Structure-Based Design of MptpB Inhibitors That Reduce Multidrug-Resistant Mycobacterium tuberculosis Survival and Infection Burden in Vivo | Zendy

Clare Vickers | Zendy; Ana P. G. Silva | Zendy; Ajanta Chakraborty | Zendy; Paulina Fernández | Zendy; Natalia Kurepina | Zendy; Charis R. Saville | Zendy; Yandi Naranjo | Zendy; Miquel Pons | Zendy; Laura Schnettger | Zendy; Maximiliano G. Gutiérrez | Zendy; Steven Park | Zendy; Barry N. Kreiswith | Zendy; David S. Perlin | Zendy; Eric J. Thomas | Zendy; Jim Cavet | Zendy; Lydia Tabernero | Zendy

Open Access

Structure-Based Design of MptpB Inhibitors That Reduce Multidrug-Resistant Mycobacterium tuberculosis Survival and Infection Burden in Vivo

Author(s) -

Clare Vickers,

Ana P. G. Silva,

Ajanta Chakraborty,

Paulina Fernández,

Natalia Kurepina,

Charis R. Saville,

Yandi Naranjo,

Miquel Pons,

Laura Schnettger,

Maximiliano G. Gutiérrez,

Steven Park,

Barry N. Kreiswith,

David S. Perlin,

Eric J. Thomas,

Jim Cavet,

Lydia Tabernero

Publication year - 2018

Publication title -

journal of medicinal chemistry

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 2.01

H-Index - 261

eISSN - 1520-4804

pISSN - 0022-2623

DOI - 10.1021/acs.jmedchem.8b00832

Subject(s) - mycobacterium tuberculosis , tuberculosis , microbiology and biotechnology , antibiotics , in vivo , virulence , virulence factor , antimicrobial , protein tyrosine phosphatase , multiple drug resistance , chemistry , immunology , pharmacology , medicine , biology , enzyme , biochemistry , pathology , gene

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.

The content you want is available to Zendy users.

Already have an account? Click here to sign in.

Having issues? You can contact us here

Accelerating Research