title: Learning from the past for TB drug discovery in the future.
abstract: Tuberculosis drug discovery has shifted in recent years from a primarily target-based approach to one that uses phenotypic high-throughput screens. As examples of this, through our EU-funded FP7 collaborations, New Medicines for Tuberculosis was target-based and our more-recent More Medicines for Tuberculosis project predominantly used phenotypic screening. From these projects we have examples of success (DprE1) and failure (PimA) going from drug to target and from target to drug, respectively. It is clear that we still have much to learn about the drug targets and the complex effects of the drugs on Mycobacterium tuberculosis. We propose a more integrated approach that learns from earlier drug discovery efforts that could help to move drug discovery forward.
authors.affiliation: Department of Biochemistry, Faculty of Natural Sciences, Comenius University in Bratislava, Mlynská dolina, Ilkovičova 6, 84215 Bratislava, Slovakia.
authors.forename: Katarína
authors.initials: K
authors.lastname: Mikušová
authors.affiliation: Collaborative Drug Discovery, Inc., 1633 Bayshore Highway, Suite 342, Burlingame, CA 94010, USA; Collaborations in Chemistry, 5616 Hilltop Needmore Road, Fuquay Varina, NC 27526, USA. Electronic address: ekinssean@yahoo.com.
authors.forename: Sean
authors.initials: S
authors.lastname: Ekins
mesh_terms: D000429:Alcohol Oxidoreductases / Q000378:metabolism; D000818:Animals; D000995:Antitubercular Agents; D001426:Bacterial Proteins / Q000378:metabolism; D055808:Drug Discovery; D006801:Humans; D000069550:Machine Learning; D008364:Mannosyltransferases / Q000378:metabolism; D014376:Tuberculosis / Q000188:drug therapy
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; D000429:Alcohol Oxidoreductases; C583625:DprE1 protein, Mycobacterium tuberculosis; D008364:Mannosyltransferases