OU749 is a competitive inhibitor of γ-glutamyl transpeptidase (GGT) [1].
Expression of γ-glutamyl transpeptidase (GGT) in tumors contributes to the resistance to radiation and chemotherapy. GGT is inhibited by glutamine analogues which compete with the substrate for the γ-glutamyl binding site [1].
OU749 inhibited human kidney GGT with an intrinsic Ki of 17.6 M [1]. In 786-O cells, a human renal tumor cell line, OU749 showed more than 150-fold less toxic than the GGT inhibitor acivicin toward dividing cells. OU749 inhibited GGT isolated from human kidney in a dose-dependent manner [1]. OU749 was 7-fold less potent as inhibitor of GGT isolated from rat kidney and 10-fold less potent inhibiting GGT from mouse kidney [1]. OU749 did not inhibit degradation of glutathione by GGT from rat kidney. Inhibition of GGT by OU749 is species-specific [1]. OU749 showed no inhibitory effect on GGT from pig cells. OU749 inhibited human GGT expressed in mouse fibroblasts by a similar extent to the GGT from human cells, indicated that the species specificity was determined by differences in the primary structure of the protein rather than species-specific, post-translational modifications [1].
Reference:
[1] King J B, West M B, Cook P F, et al. A novel, species-specific class of uncompetitive inhibitors of γ-glutamyl transpeptidase[J]. Journal of Biological Chemistry, 2009, 284(14): 9059-9065.