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| Targets |
GGsTop targets gamma-glutamyltransferase (GGT), a cell surface enzyme that catalyzes the hydrolysis of glutathione and the transfer of gamma-glutamyl groups to amino acids and peptides. By inhibiting GGT, GGsTop blocks the gamma-glutamyl cycle, which is involved in amino acid transport and glutathione homeostasis. The compound's selectivity for GGT over other enzymes makes it a valuable tool for studying GGT biology.
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| ln Vitro |
GGsTop, also known as Nahlsgen or compound 5a, is a strong, extremely selective, and irreversible inhibitor of γ-glutamyl transpeptidase (GGT), exhibiting a Ki of 170 μM for human GGT [1]. GGsTop demonstrates a pKa of 9.71 and Kons against the GGT of E. coli and humans, which are 150±10 and 51±3 M-1 s-1, respectively[1][2]. GGsTop is a non-toxic substance that, at 1 mM, totally inhibits WT human GGT in less than a minute [2]. However, it is less efficient against the K562S mutant.
In vitro, GGsTop is a potent inhibitor of gamma-glutamyltransferase activity. The compound's inhibitory potency has been characterized in enzymatic assays using purified GGT or cell membrane preparations. GGsTop effectively blocks GGT-mediated hydrolysis of glutathione and transfer of gamma-glutamyl groups. Its effects on glutathione metabolism and cellular redox status have been studied in various cell types. |
| ln Vivo |
Rats' ALT, AST, and γ-GT levels can be decreased by GGsTop (1 mg/kg) at 12, 24, and 48 hours following ischemia-reperfusion [3]. Moreover, GGsTop can lessen rat liver necrosis and the generation of 4-HNE and TNF-α [3].
In vivo, GGsTop has been used to study the role of GGT in various physiological and pathological processes. By inhibiting GGT, the compound modulates glutathione metabolism and amino acid transport in animal models. Its effects on oxidative stress, inflammation, and other GGT-related processes have been investigated. Specific dosing regimens and detailed efficacy data are available in the scientific literature. |
| Enzyme Assay |
In vitro enzyme assays for GGsTop involve measuring the inhibition of gamma-glutamyltransferase activity using purified enzyme preparations or cell membrane fractions. The compound is incubated with GGT and a chromogenic or fluorogenic substrate (e.g., gamma-glutamyl-p-nitroanilide), and the rate of substrate hydrolysis is measured spectrophotometrically. The IC50 value is determined from dose-response curves. Selectivity against other enzymes is assessed using broad screening panels.
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| Cell Assay |
In vitro cell-based assays for GGsTop involve treating cells with the compound to assess its effects on GGT activity, glutathione levels, and cellular redox status. Cells are treated with GGsTop at various concentrations, and GGT activity is measured using cell lysates or intact cells. Glutathione levels (GSH and GSSG) are measured using biochemical assays. Cellular redox status is assessed by measuring reactive oxygen species levels. These assays characterize the compound's cellular effects.
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| Animal Protocol |
Animal/Disease Models: Male rats (9 weeks old) [3]
Doses: 1 mg/kg Route of Administration: Inferior vena cava injection for 12, 24, 48 hrs (hrs (hours)) Experimental Results: Reduce serum ALT and AST levels, prevent serum elevation IR-GGsTop γ-GT levels in the group. In vivo animal experiments for GGsTop have been conducted in models of oxidative stress, inflammation, and other GGT-related conditions. Animals are treated with GGsTop via injection, and GGT activity is measured in tissues. Glutathione levels and oxidative stress markers are assessed. Efficacy endpoints depend on the specific model being studied. These studies have helped elucidate the role of GGT in various physiological and pathological processes. |
| ADME/Pharmacokinetics |
GGsTop has a molecular weight and formula consistent with small-molecule GGT inhibitors. It is typically dissolved in DMSO for in vitro studies and formulated for in vivo administration. The compound's solubility and stability properties are characteristic of small-molecule inhibitors. Specific pharmacokinetic data such as absorption, distribution, metabolism, and elimination are not extensively reported. The compound is typically stored under recommended conditions for research compounds.
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| Toxicity/Toxicokinetics |
Specific toxicity data for GGsTop is not extensively reported. As a GGT inhibitor, its safety profile is related to its effects on glutathione metabolism and the gamma-glutamyl cycle. The compound is generally well-tolerated in preclinical studies at concentrations used for GGT inhibition. Comprehensive toxicological studies would be required for therapeutic development. Standard safety precautions should be taken when handling the compound in research settings.
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| References |
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| Additional Infomation |
Ggstop is an α-amino acid.
GGsTop is a potent and selective inhibitor of gamma-glutamyltransferase (GGT) used as a tool compound for studying GGT biology. By inhibiting GGT, GGsTop blocks the gamma-glutamyl cycle, which is involved in amino acid transport and glutathione homeostasis. The compound has been used to study the role of GGT in oxidative stress, inflammation, and various disease states. GGsTop is a valuable tool for GGT-related research. |
| Molecular Formula |
C13H18NO7P
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|---|---|
| Molecular Weight |
331.26
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| Exact Mass |
331.082
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| CAS # |
926281-37-0
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| PubChem CID |
23582776
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
557.7±50.0 °C at 760 mmHg
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| Flash Point |
291.1±30.1 °C
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| Vapour Pressure |
0.0±1.6 mmHg at 25°C
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| Index of Refraction |
1.559
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| LogP |
-0.66
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
22
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| Complexity |
442
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
NTFPDEDRMYYPAC-UHFFFAOYSA-N
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| InChi Code |
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)
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| Chemical Name |
2-amino-4-[[3-(carboxymethyl)phenoxy]-methoxyphosphoryl]butanoic acid
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| Synonyms |
GGs Top; GGs-Top; GGsTop
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~301.88 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.55 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.55 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (7.55 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0188 mL | 15.0939 mL | 30.1878 mL | |
| 5 mM | 0.6038 mL | 3.0188 mL | 6.0376 mL | |
| 10 mM | 0.3019 mL | 1.5094 mL | 3.0188 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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