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oai:recercat.cat:2445/1385582025-12-04T21:42:35Zcom_2072_1057col_2072_478917col_2072_478933

Structure-based design of MptpB inhibitors that reduce multi-drug-resistant mycobacterium tuberculosis survival and infection burden in vivo Vickers, Clare F. Silva, Ana P. G. Chakraborty, Ajanta Fernandez, Paulina Kurepina, Natalia Saville, Charis Naranjo, Yandi Pons Vallès, Miquel Schnettger, Laura S. Gutierrez, Maximiliano G. Park, Steven Keiswirth, Barry N. Perlin, David S. Thomas, Eric J. Cavet, Jennifer S. Tabernero, Lydia Fosforilació Tuberculosi Phosphorylation Tuberculosis Mycobacterium 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 2019-07-30T07:05:23Z 2019-08-28T05:10:20Z 2018-08-28 2019-07-30T07:05:24Z info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion 0022-2623 https://hdl.handle.net/2445/138558 682384 30153005 eng Versió postprint del document publicat a: https://doi.org/10.1021/acs.jmedchem.8b00832 Journal of Medicinal Chemistry, 2018, vol. 61, num. 18, p. 8337-8352 https://doi.org/10.1021/acs.jmedchem.8b00832 (c) American Chemical Society , 2018 info:eu-repo/semantics/openAccess 16 p. application/pdf American Chemical Society Articles publicats en revistes (Química Inorgànica i Orgànica)