Physicochemical Properties
| Molecular Formula | C13H18NO7P |
| Molecular Weight | 331.26 |
| Exact Mass | 331.082 |
| CAS # | 926281-37-0 |
| PubChem CID | 23582776 |
| Appearance | White to off-white solid powder |
| Density | 1.4±0.1 g/cm3 |
| Boiling Point | 557.7±50.0 °C at 760 mmHg |
| Flash Point | 291.1±30.1 °C |
| Vapour Pressure | 0.0±1.6 mmHg at 25°C |
| Index of Refraction | 1.559 |
| LogP | -0.66 |
| Hydrogen Bond Donor Count | 3 |
| Hydrogen Bond Acceptor Count | 8 |
| Rotatable Bond Count | 9 |
| Heavy Atom Count | 22 |
| Complexity | 442 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | NTFPDEDRMYYPAC-UHFFFAOYSA-N |
| 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) |
| Chemical Name | 2-amino-4-[[3-(carboxymethyl)phenoxy]-methoxyphosphoryl]butanoic acid |
| Synonyms | GGs Top; GGs-Top; GGsTop |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| 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. |
| 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]. |
| 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. |
| References |
[1]. 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]. 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]. 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. |
| Additional Infomation | Ggstop is an alpha-amino acid. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~301.88 mM) |
| 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. 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. 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 corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| 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 |