GGsTop (Synonyms: Nahlsgen) |
カタログ番号GC16612
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GGsTopはγ-グルタミルトランスペプチダーゼ（GGT）の不可逆的な阻害剤である（Ki = 170μM）。
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はγ-グルタミルトランスペプチダーゼ（GGT）の不可逆的な阻害剤である（Ki = 170μM）[1]。GGsTopはGGTの活性部位に共有結合し、その触媒活性を阻害し、よって細胞内還元状態を制御し、アミノ酸の代謝を影響し、細胞酸化還元のバランスを調節する[2-3]。GGsTopは主に肝臓損傷の軽減に使われる[4]。
ヒト歯周靭帯細胞（hPLCs）で、hPLCsの増殖は、GGsTOP (0-50μM；7日間)の処理後に増強した[5]。HCC-1806細胞で、Glutathioneの活性は、GGsTOP (0.01-10000nM；4時間)の処理後に阻害された[6]。
シクロホスファミド誘発の好中球減少性腫瘍マウスモデルで、GGsTop（5mg/kg；腹腔内注射；6日間）は、顆粒球コロニー刺激因子の腫瘍成功促進作用を阻害する[7]。Otsuka Long-Evans Tokushima Fatty (OLETF)ラットで、GGsTop (1mg/kg；静脈内注射；単回注射)は血清ALT、ASTとγ-GTのレベルを著しく減らした[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.
| 細胞実験[1]: | |
細胞株 | ヒト歯周靭帯細胞（hPLCs） |
準備方法 | 3-(4,5-ジメチルチアゾール-2-イル)-2,5-ジフェニルテトラゾリウム臭化物（MTT）アッセイを使い、細胞の生存率をhPLCsで測定した。手短に言うと、hPLCs (2.5×103個の細胞/ウェル)を96ウェルのプレートに播種し、接着させ、24時間培養した。細胞を一晩中飢餓させ、0、5、10、20または50μMのGGsTOPで1、3、5と7日間培養した。培地を隔日で交換した。その後、指定された時点で、20μl MTTを各ウェルに添加し、細胞を4時間培養した。その後、培地を除去し、150μlのジメチルスルホキシドを各ウェルに10分間添加した。 |
反応条件 | 0-50μM；7日間 |
アプリケーション | hPLCsの増殖は、GGsTOPの処理後増強された。 |
| 動物実験 [2]: | |
動物モデル | シクロホスファミド誘発の好中球減少性腫瘍マウスモデル |
準備方法 | C57BL/6Jマウスの右下脇腹に、EL4リンパ腫細胞（4 × 105個の細胞/マウス）を皮下注射した。EL4細胞の接種の7日後に、マウスにはCPA（100mg/kg）を単回腹腔内注射し、前述の通りに、好中球減少性マウスモデルを作成した。同日から、実験マウスには、PBS、GGsTop (5mg/kg)、組換え顆粒球コロニー刺激因子（G-CSF、200μg/kg）を6日間連続して腹腔内注射した。上記の試薬の投与前、マウス後眼窩血液（約75μL）を毎日採取し、フローサイトメトリー分析を行い、Sysmex XT-2000i自動血液分析装置で血球の数を測定した。 |
投与形態 | 5mg/kg；腹腔内注射；6日間 |
アプリケーション | GGsTopは、G-CSFの腫瘍成長促進作用を阻害する。 |
References: | |
| Cas No. | 926281-37-0 | SDF | |
| 同義語 | 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 |
| 溶解度 | <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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Quality Control & SDS
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- Purity: >95.00% Appearance: A solid
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Average Rating: 5 (Based on Reviews and 4 reference(s) in Google Scholar.)