title: Stability of Novel Siderophore Cephalosporin S-649266 against Clinically Relevant Carbapenemases.
abstract: To better understand the antibacterial activity of S-649266 against carbapenemase producers, its stability against clinically relevant carbapenemases was investigated. The catalytic efficiencies (kcat/Km) of IMP-1, VIM-2, and L1 for S-649266 were 0.0048, 0.0050, and 0.024 μM(-1) s(-1), respectively, which were more than 260-fold lower than that for meropenem. Only slight hydrolysis of S-649266 against KPC-3 was observed. NDM-1 hydrolyzed meropenem 3-fold faster than S-649266 at 200 μM.
authors.affiliation: Discovery Research Laboratory for Core Therapeutic Areas, Shionogi & Co., Ltd., Osaka, Japan.
authors.forename: Tsukasa
authors.initials: T
authors.lastname: Ito-Horiyama
authors.affiliation: Toho University School of Medicine, Tokyo, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Ishii
authors.affiliation: Discovery Research Laboratory for Core Therapeutic Areas, Shionogi & Co., Ltd., Osaka, Japan.
authors.forename: Akinobu
authors.initials: A
authors.lastname: Ito
authors.affiliation: Discovery Research Laboratory for Core Therapeutic Areas, Shionogi & Co., Ltd., Osaka, Japan takafumi.satou@shionogi.co.jp.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Sato
authors.affiliation: Discovery Research Laboratory for Core Therapeutic Areas, Shionogi & Co., Ltd., Osaka, Japan.
authors.forename: Rio
authors.initials: R
authors.lastname: Nakamura
authors.affiliation: Global Innovation Office, Shionogi & Co., Ltd., Osaka, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Fukuhara
authors.affiliation: Discovery Research Laboratory for Core Therapeutic Areas, Shionogi & Co., Ltd., Osaka, Japan.
authors.forename: Masakatsu
authors.initials: M
authors.lastname: Tsuji
authors.affiliation: Discovery Research Laboratory for Core Therapeutic Areas, Shionogi & Co., Ltd., Osaka, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Yamano
authors.affiliation: Toho University School of Medicine, Tokyo, Japan.
authors.forename: Keizo
authors.initials: K
authors.lastname: Yamaguchi
authors.affiliation: Toho University School of Medicine, Tokyo, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Tateda
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors*; D002511:Cephalosporins / Q000737:chemistry* / Q000494:pharmacology; D004355:Drug Stability; D000077731:Meropenem; D017262:Siderophores / Q000737:chemistry*; D013845:Thienamycins / Q000737:chemistry / Q000494:pharmacology; D001618:beta-Lactamases
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D002511:Cephalosporins; D017262:Siderophores; D013845:Thienamycins; D001618:beta-Lactamases; C063912:carbapenemase; D000077731:Meropenem