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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) |
Files in This Item:
| File | Description | Size | Format | |
|---|---|---|---|---|
| 682384.pdf | 8.82 MB | Adobe PDF | View/Open |
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