined mechanismPresence of GTPGTPase activityCycle progressionNanomolar concentrationsSequence analysisAlphaMarine natural productsIntracellular targets