{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:10:26Z","timestamp":1791159026525,"version":"4.1.0"},"reference-count":33,"publisher":"American Society for Microbiology","issue":"3","license":[{"start":{"date-parts":[[2015,3,1]],"date-time":"2015-03-01T00:00:00Z","timestamp":1425168000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2015,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    New drugs to treat drug-resistant tuberculosis are urgently needed. Extensively drug-resistant and probably the totally drug-resistant tuberculosis strains are resistant to fluoroquinolones like moxifloxacin, which target gyrase A, and most people infected with these strains die within a year. In this study, we found that a novel aminobenzimidazole, VXc-486, which targets gyrase B, potently inhibits multiple drug-sensitive isolates and drug-resistant isolates of\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Mycobacterium tuberculosis<\/jats:named-content>\n                    <jats:italic>in vitro<\/jats:italic>\n                    (MICs of 0.03 to 0.30 \u03bcg\/ml and 0.08 to 5.48 \u03bcg\/ml, respectively) and reduces mycobacterial burdens in lungs of infected mice\n                    <jats:italic>in vivo<\/jats:italic>\n                    . VXc-486 is active against drug-resistant isolates, has bactericidal activity, and kills intracellular and dormant\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">M. tuberculosis<\/jats:named-content>\n                    bacteria in a low-oxygen environment. Furthermore, we found that VXc-486 inhibits the growth of multiple strains of\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Mycobacterium abscessus<\/jats:named-content>\n                    ,\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Mycobacterium avium<\/jats:named-content>\n                    complex, and\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Mycobacterium kansasii<\/jats:named-content>\n                    (MICs of 0.1 to 2.0 \u03bcg\/ml), as well as that of several strains of\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Nocardia<\/jats:named-content>\n                    spp. (MICs of 0.1 to 1.0 \u03bcg\/ml). We made a direct comparison of the parent compound VXc-486 and a phosphate prodrug of VXc-486 and showed that the prodrug of VXc-486 had more potent killing of\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">M. tuberculosis<\/jats:named-content>\n                    than did VXc-486\n                    <jats:italic>in vivo<\/jats:italic>\n                    . In combination with other antimycobacterial drugs, the prodrug of VXc-486 sterilized\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">M. tuberculosis<\/jats:named-content>\n                    infection when combined with rifapentine-pyrazinamide and bedaquiline-pyrazinamide in a relapse infection study in mice. Furthermore, the prodrug of VXc-486 appeared to perform at least as well as the gyrase A inhibitor moxifloxacin. These findings warrant further development of the prodrug of VXc-486 for the treatment of tuberculosis and nontuberculosis mycobacterial infections.\n                  <\/jats:p>","DOI":"10.1128\/aac.04347-14","type":"journal-article","created":{"date-parts":[[2014,12,22]],"date-time":"2014-12-22T22:11:33Z","timestamp":1419286293000},"page":"1455-1465","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":80,"title":["A Novel Inhibitor of Gyrase B Is a Potent Drug Candidate for Treatment of Tuberculosis and Nontuberculosis Mycobacterial Infections"],"prefix":"10.1128","volume":"59","author":[{"given":"Christopher P.","family":"Locher","sequence":"first","affiliation":[{"name":"Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven M.","family":"Jones","sequence":"additional","affiliation":[{"name":"Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian L.","family":"Hanzelka","sequence":"additional","affiliation":[{"name":"Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuele","family":"Perola","sequence":"additional","affiliation":[{"name":"Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn M.","family":"Shoen","sequence":"additional","affiliation":[{"name":"Central New York Research Corporation, Syracuse, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael H.","family":"Cynamon","sequence":"additional","affiliation":[{"name":"Central New York Research Corporation, Syracuse, New York, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andile H.","family":"Ngwane","sequence":"additional","affiliation":[{"name":"DST\/NRF Centre of Excellence for Biomedical Tuberculosis Research\/MRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ian J.","family":"Wiid","sequence":"additional","affiliation":[{"name":"DST\/NRF Centre of Excellence for Biomedical Tuberculosis Research\/MRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul D.","family":"van Helden","sequence":"additional","affiliation":[{"name":"DST\/NRF Centre of Excellence for Biomedical Tuberculosis Research\/MRC Centre for Tuberculosis Research, Division of Molecular Biology and Human Genetics, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrice","family":"Betoudji","sequence":"additional","affiliation":[{"name":"Center for Tuberculosis Research, Johns Hopkins School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric L.","family":"Nuermberger","sequence":"additional","affiliation":[{"name":"Center for Tuberculosis Research, Johns Hopkins School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John A.","family":"Thomson","sequence":"additional","affiliation":[{"name":"Vertex Pharmaceuticals Incorporated, Boston, Massachusetts, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","volume-title":"Global tuberculosis report 2014","author":"World Health Organization","year":"2014","unstructured":"World Health Organization. 2014. 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