title: High throughput screening of a library based on kinase inhibitor scaffolds against Mycobacterium tuberculosis H37Rv.
abstract: Kinase targets are being pursued in a variety of diseases beyond cancer, including immune and metabolic as well as viral, parasitic, fungal and bacterial. In particular, there is a relatively recent interest in kinase and ATP-binding targets in Mycobacterium tuberculosis in order to identify inhibitors and potential drugs for essential proteins that are not targeted by current drug regimens. Herein, we report the high throughput screening results for a targeted library of approximately 26,000 compounds that was designed based on current kinase inhibitor scaffolds and known kinase binding sites. The phenotypic data presented herein may form the basis for selecting scaffolds/compounds for further enzymatic screens against specific kinase or other ATP-binding targets in Mycobacterium tuberculosis based on the apparent activity against the whole bacteria in vitro.
authors.affiliation: Southern Research Institute, 2000 Ninth Avenue South, Birmingham, AL 35205, USA. reynolds@SouthernResearch.org
authors.forename: Robert C
authors.initials: RC
authors.lastname: Reynolds
authors.forename: Subramaniam
authors.initials: S
authors.lastname: Ananthan
authors.forename: Ellen
authors.initials: E
authors.lastname: Faaleolea
authors.forename: Judith V
authors.initials: JV
authors.lastname: Hobrath
authors.forename: Cecil D
authors.initials: CD
authors.lastname: Kwong
authors.forename: Clinton
authors.initials: C
authors.lastname: Maddox
authors.forename: Lynn
authors.initials: L
authors.lastname: Rasmussen
authors.forename: Melinda I
authors.initials: MI
authors.lastname: Sosa
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Thammasuvimol
authors.forename: E Lucile
authors.initials: EL
authors.lastname: White
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.forename: John A
authors.initials: JA
authors.lastname: Secrist
mesh_terms: D000995:Antitubercular Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D007155:Immunologic Factors / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000235:genetics; D047428:Protein Kinase Inhibitors / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D054852:Small Molecule Libraries; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy* / Q000235:genetics
chemical_list: D000995:Antitubercular Agents; D007155:Immunologic Factors; D047428:Protein Kinase Inhibitors; D054852:Small Molecule Libraries