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

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...

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Autores principales: Robertson, Gregory T., Ektnitphong, Victoria A., Scherman, Michael S., McNeil, Matthew B., Dennison, Devon, Korkegian, Aaron, Smith, Anthony J., Halladay, Jason, Carter, David S., Xia, Yi, Zhou, Yasheen, Choi, Wai, Berry, Pamela W., Mao, Weimin, Hernandez, Vincent, Alley, M. R. K., Parish, Tanya, Lenaerts, Anne J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Microbiology 2019
Materias:
Experimental Therapeutics
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6496157/
https://www.ncbi.nlm.nih.gov/pubmed/30745397
http://dx.doi.org/10.1128/AAC.02071-18
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author Robertson, Gregory T.
Ektnitphong, Victoria A.
Scherman, Michael S.
McNeil, Matthew B.
Dennison, Devon
Korkegian, Aaron
Smith, Anthony J.
Halladay, Jason
Carter, David S.
Xia, Yi
Zhou, Yasheen
Choi, Wai
Berry, Pamela W.
Mao, Weimin
Hernandez, Vincent
Alley, M. R. K.
Parish, Tanya
Lenaerts, Anne J.
author_facet Robertson, Gregory T.
Ektnitphong, Victoria A.
Scherman, Michael S.
McNeil, Matthew B.
Dennison, Devon
Korkegian, Aaron
Smith, Anthony J.
Halladay, Jason
Carter, David S.
Xia, Yi
Zhou, Yasheen
Choi, Wai
Berry, Pamela W.
Mao, Weimin
Hernandez, Vincent
Alley, M. R. K.
Parish, Tanya
Lenaerts, Anne J.
author_sort Robertson, Gregory T.
collection PubMed
description 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.
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spelling pubmed-64961572019-06-03 Efficacy and Improved Resistance Potential of a Cofactor-Independent InhA Inhibitor of Mycobacterium tuberculosis in the C3HeB/FeJ Mouse Model Robertson, Gregory T. Ektnitphong, Victoria A. Scherman, Michael S. McNeil, Matthew B. Dennison, Devon Korkegian, Aaron Smith, Anthony J. Halladay, Jason Carter, David S. Xia, Yi Zhou, Yasheen Choi, Wai Berry, Pamela W. Mao, Weimin Hernandez, Vincent Alley, M. R. K. Parish, Tanya Lenaerts, Anne J. Antimicrob Agents Chemother Experimental Therapeutics 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. American Society for Microbiology 2019-03-27 /pmc/articles/PMC6496157/ /pubmed/30745397 http://dx.doi.org/10.1128/AAC.02071-18 Text en Copyright © 2019 Robertson et al. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Experimental Therapeutics
Robertson, Gregory T.
Ektnitphong, Victoria A.
Scherman, Michael S.
McNeil, Matthew B.
Dennison, Devon
Korkegian, Aaron
Smith, Anthony J.
Halladay, Jason
Carter, David S.
Xia, Yi
Zhou, Yasheen
Choi, Wai
Berry, Pamela W.
Mao, Weimin
Hernandez, Vincent
Alley, M. R. K.
Parish, Tanya
Lenaerts, Anne J.
Efficacy and Improved Resistance Potential of a Cofactor-Independent InhA Inhibitor of Mycobacterium tuberculosis in the C3HeB/FeJ Mouse Model
title Efficacy and Improved Resistance Potential of a Cofactor-Independent InhA Inhibitor of Mycobacterium tuberculosis in the C3HeB/FeJ Mouse Model
title_full Efficacy and Improved Resistance Potential of a Cofactor-Independent InhA Inhibitor of Mycobacterium tuberculosis in the C3HeB/FeJ Mouse Model
title_fullStr Efficacy and Improved Resistance Potential of a Cofactor-Independent InhA Inhibitor of Mycobacterium tuberculosis in the C3HeB/FeJ Mouse Model
title_full_unstemmed Efficacy and Improved Resistance Potential of a Cofactor-Independent InhA Inhibitor of Mycobacterium tuberculosis in the C3HeB/FeJ Mouse Model
title_short Efficacy and Improved Resistance Potential of a Cofactor-Independent InhA Inhibitor of Mycobacterium tuberculosis in the C3HeB/FeJ Mouse Model
title_sort efficacy and improved resistance potential of a cofactor-independent inha inhibitor of mycobacterium tuberculosis in the c3heb/fej mouse model
topic Experimental Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6496157/
https://www.ncbi.nlm.nih.gov/pubmed/30745397
http://dx.doi.org/10.1128/AAC.02071-18
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