Biochem/physiol Actions
Gamma-glutamyl transpeptidase (GGT; aka gamma-glutamyl transferase) cleaves the gamma-glutamyl bond of glutathione, making extracellular glutathione available for intracellular use. Elevated intracellular glutathione contributes to resistance of tumors to chemotherapy and radiation. GGT is a therapeutic target for treatment-resistance cancers, as treatment with GGT inhibitors prior to chemotherapy or radiation could sensitize GGT-positive tumors to treatment by decreasing glutathione levels. Previously, all GGT inhibitors have been glutamine analogues, which are competitive for the gamma-glutamyl site. Due to high toxicity, these compounds cannot be used in the clinic. OU749 is the first non-glutamine GGT inhibitor. It is also non-competitive for the gamma-glutamyl site. OU749 inhibits human GGT in an enzyme assay and is much less toxic than other GGT inhibitors, including azaserine (glutamine analogue, Sigma catalog). |
Biochem/physiol Actions
Gamma-glutamyl transpeptidase (GGT; aka gamma-glutamyl transferase) cleaves the gamma-glutamyl bond of glutathione, making extracellular glutathione available for intracellular use. Elevated intracellular glutathione contributes to resistance of tumors to chemotherapy and radiation. GGT is a therapeutic target for treatment-resistance cancers, as treatment with GGT inhibitors prior to chemotherapy or radiation could sensitize GGT-positive tumors to treatment by decreasing glutathione levels. Previously, all GGT inhibitors have been glutamine analogues, which are competitive for the gamma-glutamyl site. Due to high toxicity, these compounds cannot be used in the clinic. OU749 is the first non-glutamine GGT inhibitor. It is also non-competitive for the gamma-glutamyl site. OU749 inhibits human GGT in an enzyme assay and is much less toxic than other GGT inhibitors, including azaserine (glutamine analogue, Sigma catalog). |