Contribution of direct InhA inhibitors to novel drug regimens in a mouse model of tuberculosis

Encinas, Lourdes (avtor), Li, Si-Yang (avtor), Rullas-Trincado, Joaquin (avtor), Tasneen, Rokeya (avtor), Tyagi, Sandeep (avtor), Soni, Heena (avtor), Garcia-Perez, Adolfo (avtor), Lee, Jin (avtor), Sosič, Izidor (avtor), Gobec, Stanislav (avtor)

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.

• Jezik: Angleški jezik
• Ključne besede: InhA inhibitor, tuberculosis, mouse, GSK138, GSK3081138A, GSK693, GSK2505693A, tuberculosis drugs
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.01 - Izvirni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2024
• Št. strani: 17 str.
• Številčenje: Vol. 68, iss. 11
• PID: 20.500.12556/RUL-165224
• UDK: 615.2:616-002.5
• ISSN pri članku: 1098-6596
• DOI: 10.1128/aac.00357-24
• COBISS.SI-ID: 209594883
• Datum objave v RUL: 27.11.2024

Gradivo je del revije

• Naslov: Antimicrobial agents and chemotherapy
• Skrajšan naslov: Antimicrob Agents Chemother
• Založnik: American Society for Microbiology
• ISSN: 1098-6596
• COBISS.SI-ID: 3070228

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: zaviralec InhA, miš, GSK138, GSK3081138A, GSK693, GSK2505693A, zdravila za tuberkulozom tuberkuloza, zdravila

Projekti

• Financer: EC - European Commission
• Program financ.: FP7/2007-2013
• Številka projekta: 261378
• Naslov: Open Collaborative Model for Tuberculosis Lead Optimisation
• Akronim: ORCHID