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

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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

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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. Structure-based design of MptpB inhibitors that reduce multi-drug-resistant mycobacterium tuberculosis survival and infection burden in vivo. _Journal of Medicinal Chemistry_. 2018. Vol. 61, núm. 18, pàgs. 8337-8352. [consulta: 5 de febrer de 2026]. ISSN: 0022-2623. [Disponible a: https://hdl.handle.net/2445/138558]

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