New class of competitive inhibitor of bacterial histidine kinases.
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.
Gilmour
Raymond
R
Eli Lilly and Company, Indianapolis, Indiana 46285, USA.
Foster
J Estelle
JE
Sheng
Qin
Q
McClain
Jonathan R
JR
Riley
Anna
A
Sun
Pei-Ming
PM
Ng
Wai-Leung
WL
Yan
Dalai
D
Nicas
Thalia I
TI
Henry
Kenneth
K
Winkler
Malcolm E
ME
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*
D001426:Bacterial Proteins; D004791:Enzyme Inhibitors; D011725:Pyridines; C446540:thienopyridine; D011494:Protein Kinases; D000071677:Histidine Kinase