GGsTop
(Synonyms: Nahlsgen) 目录号 : GC16612GGsTop是γ-谷氨酰转肽酶（GGT）的不可逆抑制剂（Ki = 170μM）。
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.
GGsTop是γ-谷氨酰转肽酶（GGT）的不可逆抑制剂（Ki = 170μM） [1]。GGsTop与GGT的活性位点共价结合，抑制其催化活性，从而调节细胞内还原状态，影响氨基酸代谢，并调节细胞氧化还原平衡 [2-3]。GGsTop 主要用于缓解肝损伤 [4]。
在人牙周膜细胞（hPLC）中，GGsTOP（0-50μM；7d）处理后，hPLC的增殖得到增强 [5]。在HCC-1806细胞中，GGsTOP（0.01-10000nM；4h）处理后，谷胱甘肽活性受到抑制 [6]。
在环磷酰胺诱发的中性粒细胞减少性肿瘤小鼠模型中，GGsTop（5mg/kg；ip；6d）可消除粒细胞集落刺激因子的促肿瘤生长作用 [7]。在大冢Long-Evans Tokushima Fatty（OLETF）大鼠中，GGsTop（1mg/kg；iv；单次注射）可显著降低血清ALT、AST和γ-GT水平 [8]。
| 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 | |
| 别名 | Nahlsgen | ||
| 化学名 | (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 | ||
| 分子式 | C13H18NO7P | 分子量 | 331.26 |
| 溶解度 | <33.13mg/ml in Water; <33.13mg/ml in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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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 |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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2.
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Quality Control & SDS
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- Purity: >95.00%
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