Acivicin hydrochloride

Acivicin is a glutamine analog that irreversibly inhibits glutamine-dependent amidotransferases involved in nucleotide and amino acid biosynthesis (K_is = 10 and 560 μM for anthranilate synthase and glutamate synthase, respectively).^1,2 It also reversibly inhibits γ-glutamyl transpeptidase.^3,4 Acividin has been used to elucidate aspects of glutathione metabolism and has known anti-tumorigenic activity.^5,6,2,7

1.Tso, J.Y., Bower, S.G., and Zalkin, H.Mechanism of inactivation of glutamine amidotransferases by the antitumor drug L-(αS, 5S)-α-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (AT-125)J. Biol. Chem.255(14)6734-6738(1980) 2.Lyons, S.D., Sant, M.E., and Christopherson, R.I.Cytotoxic mechanisms of glutamine antagonists in mouse L1210 leukemiaJ. Biol. Chem.265(19)11377-11381(1990) 3.Stole, E., Smith, T.K., Manning, J.M., et al.Interaction of γ-glutamyl transpeptidase with acivicinJ. Biol. Chem.269(34)21435-21439(1994) 4.Smith, T.K., Ikeda, Y., Fujii, J., et al.Different sites of acivicin binding and inactivation of γ-glutamyl transpeptidasesProc. Natl. Acad. Sci. USA922360-2364(1995) 5.Griffith, O.W., and Meister, A.Excretion of cysteine and γ-glutamylcysteine moieties in human and experimental animal γ-glutamyl transpeptidase deficiencyProc. Natl. Acad. Sci. USA77(6)3384-3387(1980) 6.Meck, R.A., Clubb, K.J., Allen, L.M., et al.Inhibition of cell cycle progression of human pancreatic carcinoma cells in vitro by L-(αS,5S)-α-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid, acivicin (NSC 163501)Cancer Res.414547-4553(1981) 7.Willoughby, L.F., Schlosser, T., Manning, S.A., et al.An in vivo large-scale chemical screening platform using Drosophila for anti-cancer drug discoveryDis. Model. Mech.6(2)521-529(2012)