title: Release of 50 new, drug-like compounds and their computational target predictions for open source anti-tubercular drug discovery.
abstract: As a follow up to the antimycobacterial screening exercise and the release of GSK´s first Tres Cantos Antimycobacterial Set (TCAMS-TB), this paper presents the results of a second antitubercular screening effort of two hundred and fifty thousand compounds recently added to the GSK collection. The compounds were further prioritized based on not only antitubercular potency but also on physicochemical characteristics. The 50 most attractive compounds were then progressed for evaluation in three different predictive computational biology algorithms based on structural similarity or GSK historical biological assay data in order to determine their possible mechanisms of action. This effort has resulted in the identification of novel compounds and their hypothesized targets that will hopefully fuel future TB drug discovery and target validation programs alike.
authors.affiliation: Diseases of the Developing World, GlaxoSmithKline, Tres Cantos, Madrid, Spain.
authors.forename: María Jose
authors.initials: MJ
authors.lastname: Rebollo-Lopez
authors.affiliation: Diseases of the Developing World, GlaxoSmithKline, Tres Cantos, Madrid, Spain.
authors.forename: Joël
authors.initials: J
authors.lastname: Lelièvre
authors.affiliation: Diseases of the Developing World, GlaxoSmithKline, Tres Cantos, Madrid, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Alvarez-Gomez
authors.affiliation: Diseases of the Developing World, GlaxoSmithKline, Tres Cantos, Madrid, Spain.
authors.forename: Julia
authors.initials: J
authors.lastname: Castro-Pichel
authors.affiliation: Genome Biology Group, Centre Nacional d'Anàlisi Genòmica (CNAG), Barcelona, Spain.|Gene Regulation Stem Cells and Cancer Program, Centre for Genomic Regulation (CRG), Barcelona, Spain.
authors.forename: Francisco
authors.initials: F
authors.lastname: Martínez-Jiménez
authors.affiliation: European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI), Hinxton, Cambridge, United Kingdom.
authors.forename: George
authors.initials: G
authors.lastname: Papadatos
authors.affiliation: Computational Biology, Quantitative Sciences, GlaxoSmithKline, Collegeville, Pennsylvania, United States of America.
authors.forename: Vinod
authors.initials: V
authors.lastname: Kumar
authors.affiliation: Centro de Investigación Básica, CSci Computational Chemistry, GlaxoSmithKline, Tres Cantos, Madrid, Spain.
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Colmenarejo
authors.affiliation: European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI), Hinxton, Cambridge, United Kingdom.
authors.forename: Grace
authors.initials: G
authors.lastname: Mugumbate
authors.affiliation: Computational Biology, Quantitative Sciences, GlaxoSmithKline, Collegeville, Pennsylvania, United States of America.
authors.forename: Mark
authors.initials: M
authors.lastname: Hurle
authors.affiliation: Centro de Investigación Básica, Platform Technology & Science, GlaxoSmithKline, Tres Cantos, Madrid, Spain.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Barroso
authors.affiliation: CSC Medicinal Chemistry, Medicines Research Centre, GlaxoSmithKline, Stevenage, Hertfordshire, United Kingdom.
authors.forename: Rob J
authors.initials: RJ
authors.lastname: Young
authors.affiliation: Diseases of the Developing World, GlaxoSmithKline, Tres Cantos, Madrid, Spain.
authors.forename: María
authors.initials: M
authors.lastname: Martinez-Hoyos
authors.affiliation: Diseases of the Developing World, GlaxoSmithKline, Tres Cantos, Madrid, Spain.
authors.forename: Rubén
authors.initials: R
authors.lastname: González del Río
authors.affiliation: Diseases of the Developing World, GlaxoSmithKline, Tres Cantos, Madrid, Spain.
authors.forename: Robert H
authors.initials: RH
authors.lastname: Bates
authors.affiliation: Diseases of the Developing World, GlaxoSmithKline, Tres Cantos, Madrid, Spain.
authors.forename: Eva Maria
authors.initials: EM
authors.lastname: Lopez-Roman
authors.affiliation: Diseases of the Developing World, GlaxoSmithKline, Tres Cantos, Madrid, Spain.
authors.forename: Alfonso
authors.initials: A
authors.lastname: Mendoza-Losana
authors.affiliation: Computational Biology, Quantitative Sciences, GlaxoSmithKline, Collegeville, Pennsylvania, United States of America.
authors.forename: James R
authors.initials: JR
authors.lastname: Brown
authors.affiliation: Centro de Investigación Básica, Platform Technology & Science, GlaxoSmithKline, Tres Cantos, Madrid, Spain.
authors.forename: Emilio
authors.initials: E
authors.lastname: Alvarez-Ruiz
authors.affiliation: Genome Biology Group, Centre Nacional d'Anàlisi Genòmica (CNAG), Barcelona, Spain.|Gene Regulation Stem Cells and Cancer Program, Centre for Genomic Regulation (CRG), Barcelona, Spain.|Institució Catalana de Recerca i Estudis Avançats (ICREA), Barcelona, Spain.
authors.forename: Marc A
authors.initials: MA
authors.lastname: Marti-Renom
authors.affiliation: European Molecular Biology Laboratory-European Bioinformatics Institute (EMBL-EBI), Hinxton, Cambridge, United Kingdom.
authors.forename: John P
authors.initials: JP
authors.lastname: Overington
authors.affiliation: Diseases of the Developing World, GlaxoSmithKline, Tres Cantos, Madrid, Spain.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Cammack
authors.affiliation: Diseases of the Developing World, GlaxoSmithKline, Tres Cantos, Madrid, Spain.
authors.forename: Lluís
authors.initials: L
authors.lastname: Ballell
authors.affiliation: Diseases of the Developing World, GlaxoSmithKline, Tres Cantos, Madrid, Spain.
authors.forename: David
authors.initials: D
authors.lastname: Barros-Aguire
mesh_terms: D000465:Algorithms; D000995:Antitubercular Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D019295:Computational Biology / Q000379:methods; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods; D056945:Hep G2 Cells; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects*
chemical_list: D000995:Antitubercular Agents