論文

査読有り 国際誌
2019年4月1日

A Covalent Inhibitor for Glutathione S-Transferase Pi (GSTP1-1 ) in Human Cells.

Chembiochem : a European journal of chemical biology
  • Yuko Shishido
  • ,
  • Fumiaki Tomoike
  • ,
  • Keiko Kuwata
  • ,
  • Haruka Fujikawa
  • ,
  • Yoshitaka Sekido
  • ,
  • Yuko Murakami-Tonami
  • ,
  • Tomoshi Kameda
  • ,
  • Naoko Abe
  • ,
  • Yasuaki Kimura
  • ,
  • Satoshi Shuto
  • ,
  • Hiroshi Abe

20
7
開始ページ
900
終了ページ
905
記述言語
英語
掲載種別
DOI
10.1002/cbic.201800671

Glutathione S-transferase π (GSTP1-1 ) is overexpressed in many types of cancer and is involved in drug resistance. Therefore, GSTP1-1 is an important target in cancer therapy, and many GST inhibitors have been reported. We had previously developed an irreversible inhibitor, GS-ESF, as an effective GST inhibitor; however, its cellular permeability was too low for it to be used in inhibiting intracellular GST. We have now developed new irreversible inhibitors by introducing sulfonyl fluoride (SF) into chloronitrobenzene (CNB). The mechanism of action was revealed to be that CNBSF first reacts with glutathione (GSH) through an aromatic substitution in the cell, then the sulfonyl group on the GSH conjugate with CNBSF reacts with Tyr108 of GST to form a sulfonyl ester bond. Our new inhibitor irreversible inhibited GSTP1-1 both in vitro and in cellulo with a long duration of action.

リンク情報
DOI
https://doi.org/10.1002/cbic.201800671
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/30548113

エクスポート
BibTeX RIS