Synonyms: GSK286
Compound class:
Synthetic organic
Comment: GSK2556286 is a substituted 4-aryloxypiperidine identified from a screen of compounds that inhibit intracellular growth of Mycobacterium tuberculosis in human macrophage-like differentiated monocytes (THP-1 cell line) [2]. It has a novel cholesterol-dependent mechanism of action, with recent studies establishing it as an agonist of mycobacterial Rv1625c, a membrane-bound adenylyl cyclase [1-2]. GSK2556286 is under clinical development as a potential treatment for tuberculosis (TB).
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Bioactivity Comments |
In vitro, GSK2556286 demonstrates potent inhibition of M. tuberculosis H37Rv growth within human THP-1 cells (IC50 = 0.07 μM) but requires medium containing cholesterol for extracellular activity against H37Rv [2]. In addition, GSK2556286 demonstrates activity (when cultured in cholesterol-containing medium) against multidrug-resistant (MDR) and extensively drug-resistant (XDR) M. tuberculosis clinical isolates and against Mycobacterium africanum and Mycobacterium bovis (MIC90 range, 0.3-1.4 μM) [2]. |