GGsTop

• CAT Number: I010961
• CAS Number: 926281-37-0
• Molecular Formula: C13H18NO7P
• Molecular Weight: 331.26
• Purity: ≥95%
• Synonyms: 2-amino-4-[[3-(carboxymethyl)phenoxy]-methoxyphosphoryl]butanoic acid
• InChI: InChI=1S/C13H18NO7P/c1-20-22(19,6-5-11(14)13(17)18)21-10-4-2-3-9(7-10)8-12(15)16/h2-4,7,11H,5-6,8,14H2,1H3,(H,15,16)(H,17,18)
• InChIKey: NTFPDEDRMYYPAC-UHFFFAOYSA-N
• SMILES: COP(=O)(CCC(C(=O)O)N)OC1=CC=CC(=C1)CC(=O)O

GGsTop (Nahlsgen) is a potent, non-toxic, highly selective and irreversible γ−glutamyl transpeptidase (GGT) inhibitor, with a Ki of 170 μM for Human GGT. GGsTop shows a pKa of 9.71, also exhibits Kons of 150±10 and 51±3 M-1 s-1 against E.coli GGT and human GGT, respectively[1][2]. GGsTop protects hepatic ischemia-reperfusion injury in rat model[3].
GGsTop (Nahlsgen; Compound 5a) is a potent, highly selective and irreversible γ?glutamyl transpeptidase (GGT) inhibitor, with a Ki of 170 μM for Human GGT[1]. GGsTop shows pKa of 9.71, also exhibits Kons of 150±10 and 51±3 M-1 s-1 against E.coli GGT and human GGT, respectively[1][2].
GGsTop is non-toxic compound, completely inhibits WT human GGT in 1 min at 1 mM, but less potent against the K562S mutant[2].
GGsTop (1 mg/kg) lowers levels of ALT, AST, γ-GT at 12, 24, and 48 h after ischemia-reperfusion in rats[3].
GGsTop also reduces 4-HNE and TNF-α production, and decreases hepatic necrosis in rats[3].

Reference

[1]. Han L, et al. Design, synthesis, and evaluation of gamma-phosphono diester analogues of glutamate as highly potent inhibitors and active site probes of gamma-glutamyl transpeptidase. Biochemistry. 2007 Feb 6;46(5):1432-47.
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[2]. Kamiyama A, et al. Phosphonate-based irreversible inhibitors of human γ-glutamyl transpeptidase (GGT). GGsTop is a non-toxic and highly selective inhibitor with critical electrostatic interaction with an active-site residue Lys562 for enhanced inhibitory activity. Bioorg Med Chem. 2016 Nov 1;24(21):5340-5352.
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[3]. Tamura K, et al. GGsTop, a novel and specific γ-glutamyl transpeptidase inhibitor, protects hepatic ischemia-reperfusion injury in rats. Am J Physiol Gastrointest Liver Physiol. 2016 Aug 1;311(2):G305-12.
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