Please use this identifier to cite or link to this item: http://hdl.handle.net/2445/138558
Title: Structure-based design of MptpB inhibitors that reduce multi-drug-resistant mycobacterium tuberculosis survival and infection burden in vivo
Author: 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
Keywords: Fosforilació
Tuberculosi
Phosphorylation
Tuberculosis
Issue Date: 28-Aug-2018
Publisher: American Chemical Society
Abstract: 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
Note: Versió postprint del document publicat a: https://doi.org/10.1021/acs.jmedchem.8b00832
It is part of: Journal of Medicinal Chemistry, 2018, vol. 61, num. 18, p. 8337-8352
URI: http://hdl.handle.net/2445/138558
Related resource: https://doi.org/10.1021/acs.jmedchem.8b00832
ISSN: 0022-2623
Appears in Collections:Articles publicats en revistes (Química Inorgànica i Orgànica)

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