GGsTop

Names

[ Name ]:
GGsTop

[Synonym ]:
Benzeneacetic acid, 3-[[(3-amino-3-carboxypropyl)methoxyphosphinyl]oxy]-
2-Amino-4-{[3-(carboxymethyl)phenoxy](methoxy)phosphoryl}butanoic acid

Biological Activity

[Description]:

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].

[Related Catalog]:

Research Areas >> Cardiovascular Disease

Signaling Pathways >> Others >> Others

[Target]

Ki: 170 μM (Human GGT)[1]

[In Vitro]

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].

[In Vivo]

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]. Animal Model: Male rats (9 week old)[3] Dosage: 1 mg/kg Administration: Injected into the inferior vena cava for 12, 24, 48 h Result: Lowered the serum levels of ALT, AST, prevented the increase of serum γ-GT levels in IR-GGsTop group.

[References]

[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.

[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.

[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.

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Boiling Point ]:
557.7±50.0 °C at 760 mmHg

[ Molecular Formula ]:
C₁₃H₁₈NO₇P

[ Molecular Weight ]:
331.26

[ Flash Point ]:
291.1±30.1 °C

[ Exact Mass ]:
331.082092

[ PSA ]:
145.96000

[ LogP ]:
-0.66

[ Vapour Pressure ]:
0.0±1.6 mmHg at 25°C

[ Index of Refraction ]:
1.559

[ Storage condition ]:
-20°C