2023. Brown KL, Wilburn KM, Montague CR, Grigg JC, Sanz O, Pérez-Herrán E, Barros D, Ballell L, VanderVen BC, Eltis LD.
Cyclic AMP-Mediated Inhibition of Cholesterol Catabolism in Mycobacterium tuberculosis by the Novel Drug Candidate GSK2556286. Antimicrob Agents Chemother. 2023 Jan 24;67(1):e0129422. doi: 10.1128/aac.01294-22. Epub 2023 Jan 5. PMID: 36602336; PMCID: PMC9872607.
https://pubmed.ncbi.nlm.nih.gov/36602336/
Spontaneous mutants that were resistant to GSK286 were also resistant to mCLB073 and vice versa
2022. Nuermberger EL, Martínez-Martínez MS, Sanz O, Urones B, Esquivias J, Soni H, Tasneen R, Tyagi S, Li SY, Converse PJ, Boshoff HI, Robertson GT, Besra GS, Abrahams KA, Upton AM, Mdluli K, Boyle GW, Turner S, Fotouhi N, Cammack NC, Siles JM, Alonso M, Escribano J, Lelievre J, Rullas-Trincado J, Pérez-Herrán E, Bates RH, Maher-Edwards G, Barros D, Ballell L, Jiménez E.
GSK2556286 Is a Novel Antitubercular Drug Candidate Effective In Vivo with the Potential To Shorten Tuberculosis Treatment. Antimicrob Agents Chemother. 2022 Jun 21;66(6):e0013222. doi: 10.1128/aac.00132-22. Epub 2022 May 24. PMID: 35607978; PMCID: PMC9211396.
GSK 2556286 began Phase 1 clinical study in November 2020. Expected completion June 30, 2023.
GSK 2556286 (GSK-286) is a new chemical entity with a novel mechanism of action related to cholesterol catabolism. GSK-286 selectively kills intracellular Mtb: MIC H37Rv > 10 uM, intramacrophage activity is < 0.1 uM. It penetrates into necrotic lesions (MALDI) and reduces inflammation (PET/CT of infected marmosets). It has been shown to be active in vivo across species (mice, rabbits, monkeys) and reduces relapse rates in mice. It was selected as a clinical candidate in July 2017. First in human study begun 4th quarter 2020.