論文

査読有り
2010年

Design of Novel Hypoxia-Targeting IDO Hybrid Inhibitors Conjugated with an Unsubstituted L-TRP as an IDO Affinity Moiety

OXYGEN TRANSPORT TO TISSUE XXXI
  • Hitomi Nakashima
  • ,
  • Kazuhiro Ikkyu
  • ,
  • Kouichiro Nakashima
  • ,
  • Keiichiro Sano
  • ,
  • Yoshihiro Uto
  • ,
  • Eiji Nakata
  • ,
  • Hideko Nagasawa
  • ,
  • Hiroshi Sugimoto
  • ,
  • Yoshitsugu Shiro
  • ,
  • Yoshinori Nakagawa
  • ,
  • Hitoshi Hori

662
開始ページ
415
終了ページ
421
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1007/978-1-4419-1241-1_60
出版者・発行元
SPRINGER-VERLAG BERLIN

We presented here design, syntheses and inhibitory activities of novel hypoxia-targeting IDO hybrid inhibitors conjugated with an unsubstituted L-Trp as an IDO affinity moiety without inhibitor 1MT, such as L-Trp-TPZ hybrids 1 (TX-2274), 2 (UTX-3), 3 (UTX-4), and 4 (UTX-2). TPZ-monoxide hybrids 1 and 3 were good competitive IDO inhibitors, while TPZ hybrids 2 and 4 were uncompetitive IDO inhibitors. Among them TPZ-monoxide hybrid 1 have the strongest IDO inhibitory activity. It suggests that TPZ-monoxide hybrids 1 and 3 are able to bind the active site of IDO, TPZ hybrids 2 and 4 are able to bind the enzyme-substrate complex. We proposed the possible mechanism of action of TPZ hybrid 2 that may first affect as a hypoxic cytotoxin, and then metabolized to TPZ-monoxide hybrid 1, which may do as an IDO inhibitor more effectively than its parent TPZ hybrid 2.

Web of Science ® 被引用回数 : 4

リンク情報
DOI
https://doi.org/10.1007/978-1-4419-1241-1_60
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/20204824
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000276395900060&DestApp=WOS_CPL