AG205, a novel agent directed against FabK of Streptococcus pneumoniae.
AG205 was identified from high-throughput screening as a potent inhibitor of FabK, the enoyl-ACP reductase in Streptococcus pneumoniae. Specific inhibition of lipid biosynthesis in a macromolecular biosynthesis assay and identification of an Ala141Ser substitution in FabK from spontaneous AG205-resistant mutants indicated that AG205 exerts antibacterial activity against S. pneumoniae through the specific inhibition of FabK.
Takahata
Sho
S
Pharmaceutical Research Center, Meiji Seika Kaisha Ltd., Kohoku-ku, Yokohama 222-8567, Japan. sho_takahata@meiji.co.jp
Iida
Maiko
M
Osaki
Yumi
Y
Saito
Jun
J
Kitagawa
Hideo
H
Ozawa
Tomohiro
T
Yoshida
Takuji
T
Hoshiko
Shigeru
S
D019943:Amino Acid Substitution; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH) / Q000037:antagonists & inhibitors*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D004926:Escherichia coli / Q000235:genetics; D005798:Genes, Bacterial; D006801:Humans; D020128:Inhibitory Concentration 50; D050155:Lipogenesis / Q000187:drug effects; D008826:Microbial Sensitivity Tests / Q000379:methods; D015394:Molecular Structure; D012694:Serine / Q000378:metabolism; D013296:Streptococcus pneumoniae / Q000187:drug effects / Q000201:enzymology* / Q000254:growth & development / Q000302:isolation & purification; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology*
C513963:AG205; D000900:Anti-Bacterial Agents; D004791:Enzyme Inhibitors; D013844:Thiazoles; D012694:Serine; D050753:Enoyl-(Acyl-Carrier-Protein) Reductase (NADH)