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

• DOI: 10.1002/cbic.201800671
• Publication Date: 2018-12-08T06:58:57Z
• Authors: Yuko Shishido; Fumiaki Tomoike; Keiko Kuwata; Haruka Fujikawa; Yoshitaka Sekido; Yuko Murakami‐Tonami; Tomoshi Kameda; Naoko Abe; Yasuaki Kimura; Satoshi Shuto; Hiroshi Abe
• Keywords: GSTP1; Sulfonyl; Conjugate; Glutathione S-transferase; Mechanism of Action

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