2011
Drug Repositioning and Pharmacophore Identification in the Discovery of Hookworm MIF Inhibitors
Cho Y, Vermeire JJ, Merkel JS, Leng L, Du X, Bucala R, Cappello M, Lolis E. Drug Repositioning and Pharmacophore Identification in the Discovery of Hookworm MIF Inhibitors. Cell Chemical Biology 2011, 18: 1089-1101. PMID: 21944748, PMCID: PMC3294498, DOI: 10.1016/j.chembiol.2011.07.011.Peer-Reviewed Original ResearchMeSH KeywordsAncylostomatoideaAnimalsAnti-Inflammatory Agents, Non-SteroidalBinding SitesCatalytic DomainCrystallography, X-RayDiureticsDrug RepositioningFurosemideHigh-Throughput Screening AssaysHookworm InfectionsHumansKineticsMacrophage Migration-Inhibitory FactorsMeclofenamic AcidSmall Molecule LibrariesConceptsNonsteroidal anti-inflammatory drugsMacrophage migration inhibitory factorMigration inhibitory factorAnti-inflammatory drugsIntestinal nematode parasitesSodium meclofenamateHigh-throughput screenMIF inhibitorsAnimal modelsTherapeutic efficacyBioactive compound librariesInhibitory factorHookworm diseaseDiuretic activityPartial protectionTautomerase activityFurosemideDiseaseDrugsFDADrug repositioningSubmicromolar inhibitionInhibitorsNew pharmacophoreDiuretics
2010
AV411 (Ibudilast) and AV1013 are non-competitive inhibitors of macrophage migration inhibitory factor: a novel induced-fit allosteric inhibition mechanism (133.11)
Cho Y, Crichlow G, Vermeire J, Leng L, Du X, Hodsdon M, Bucala R, Cappello M, Gross M, Gaeta F, Johnson K, Lolis E. AV411 (Ibudilast) and AV1013 are non-competitive inhibitors of macrophage migration inhibitory factor: a novel induced-fit allosteric inhibition mechanism (133.11). The Journal Of Immunology 2010, 184: 133.11-133.11. DOI: 10.4049/jimmunol.184.supp.133.11.Peer-Reviewed Original ResearchMacrophage migration inhibitory factorMigration inhibitory factorInhibitory factorPro-inflammatory proteinsAnti-inflammatory activityAnti-inflammatory drugsNon-selective inhibitorPDE inhibitor rolipramNeuropathic painOpioid withdrawalBronchial asthmaOcular indicationsGlial cellsNon-competitive inhibitorPossible therapeuticsInhibitor rolipramChemotactic functionAV411Tautomerase activityInhibitorsAllosteric binding siteIsobutylmethylxanthineTreatmentAsthmaPain
2005
Discovery and pre-clinical development of antithrombotics from hematophagous invertebrates.
Ledizet M, Harrison LM, Koskia RA, Cappello M. Discovery and pre-clinical development of antithrombotics from hematophagous invertebrates. Cardiovascular & Hematological Agents In Medicinal Chemistry 2005, 3: 1-10. PMID: 15638739, DOI: 10.2174/1568016052773315.Peer-Reviewed Reviews, Practice Guidelines, Standards, and Consensus StatementsConceptsNumerous invertebrate speciesHematophagous invertebratesInvertebrate speciesSpecific inhibitorUnique specificityInvertebratesFunctional strategiesCritical roleImpressive arrayActivation of thrombosisUseful therapeutic agentPre-clinical developmentNatural productsInhibitorsPlatelet inhibitorsHeart diseaseHuman illnessPlatelet functionClinical developmentSpeciesTherapeutic agentsAntithromboticsParasitesBloodmealThrombosis
2004
Molecular Characterization of Ancylostoma ceylanicum Kunitz-Type Serine Protease Inhibitor: Evidence for a Role in Hookworm-Associated Growth Delay
Chu D, Bungiro RD, Ibanez M, Harrison LM, Campodonico E, Jones BF, Mieszczanek J, Kuzmic P, Cappello M. Molecular Characterization of Ancylostoma ceylanicum Kunitz-Type Serine Protease Inhibitor: Evidence for a Role in Hookworm-Associated Growth Delay. Infection And Immunity 2004, 72: 2214-2221. PMID: 15039345, PMCID: PMC375216, DOI: 10.1128/iai.72.4.2214-2221.2004.Peer-Reviewed Original ResearchConceptsGrowth delayAdult hookwormsIron deficiency anemiaPolyclonal immunoglobulin GDeficiency anemiaHookworm infectionReverse transcription-PCRKunitz-type serine protease inhibitorImmunohistochemistry studiesBroad-spectrum inhibitorPartial protectionMajor causeImmunoglobulin GSerine protease inhibitorIntestinal proteasesThird-stage larvaeTranscription-PCRProtease inhibitorsAnemiaHookwormVivo roleMalnutritionInhibitorsInfected hostPancreatic elastase
1999
The Hookworm Platelet Inhibitor: Functional Blockade of Integrins GPIIb/IIIa (αIIbβ3) and GPIa/IIa (α2β1) Inhibits Platelet Aggregation and Adhesion In Vitro
Chadderdon R, Cappello M. The Hookworm Platelet Inhibitor: Functional Blockade of Integrins GPIIb/IIIa (αIIbβ3) and GPIa/IIa (α2β1) Inhibits Platelet Aggregation and Adhesion In Vitro. The Journal Of Infectious Diseases 1999, 179: 1235-1241. PMID: 10191228, DOI: 10.1086/314724.Peer-Reviewed Original ResearchConceptsIntegrin GPIIb/IIIaPlatelet inhibitorsSoluble protein extractsGPIIb/IIIaPlatelet aggregationMolecular massProtein extractsIron deficiency anemiaGPIa/IIaInhibitory monoclonal antibodiesVariety of agonistsAnti-platelet activityAdult Ancylostoma caninum hookwormsInhibits platelet aggregationPlatelet receptorsDeficiency anemiaFunctional blockadeSpecific blockadeBiologic roleSize exclusion chromatographyIntestinal nematodesSecretory productsMonoclonal antibodiesInhibitorsAdult worms
1996
Anticoagulant repertoire of the hookworm Ancylostoma caninum.
Stassens P, Bergum P, Gansemans Y, Jespers L, Laroche Y, Huang S, Maki S, Messens J, Lauwereys M, Cappello M, Hotez P, Lasters I, Vlasuk G. Anticoagulant repertoire of the hookworm Ancylostoma caninum. Proceedings Of The National Academy Of Sciences Of The United States Of America 1996, 93: 2149-2154. PMID: 8700900, PMCID: PMC39925, DOI: 10.1073/pnas.93.5.2149.Peer-Reviewed Original ResearchConceptsHookworm Ancylostoma caninumReactive site residuesFVIIa/TFBlood coagulation factor VIIaBlood coagulation factor XaMolecular cloningSerine protease inhibitorMammalian hostsCysteine residuesHost hemostasisSite residuesCoagulation factor VIIaHomologous regionsSequence positionsAncylostoma caninumNematode AscarisCatalytic centerBinary complexUnique mechanismCoagulation factor XaProtease inhibitorsResiduesInhibitorsTissue factorThird form
1995
Ancylostoma caninum anticoagulant peptide: a hookworm-derived inhibitor of human coagulation factor Xa.
Cappello M, Vlasuk G, Bergum P, Huang S, Hotez P. Ancylostoma caninum anticoagulant peptide: a hookworm-derived inhibitor of human coagulation factor Xa. Proceedings Of The National Academy Of Sciences Of The United States Of America 1995, 92: 6152-6156. PMID: 7597095, PMCID: PMC41660, DOI: 10.1073/pnas.92.13.6152.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAncylostomaAnimalsArthropod ProteinsBlood CoagulationChromatography, GelChromatography, High Pressure LiquidChromatography, Ion ExchangeFactor Xa InhibitorsHelminth ProteinsHirudinsHumansIntercellular Signaling Peptides and ProteinsKineticsMass SpectrometryMolecular Sequence DataPeptide FragmentsPeptidesProthrombin TimeRecombinant ProteinsSerine Proteinase InhibitorsTicksConceptsBlood lossFactor XaIntestinal blood lossGastrointestinal blood lossHuman hookworm infectionIron deficiency anemiaSoil-transmitted helminthsHuman coagulation factor XaFree factor XaAnticoagulant peptideSpecific inhibitorHookworm infectionDeficiency anemiaProthrombin timeIntestinal mucosaCoagulation factor XaMajor causeRecombinant hirudinChromogenic assayMajor anticoagulantAdult wormsAnticoagulantsProtease inhibitorsHuman coagulationInhibitors