Development of Telintra as an Inhibitor of Glutathione S-Transferase P.

Abstract

Glutathione S-transferase P (GSTP) is a component of a complex series of pathways that provide cellular redox homeostasis. It is an abundant protein in certain tumors and is over-expressed in cancer drug resistance. It has diverse cellular functions that include, thiolase activities with small electrophilic agents or susceptible cysteine residues on the protein to mediate S-glutathionylation, and chaperone binding with select protein kinases. Preclinical and clinical testing of a nanomolar inhibitor of GSTP, TLK199 (Telintra; Ezatiostat) has indicated a role for the enzyme in hematopoiesis and utility for the drug in the treatment of patients with myelodysplastic syndrome.

• Authors: Jie Zhang, Zhi-Wei Ye, Yvonne Janssen-Heininger, Danyelle M Townsend, Kenneth D Tew
• Journal: Handbook of experimental pharmacology (Handb Exp Pharmacol) Vol. 264 Pg. 71-91 ( 2021) ISSN: 0171-2004 [Print] Germany
• PMID: 32767141 (Publication Type: Journal Article)

Chemical References

• gamma-Glu-S-BzCys-PhGly diethyl ester
• Glutathione Transferase
• Glutathione

Topics

• Glutathione (analogs & derivatives, metabolism)
• Glutathione Transferase (metabolism)
• Humans
• Neoplasms (drug therapy)
• Protein Binding