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DC Field | Value | Language |
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dc.contributor.author | Cox, Jonathan A G | - |
dc.contributor.author | Mugumbate, Grace | - |
dc.contributor.author | Peral, Laura Vela-Glez Del | - |
dc.contributor.author | Jankute, Monika | - |
dc.contributor.author | Abrahams, Katherine A | - |
dc.contributor.author | Jervis, Peter | - |
dc.contributor.author | Jackenkroll, Stefan | - |
dc.contributor.author | Perez, Arancha | - |
dc.contributor.author | Alemparte, Carlos | - |
dc.contributor.author | Esquivias, Jorge | - |
dc.contributor.author | Lelièvre, Joël | - |
dc.contributor.author | Ramon, Fernando | - |
dc.contributor.author | Barros, David | - |
dc.contributor.author | Ballell, Lluis | - |
dc.contributor.author | Besra, Gurdyal S | - |
dc.date.accessioned | 2022-06-28T09:51:03Z | - |
dc.date.available | 2022-06-28T09:51:03Z | - |
dc.date.issued | 2016 | - |
dc.identifier.issn | 2045-2322 | - |
dc.identifier.other | DOI: 10.1038/srep38986 | - |
dc.identifier.uri | https://www.nature.com/articles/srep38986 | - |
dc.identifier.uri | http://hdl.handle.net/11408/4905 | - |
dc.description.abstract | High-throughput phenotypic screens have re-emerged as screening tools in antibiotic discovery. The advent of such technologies has rapidly accelerated the identification of 'hit' compounds. A pre-requisite to medicinal chemistry optimisation programmes required to improve the drug-like properties of a 'hit' molecule is identification of its mode of action. Herein, we have combined phenotypic screening with a biased target-specific screen. The inosine monophosphate dehydrogenase (IMPDH) protein GuaB2 has been identified as a drugable target in Mycobacterium tuberculosis, however previously identified compounds lack the desired characteristics necessary for further development into lead-like molecules. This study has identified 7 new chemical series from a high-throughput resistance-based phenotypic screen using Mycobacterium bovis BCG over-expressing GuaB2. Hit compounds were identified in a single shot high-throughput screen, validated by dose response and subjected to further biochemical analysis. The compounds were also assessed using molecular docking experiments, providing a platform for their further optimisation using medicinal chemistry. This work demonstrates the versatility and potential of GuaB2 as an anti-tubercular drug target. | en_US |
dc.language.iso | en | en_US |
dc.publisher | Nature Research | en_US |
dc.relation.ispartofseries | Scientific reports;Vol. 6,No. 38986 | - |
dc.subject | Antibiotics | en_US |
dc.subject | High-throughput screening | en_US |
dc.subject | Phenotypic screening | en_US |
dc.subject | Target validation | en_US |
dc.title | Novel inhibitors of Mycobacterium tuberculosis GuaB2 identified by a target based high-throughput phenotypic screen | en_US |
dc.type | Article | en_US |
item.fulltext | With Fulltext | - |
item.cerifentitytype | Publications | - |
item.languageiso639-1 | en | - |
item.grantfulltext | open | - |
item.openairecristype | http://purl.org/coar/resource_type/c_18cf | - |
item.openairetype | Article | - |
Appears in Collections: | Research Papers |
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File | Description | Size | Format | |
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Novel inhibitors. pdf.pdf | Full Text.pdf | 3.36 MB | Adobe PDF | View/Open |
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