{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Brown KL"],"funding":["Canadian Lung Association","NIAID NIH HHS","HHS | NIH | National Institute of Allergy and Infectious Diseases","Gouvernement du Canada | Canadian Institutes of Health Research"],"pagination":["e0129422"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9872607"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["67(1)"],"pubmed_abstract":["Despite the deployment of combination tuberculosis (TB) chemotherapy, efforts to identify shorter, nonrelapsing treatments have resulted in limited success. Recent evidence indicates that GSK2556286 (GSK286), which acts via Rv1625c, a membrane-bound adenylyl cyclase in Mycobacterium tuberculosis, shortens treatment in rodents relative to standard of care drugs. Moreover, GSK286 can replace linezolid in the three-drug, Nix-TB regimen. Given its therapeutic potential, we sought to better understand the mechanism of action of GSK286. The compound blocked growth of <i>M. tuberculosis</i> in cholesterol media and increased intracellular cAMP levels ~50-fold. GSK286 did not inhibit growth of an <i>rv1625c</i> transposon mutant in cholesterol media and did not induce cyclic AMP (cAMP) production "],"journal":["Antimicrobial agents and chemotherapy"],"pubmed_title":["Cyclic AMP-Mediated Inhibition of Cholesterol Catabolism in <i>Mycobacterium tuberculosis</i> by the Novel Drug Candidate GSK2556286."],"pmcid":["PMC9872607"],"funding_grant_id":["R01 AI130018","AI130018","PJT-159574","AI119122","R01 AI119122"],"pubmed_authors":["Wilburn KM","Montague CR","Eltis LD","Sanz O","Brown KL","Ballell L","Grigg JC","Barros D","Perez-Herran E","VanderVen BC"],"additional_accession":[]},"is_claimable":false,"name":"Cyclic AMP-Mediated Inhibition of Cholesterol Catabolism in <i>Mycobacterium tuberculosis</i> by the Novel Drug Candidate GSK2556286.","description":"Despite the deployment of combination tuberculosis (TB) chemotherapy, efforts to identify shorter, nonrelapsing treatments have resulted in limited success. Recent evidence indicates that GSK2556286 (GSK286), which acts via Rv1625c, a membrane-bound adenylyl cyclase in Mycobacterium tuberculosis, shortens treatment in rodents relative to standard of care drugs. Moreover, GSK286 can replace linezolid in the three-drug, Nix-TB regimen. Given its therapeutic potential, we sought to better understand the mechanism of action of GSK286. The compound blocked growth of <i>M. tuberculosis</i> in cholesterol media and increased intracellular cAMP levels ~50-fold. GSK286 did not inhibit growth of an <i>rv1625c</i> transposon mutant in cholesterol media and did not induce cyclic AMP (cAMP) production ","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Jan","modification":"2026-06-08T06:39:43.539Z","creation":"2025-04-07T10:25:16.512Z"},"accession":"S-EPMC9872607","cross_references":{"pubmed":["36602336"],"doi":["10.1128/aac.01294-22"]}}