20.500.12556/RUL-165224 Contribution of direct InhA inhibitors to novel drug regimens in a mouse model of tuberculosis Isoniazid is an important first-line medicine to treat tuberculosis (TB). Isoniazid resistance increases the risk of poor treatment outcomes and development of multidrug resistance, and is driven primarily by mutations involving katG, encoding the prodrug-activating enzyme, rather than its validated target, InhA. The chemical tractability of InhA has fostered efforts to discover direct inhibitors of InhA (DIIs). In this study, we bridge the gap in understanding the potential contribution of DIIs to novel combination regimens and demonstrate a clear distinction of DIIs, like GSK693 and the newly described GSK138, from isoniazid, based on activity against clinical isolates and contribution to novel drug regimens. The results suggest that DIIs, specifically GSK138 and GSK693, could be promising partners in novel drug regimens, including those used against isoniazid-resistant TB, potentially enhancing their efficacy and/or preventing the selection of resistant mutants and supporting the continued exploration of InhA as a promising target for TB drug development. InhA inhibitor tuberculosis mouse GSK138 GSK3081138A GSK693 GSK2505693A tuberculosis drugs zaviralec InhA miš GSK138 GSK3081138A GSK693 GSK2505693A zdravila za tuberkulozom tuberkuloza zdravila true false true Angleški jezik Slovenski jezik Članek v reviji 2024-11-27 10:52:24 2024-11-27 10:52:28 2024-11-28 04:02:42 0000-00-00 00:00:00 2024 0 0 17 str. iss. 11 Vol. 68 2024 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 615.2:616-002.5 1098-6596 10.1128/aac.00357-24 209594883 encinas-et-al-2024-contribution-of-direct-inha-inhibitors-to-novel-drug-regimens-in-a-mouse-model-of-tuberculosis_(1).pdf encinas-et-al-2024-contribution-of-direct-inha-inhibitors-to-novel-drug-regimens-in-a-mouse-model-of-tuberculosis_(1).pdf 1 CD6B627A292DAC07629E5C139C24A5B9 4a65a18e951d376ecc93e0c0b0a3a5ae93321265bba42d7e51e38091fe18ff6d 8dab582d-aca5-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=196270 https://journals.asm.org/doi/epub/10.1128/aac.00357-24 1 e6ecc892-aca4-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=196269 https://journals.asm.org/doi/10.1128/aac.00357-24 1 e6c698b8-aca4-11ef-b232-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=196268 Fakulteta za farmacijo 0 0 0