A Preclinical Candidate Targeting Mycobacterium tuberculosis KasA.

Clicks: 276
ID: 100929
2020
Article Quality & Performance Metrics
Overall Quality Improving Quality
0.0 /100
Combines engagement data with AI-assessed academic quality
AI Quality Assessment
Not analyzed
Abstract
Published Mycobacterium tuberculosis β-ketoacyl-ACP synthase KasA inhibitors lack sufficient potency and/or pharmacokinetic properties. A structure-based approach was used to optimize existing KasA inhibitor DG167. This afforded indazole JSF-3285 with a 30-fold increase in mouse plasma exposure. Biochemical, genetic, and X-ray studies confirmed JSF-3285 targets KasA. JSF-3285 offers substantial activity in an acute mouse model of infection and in the corresponding chronic infection model, with efficacious reductions in colony-forming units at doses as low as 5 mg/kg once daily orally and improvement of the efficacy of front-line drugs isoniazid or rifampicin. JSF-3285 is a promising preclinical candidate for tuberculosis.
Reference Key
inoyama2020acell Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Inoyama, Daigo;Awasthi, Divya;Capodagli, Glenn C;Tsotetsi, Kholiswa;Sukheja, Paridhi;Zimmerman, Matthew;Li, Shao-Gang;Jadhav, Ravindra;Russo, Riccardo;Wang, Xin;Grady, Courtney;Richmann, Todd;Shrestha, Riju;Li, Liping;Ahn, Yong-Mo;Ho Liang, Hsin Pin;Mina, Marizel;Park, Steven;Perlin, David S;Connell, Nancy;Dartois, Véronique;Alland, David;Neiditch, Matthew B;Kumar, Pradeep;Freundlich, Joel S;
Journal cell chemical biology
Year 2020
DOI
S2451-9456(20)30071-4
URL
Keywords
Mycobacterium tuberculosis pharmacokinetics antitubercular jsf-3285 kasa structure-based design

Citations

No citations found. To add a citation, contact the admin at info@scimatic.org

Comments

No comments yet. Be the first to comment on this article.