Efficacy and Improved Resistance Potential of a Cofactor-Independent InhA Inhibitor of Mycobacterium tuberculosis in the C3HeB/FeJ Mouse Model.

Authors :: Robertson GT
Ektnitphong VA
Scherman MS
McNeil MB
Dennison D
Korkegian A
Smith AJ
Halladay J
Carter DS
Xia Y
Zhou Y
Choi W
Berry PW
Mao W
Hernandez V
Alley MRK
Parish T
Lenaerts AJ
Source :: Antimicrobial agents and chemotherapy [Antimicrob Agents Chemother] 2019 Mar 27; Vol. 63 (4). Date of Electronic Publication: 2019 Mar 27 (Print Publication: 2019).
Publication Year :: 2019
Abstract: AN12855 is a direct, cofactor-independent inhibitor of InhA in Mycobacterium tuberculosis In the C3HeB/FeJ mouse model with caseous necrotic lung lesions, AN12855 proved efficacious with a significantly lower resistance frequency than isoniazid. AN12855 drug levels were better retained in necrotic lesions and caseum where the majority of hard to treat, extracellular bacilli reside. Owing to these combined attributes, AN12855 represents a promising alternative to the frontline antituberculosis agent isoniazid.<br /> (Copyright © 2019 Robertson et al.)

Subjects :: Animals
Bacterial Load drug effects
Disease Models, Animal
Drug Development
Female
Isoniazid pharmacology
Lung pathology
Mice
Mice, Inbred C3H
Microbial Sensitivity Tests
Tuberculosis, Pulmonary microbiology
Antitubercular Agents pharmacology
Aza Compounds pharmacology
Boron Compounds pharmacology
Hydrocarbons, Fluorinated pharmacology
Inhibins antagonists & inhibitors
Mycobacterium tuberculosis drug effects
Tuberculosis, Pulmonary drug therapy

Full Text Access

Tools