| http://purl.uniprot.org/citations/23798446 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23798446 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/23798446 | http://www.w3.org/2000/01/rdf-schema#comment | "Infection with the bacterial pathogen Mycobacterium tuberculosis imposes an enormous burden on global public health. New antibiotics are urgently needed to combat the global tuberculosis pandemic; however, the development of new small molecules is hindered by a lack of validated drug targets. Here, we describe the identification of a 4,6-diaryl-5,7-dimethyl coumarin series that kills M. tuberculosis by inhibiting fatty acid degradation protein D32 (FadD32), an enzyme that is required for biosynthesis of cell-wall mycolic acids. These substituted coumarin inhibitors directly inhibit the acyl-acyl carrier protein synthetase activity of FadD32. They effectively block bacterial replication both in vitro and in animal models of tuberculosis, validating FadD32 as a target for antibiotic development that works in the same pathway as the established antibiotic isoniazid. Targeting new steps in well-validated biosynthetic pathways in antitubercular therapy is a powerful strategy that removes much of the usual uncertainty surrounding new targets and in vivo clinical efficacy, while circumventing existing resistance to established targets."xsd:string |
| http://purl.uniprot.org/citations/23798446 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1302114110"xsd:string |
| http://purl.uniprot.org/citations/23798446 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1302114110"xsd:string |
| http://purl.uniprot.org/citations/23798446 | http://purl.uniprot.org/core/author | "Hung D.T."xsd:string |
| http://purl.uniprot.org/citations/23798446 | http://purl.uniprot.org/core/author | "Hung D.T."xsd:string |
| http://purl.uniprot.org/citations/23798446 | http://purl.uniprot.org/core/author | "Shimizu M."xsd:string |
| http://purl.uniprot.org/citations/23798446 | http://purl.uniprot.org/core/author | "Shimizu M."xsd:string |
| http://purl.uniprot.org/citations/23798446 | http://purl.uniprot.org/core/author | "Sacchettini J.C."xsd:string |
| http://purl.uniprot.org/citations/23798446 | http://purl.uniprot.org/core/author | "Sacchettini J.C."xsd:string |
| http://purl.uniprot.org/citations/23798446 | http://purl.uniprot.org/core/author | "Rubin E.J."xsd:string |
| http://purl.uniprot.org/citations/23798446 | http://purl.uniprot.org/core/author | "Rubin E.J."xsd:string |
| http://purl.uniprot.org/citations/23798446 | http://purl.uniprot.org/core/author | "Kawate T."xsd:string |
| http://purl.uniprot.org/citations/23798446 | http://purl.uniprot.org/core/author | "Kawate T."xsd:string |
| http://purl.uniprot.org/citations/23798446 | http://purl.uniprot.org/core/author | "Ioerger T.R."xsd:string |
| http://purl.uniprot.org/citations/23798446 | http://purl.uniprot.org/core/author | "Ioerger T.R."xsd:string |
| http://purl.uniprot.org/citations/23798446 | http://purl.uniprot.org/core/author | "Iwase N."xsd:string |
| http://purl.uniprot.org/citations/23798446 | http://purl.uniprot.org/core/author | "Iwase N."xsd:string |
| http://purl.uniprot.org/citations/23798446 | http://purl.uniprot.org/core/author | "Stanley S.A."xsd:string |
| http://purl.uniprot.org/citations/23798446 | http://purl.uniprot.org/core/author | "Stanley S.A."xsd:string |
| http://purl.uniprot.org/citations/23798446 | http://purl.uniprot.org/core/author | "Aquadro J.A."xsd:string |
| http://purl.uniprot.org/citations/23798446 | http://purl.uniprot.org/core/author | "Aquadro J.A."xsd:string |
| http://purl.uniprot.org/citations/23798446 | http://purl.uniprot.org/core/author | "Clatworthy A.E."xsd:string |
| http://purl.uniprot.org/citations/23798446 | http://purl.uniprot.org/core/author | "Clatworthy A.E."xsd:string |