title: New class of competitive inhibitor of bacterial histidine kinases.
abstract: Bacterial histidine kinases have been proposed as targets for the discovery of new antibiotics, yet few specific inhibitors of bacterial histidine kinases have been reported. We report here a novel thienopyridine (TEP) compound that inhibits bacterial histidine kinases competitively with respect to ATP but does not comparably inhibit mammalian serine/threonine kinases. Although it partitions into membranes and does not inhibit the growth of bacterial or mammalian cells, TEP could serve as a starting compound for a new class of histidine kinase inhibitors with antibacterial activity.
authors.affiliation: Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
authors.forename: Raymond
authors.initials: R
authors.lastname: Gilmour
authors.forename: J Estelle
authors.initials: JE
authors.lastname: Foster
authors.forename: Qin
authors.initials: Q
authors.lastname: Sheng
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: McClain
authors.forename: Anna
authors.initials: A
authors.lastname: Riley
authors.forename: Pei-Ming
authors.initials: PM
authors.lastname: Sun
authors.forename: Wai-Leung
authors.initials: WL
authors.lastname: Ng
authors.forename: Dalai
authors.initials: D
authors.lastname: Yan
authors.forename: Thalia I
authors.initials: TI
authors.lastname: Nicas
authors.forename: Kenneth
authors.initials: K
authors.lastname: Henry
authors.forename: Malcolm E
authors.initials: ME
authors.lastname: Winkler
mesh_terms: D001426:Bacterial Proteins / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D000071677:Histidine Kinase; D011494:Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D011725:Pyridines; C446540:thienopyridine; D011494:Protein Kinases; D000071677:Histidine Kinase