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

Antimicrobial agents and chemotherapy, Volume: 63, Issue: 4
April 27, 2019
Gregory T Robertson GT, Victoria A Ektnitphong VA, Michael S Scherman MS, Matthew B McNeil MB, Devon Dennison D, Aaron Korkegian A, Anthony J Smith AJ, Jason Halladay J, David S Carter DS, Yi Xia Y, Yasheen Zhou Y, Wai Choi W, Pamela W Berry PW, Weimin Mao W, Vincent Hernandez V, M R K Alley MRK, Tanya Parish T, Anne J Lenaerts AJ

AN12855 is a direct, cofactor-independent inhibitor of InhA in 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.

Courtesy of the U.S. National Library of Medicine