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
1999
Towards subunit-specific proteasome inhibitors: synthesis and evaluation of peptide α', β'-epoxyketones
Elofsson M, Splittgerber U, Myung J, Mohan R, Crews C. Towards subunit-specific proteasome inhibitors: synthesis and evaluation of peptide α', β'-epoxyketones. Cell Chemical Biology 1999, 6: 811-822. PMID: 10574782, DOI: 10.1016/s1074-5521(99)80128-8.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsAortaCattleCell DivisionCells, CulturedChymotrypsinCysteine EndopeptidasesCysteine Proteinase InhibitorsDrug DesignEndothelium, VascularEpoxy CompoundsGlutamatesIndicators and ReagentsIrritantsKineticsMacromolecular SubstancesMiceMolecular ConformationMultienzyme ComplexesPeptidesProteasome Endopeptidase ComplexTrypsinConceptsCatalytic activityMolecular probesAcetylated peptidesExcellent selectivityPotent proteasome inhibitorVivo anti-inflammatory activityMost compoundsMajor catalytic activityChymotrypsin-like activityPeptide αAromatic amino acidsEpoxyketonesAminoP2-P4Multicatalytic protease complexPeptidesAnti-inflammatory activitySelectivityProbeLarge multicatalytic protease complexesProteasome inhibitorsAmino acidsSynthesisCompoundsComplexesTotal synthesis of the-potent proteasome inhibitor epoxomicin: a useful tool for understanding proteasome biology
Sin N, Kim K, Elofsson M, Meng L, Auth H, Kwok B, Crews C. Total synthesis of the-potent proteasome inhibitor epoxomicin: a useful tool for understanding proteasome biology. Bioorganic & Medicinal Chemistry Letters 1999, 9: 2283-2288. PMID: 10465562, DOI: 10.1016/s0960-894x(99)00376-5.Peer-Reviewed Original ResearchConceptsAnti-inflammatory activityProteasome inhibitor epoxomicinSpecific cellular targetsCellular targetsEpoxomicinProteasome biology