Structure-based design of MptpB inhibitors that reduce multi-drug-resistant mycobacterium tuberculosis survival and infection burden in vivo

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dc.contributor.authorVickers, Clare F.
dc.contributor.authorSilva, Ana P. G.
dc.contributor.authorChakraborty, Ajanta
dc.contributor.authorFernandez, Paulina
dc.contributor.authorKurepina, Natalia
dc.contributor.authorSaville, Charis
dc.contributor.authorNaranjo, Yandi
dc.contributor.authorPons Vallès, Miquel
dc.contributor.authorSchnettger, Laura S.
dc.contributor.authorGutierrez, Maximiliano G.
dc.contributor.authorPark, Steven
dc.contributor.authorKeiswirth, Barry N.
dc.contributor.authorPerlin, David S.
dc.contributor.authorThomas, Eric J.
dc.contributor.authorCavet, Jennifer S.
dc.contributor.authorTabernero, Lydia
dc.date.accessioned2019-07-30T07:05:23Z
dc.date.available2019-08-28T05:10:20Z
dc.date.issued2018-08-28
dc.date.updated2019-07-30T07:05:24Z
dc.description.abstractMycobacterium tuberculosis protein-tyrosine-phosphatase B (MptpB) is a secreted virulence factor that subverts antimicrobial activity in the host. We report here the structure-based design of selective MptpB inhibitors that reduce survival of multidrug-resistant tuberculosis strains in macrophages and enhance killing efficacy by first-line antibiotics. Monotherapy with an orally bioavailable MptpB inhibitor reduces infection burden in acute and chronic guinea pig models and improves the overall pathology. Our findings provide a new paradigm for tuberculosis treatment
dc.format.extent16 p.
dc.format.mimetypeapplication/pdf
dc.identifier.idgrec682384
dc.identifier.issn0022-2623
dc.identifier.pmid30153005
dc.identifier.urihttps://hdl.handle.net/2445/138558
dc.language.isoeng
dc.publisherAmerican Chemical Society
dc.relation.isformatofVersió postprint del document publicat a: https://doi.org/10.1021/acs.jmedchem.8b00832
dc.relation.ispartofJournal of Medicinal Chemistry, 2018, vol. 61, num. 18, p. 8337-8352
dc.relation.urihttps://doi.org/10.1021/acs.jmedchem.8b00832
dc.rights(c) American Chemical Society , 2018
dc.rights.accessRightsinfo:eu-repo/semantics/openAccess
dc.sourceArticles publicats en revistes (Química Inorgànica i Orgànica)
dc.subject.classificationFosforilació
dc.subject.classificationTuberculosi
dc.subject.otherPhosphorylation
dc.subject.otherTuberculosis
dc.titleStructure-based design of MptpB inhibitors that reduce multi-drug-resistant mycobacterium tuberculosis survival and infection burden in vivo
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:eu-repo/semantics/acceptedVersion

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