GGsTop
Products are for research use only. Not for human use. We do not sell to patients.
| Pack Size | Price | Availability | Quantity | Action |
|---|---|---|---|---|
| 1mg | $66.00 | In Stock | 1 | |
| 5mg | $144.00 | In Stock | 1 | |
| 10mg | $225.00 | In Stock | 1 | |
| 25mg | $504.00 | In Stock | 1 |
Citations
2 publicationsPublications from researchers using this productDescription
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.
Protocol
| 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: | |
Product Documents
Chemical Properties
Use stock solutions within 6 months when stored at -80°C or within 1 month when stored at -20°C.
To improve solubility, warm the tube to 37°C and sonicate it for an appropriate period.
CalculatorsMolarity / Dilution / Molecular Weight / Unit Conversion / In Vivo Formulation / Solubility
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