title: Targeting tuberculosis using structure-guided fragment-based drug design.
abstract: Fragment-based drug discovery is now widely used in academia and industry to obtain small molecule inhibitors for a given target and is established for many fields of research including antimicrobials and oncology. Many molecules derived from fragment-based approaches are already in clinical trials and two - vemurafenib and venetoclax - are on the market, but the approach has been used sparsely in the tuberculosis field. Here, we describe the progress of our group and others, and examine the most recent successes and challenges in developing compounds with antimycobacterial activity.
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge CB21GA, UK.
authors.forename: Vitor
authors.initials: V
authors.lastname: Mendes
authors.affiliation: Department of Biochemistry, University of Cambridge, Cambridge CB21GA, UK. Electronic address: tom@cryst.bioc.cam.ac.uk.
authors.forename: Tom L
authors.initials: TL
authors.lastname: Blundell
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000494:pharmacology / Q000627:therapeutic use; D001426:Bacterial Proteins / Q000378:metabolism; D002473:Cell Wall; D003065:Coenzyme A / Q000378:metabolism; D015195:Drug Design; D005000:Ethionamide / Q000494:pharmacology / Q000627:therapeutic use; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000378:metabolism; D012097:Repressor Proteins / Q000378:metabolism; D013329:Structure-Activity Relationship; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D000995:Antitubercular Agents; D001426:Bacterial Proteins; C481661:EthR protein, Mycobacterium tuberculosis; D012097:Repressor Proteins; D005000:Ethionamide; D003065:Coenzyme A