GGsTop (Synonyms: Nahlsgen) |
Katalog-Nr.GC16612
One-Click Copy Product Info
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γ-Glutamyl-Transpeptidase (GGT)-Inhibitor, neuartig und irreversibel.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 926281-37-0
Sample solution is provided at 25 µL, 10mM.
GGsTop is an irreversible inhibitor of γ-glutamyl transpeptidase (GGT) (Ki = 170μM) [1]. GGsTop covalently binds to the active site of GGT, inhibiting its catalytic activity, thereby regulating the intracellular reduction state, impacting amino acid metabolism, and modulating cellular redox balance [2-3]. GGsTop is primarily used to alleviate liver damage [4].
In human periodontal ligament cells (hPLCs), the proliferation of hPLCs was enhanced after treatment with GGsTOP (0-50μM; 7d) [5]. In HCC-1806 cells, Glutathione activity was inhibited after GGsTOP (0.01-10000nM; 4h) treatment [6].
In cyclophosphamide-induced neutropenic tumor mice model, GGsTop (5mg/kg; ip; 6d) abolishes the tumor growth-promoting effect of granulocyte colony stimulating factor [7]. In Otsuka Long-Evans Tokushima Fatty (OLETF) rats, GGsTop (1mg/kg; iv; single injection) resulted in significant reduction of serum ALT, AST and γ-GT levels [8].
References:
[1]. Han L, Hiratake J, Kamiyama A, et al. Design, synthesis, and evaluation of γ-phosphono diester analogues of glutamate as highly potent inhibitors and active site probes of γ-glutamyl transpeptidase[J]. Biochemistry, 2007, 46(5): 1432-1447.
[2]. Kamiyama A, Nakajima M, Han L, 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[J]. Bioorganic & Medicinal Chemistry, 2016, 24(21): 5340-5352.
[3]. Terzyan S S, Nguyen L T, Burgett A W G, et al. Crystal structures of glutathione-and inhibitor-bound human GGT1: Critical interactions within the cysteinylglycine binding site[J]. Journal of Biological Chemistry, 2021, 296.
[4]. Tamura K, Hayashi N, George J, et al. GGsTop, a novel and specific γ-glutamyl transpeptidase inhibitor, protects hepatic ischemia-reperfusion injury in rats[J]. American Journal of Physiology-Gastrointestinal and Liver Physiology, 2016, 311(2): G305-G312.
[5]. Jiang Y, Wang X, Li Y, et al. GGsTOP increases migration of human periodontal ligament cells in vitro via reactive oxygen species pathway[J]. Molecular Medicine Reports, 2016, 13(5): 3813-3820.
[6]. Hecht F, Zocchi M, Tuttle E T, et al. Catabolism of extracellular glutathione supplies amino acids to support tumor growth[J]. bioRxiv, 2024.
[7]. Xie Z, Kawasaki T, Zhou H, et al. Targeting GGT1 eliminates the tumor-promoting effect and enhanced immunosuppressive function of myeloid-derived suppressor cells caused by G-CSF[J]. Frontiers in Pharmacology, 2022, 13: 873792.
[8]. Kubota R, Hayashi N, Kinoshita K, et al. Inhibition of γ‐glutamyltransferase ameliorates ischaemia‐reoxygenation tissue damage in rats with hepatic steatosis[J]. British Journal of Pharmacology, 2020, 177(22): 5195-5207.
| Cell experiment [1]: | |
Cell lines | Human periodontal ligament cells (hPLCs) |
Preparation Method | Cell viability was measured in hPLCs using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. In brief, hPLCs (2.5×103cells/well) were seeded into 96-well plates and allowed to attach and grow for 24h. The cells were starved overnight and then incubated with 0, 5, 10, 20 or 50μM GGsTOP for 1, 3, 5 and 7 days. The medium was replaced every other day. Then, 20μl MTT was added to each well at the indicated time point and the cells were incubated for 4h. The medium was subsequently removed and 150μl dimethyl sulfoxide was added to each well for 10min. |
Reaction Conditions | 0-50μM; 7d |
Applications | The proliferation of hPLCs was enhanced after treatment with GGsTOP. |
| Animal experiment [2]: | |
Animal models | Cyclophosphamide-induced neutropenic tumor mice model |
Preparation Method | EL4 lymphoma cells (4 × 105 cells/mouse) were injected subcutaneously into the lower right flank of C57BL/6J mice. Seven days after inoculation with EL4 cells, mice were intraperitoneally administered a single dose of CPA (100mg/kg) to create a neutropenic mouse model as described previously. Starting from the same day, experimental mice received intraperitoneal injections of PBS, GGsTop (5mg/kg), and recombinant granulocyte colony stimulating factor (G-CSF, 200μg/kg) for six consecutive days. Before administration of the above reagent, mouse retro-orbital blood (approximately 75μL) was collected for flow cytometry analysis and determining blood cell counts using a Sysmex XT-2000i automated hematology analyzer daily. |
Dosage form | 5mg/kg; ip; 6d |
Applications | GGsTop abolishes the tumor growth-promoting effect of G-CSF. |
References: | |
| Cas No. | 926281-37-0 | SDF | |
| Überlieferungen | Nahlsgen | ||
| Chemical Name | (S)-2-amino-4-((S)-(3-(carboxymethyl)phenoxy)(methoxy)phosphoryl)butanoic acid | ||
| Canonical SMILES | O=[P@](OC)(CC[C@@H](C(O)=O)N)OC1=CC=CC(CC(O)=O)=C1 | ||
| Formula | C13H18NO7P | M.Wt | 331.26 |
| Löslichkeit | <33.13mg/ml in Water; <33.13mg/ml in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.0188 mL | 15.0939 mL | 30.1878 mL |
| 5 mM | 603.8 μL | 3.0188 mL | 6.0376 mL |
| 10 mM | 301.9 μL | 1.5094 mL | 3.0188 mL |
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >95.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 4 reference(s) in Google Scholar.)