Structure-based design of MptpB inhibitors that reduce multidrug-resistant Mycobacterium tuberculosis survival and infection burden in vivoMore about Open Access at the Crick
Authors listClare F Vickers Ana PG Silva Ajanta Chakraborty Paulina Fernandez Natalia Kurepina Charis Saville Yandi Naranjo Miquel Pons Laura S Schnettger Maximiliano Gutierrez Steven Park Barry N Kreiswith David S Perlin Eric J Thomas Jennifer S Cavet Lydia Tabernero
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.
Journal Journal of Medicinal Chemistry
Issue number 18