Ezatiostat是一种谷胱甘肽的三肽类似物、选择性的口服活性的谷胱甘肽S-转移酶P1-1（GSTP1）抑制剂。
Cas No.:168682-53-9
Sample solution is provided at 25 µL, 10mM.
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Ezatiostat is a tripeptide analog of glutathione and a selective, orally active inhibitor of glutathione S-transferase P1-1 (GSTP1)[1-2]. By inhibiting GSTP1, Ezatiostat activates JNK, stimulates cell proliferation, and is applicable for research related to myelodysplastic syndromes (MDS)[3-4].
In vitro, Ezatiostat (0-20μM) was used to treat hepatocellular carcinoma cell lines such as Huh7, HepG2, and Hep3B for 72 hours. Ezatiostat directly targeted and inhibited GSTP1 enzyme activity, promoting the accumulation of reactive oxygen species (ROS) and inducing cellular senescence[5]. Ezatiostat (12.5μM) was also combined with the ALK inhibitor crizotinib to treat ALK-translocated lung adenocarcinoma (LUAD) patient-derived organoids (LUAD-OG1) for 14 days. Ezatiostat significantly inhibited tumor growth and enhanced the sensitivity of the organoids to crizotinib[6].
In vivo, Ezatiostat (50mg/kg; i.p.; administered every other day) was administered to an ovariectomized (OVX) mouse model for 1 month. Ezatiostat exacerbated OVX-induced osteoporosis[7]. Ezatiostat (0-30mg/kg; i.p.) was also used to pretreat C57BL/6J mice, which were exposed to alcohol 30 minutes later. Ezatiostat dose-dependently reduced the positive reinforcing effects of alcohol and inhibited nonspecific locomotor activity[8].
References:
[1] Shu G, Chen K, Li J, et al. Galangin alleviated Doxorubicin-induced cardiotoxicity by inhibiting ferroptosis through GSTP1/JNK pathway. Phytomedicine. 2024 Nov;134:155989.
[2] Galili N, Tamayo P, Botvinnik OB, et al. Prediction of response to therapy with ezatiostat in lower risk myelodysplastic syndrome. J Hematol Oncol. 2012 May 6;5:20.
[3] Mahadevan D, Sutton GR. Ezatiostat hydrochloride for the treatment of myelodysplastic syndromes. Expert Opin Investig Drugs. 2015 May;24(5):725-33.
[4] Raza A, Galili N, Smith SE, et al. A phase 2 randomized multicenter study of 2 extended dosing schedules of oral ezatiostat in low to intermediate-1 risk myelodysplastic syndrome. Cancer. 2012 Apr 15;118(8):2138-47.
[5] Zhang Y, Xiao B, Yuan S, et al. Tryptanthrin targets GSTP1 to induce senescence and increases the susceptibility to apoptosis by senolytics in liver cancer cells. Redox Biol. 2024 Oct;76:103323.
[6] Wang SQ, Chen JJ, Jiang Y, et al. Targeting GSTP1 as Therapeutic Strategy against Lung Adenocarcinoma Stemness and Resistance to Tyrosine Kinase Inhibitors. Adv Sci (Weinh). 2023 Mar;10(7):e2205262.
[7] Ji X, Hong J, Yang W, et al. GSTP1-mediated S-glutathionylation of Pik3r1 is a redox hub that inhibits osteoclastogenesis through regulating autophagic flux. Redox Biol. 2023 May;61:102635.
[8] Faccidomo S, Swaim KS, Saunders BL, et al, Eastman VR, Hodge CW. Mining the nucleus accumbens proteome for novel targets of alcohol self-administration in male C57BL/6J mice. Psychopharmacology (Berl). 2018 Jun;235(6):1681-1696.
Ezatiostat是一种谷胱甘肽的三肽类似物、选择性的口服活性的谷胱甘肽S-转移酶P1-1（GSTP1）抑制剂[1-2]。Ezatiostat通过抑制GSTP1导致JNK激活，刺激细胞增殖，可用于骨髓增生异常综合症（MDS）的相关研究[3-4]。
在体外，Ezatiostat（0-20μM）处理Huh7、HepG2和Hep3B等肝癌细胞72小时。Ezatiostat通过直接靶向抑制GSTP1酶活性，促进活性氧（ROS）的累积和细胞衰老[5]。Ezatiostat（12.5μM）与ALK抑制剂克唑替尼（crizotinib）联合处理ALK易位肺腺癌（LUAD）患者来源的类器官（LUAD-OG1）14天。Ezatiostat显著抑制了肿瘤生长，并增强了类器官对克唑替尼的敏感性[6]。
在体内，Ezatiostat（50mg/kg；i.p.；隔日一次）处理卵巢摘除（OVX）小鼠模型1个月。Ezatiostat加剧了OVX诱导的骨质疏松[7]。Ezatiostat（0-30mg/kg；i.p.）预处理C57BL/6J小鼠，30分钟后小鼠接受酒精刺激。Ezatiostat剂量依赖性地减少了酒精的正性强化效应。Ezatiostat可抑制非特异性运动[8]。
| Cell experiment [1]: | |
Cell lines | Huh7, HepG2, and Hep3B hepatocellular carcinoma (HCC) cell lines |
Preparation Method | Huh7, HepG2, and Hep3B cells were cultured under standard conditions. Ezatiostat (0-20μM; 72h) was applied to the cells. |
Reaction Conditions | 0-20μM; 72h. |
Applications | Ezatiostat through direct targeting and inhibition of GSTP1 enzyme activity, induced cellular senescence in HCC cells. This was characterized by positive SA-β-gal staining, reduced Lamin B1, increased expression of p21/p16/p27, and accumulation of ROS, activation of DDR, and secretion of SASP factors. This senescence induction was dependent on the GSTP1/ROS/DDR/NF-κB/SASP axis. |
| Animal experiment [2]: | |
Animal models | Female C57BL/6J mice (13-week-old) were subjected to SHAM or OVX (ovariectomy) surgery to establish a postmenopausal osteoporosis model |
Preparation Method | Mice were randomly divided into groups. Ezatiostat (50mg/kg; i.p) or vehicle (normal saline) was administered to the OVX mice. The mice were sacrificed at the expected endpoint for analysis. |
Dosage form | 50mg/kg; i.p.; administered every other day for 1 month. |
Applications | Ezatiostat treatment exacerbated bone loss in OVX-induced osteoporotic mice, as shown by Micro-CT analysis, which revealed decreased bone mass, lower BV/TV (Bone Volume/Total Volume) and Tb.N (Trabecular Number), and higher Tb.Sp (Trabecular Separation) compared to the OVX-only group. |
References: | |
| Cas No. | 168682-53-9 | SDF | |
| 别名 | TER199;TLK199;Telintra | ||
| 化学名 | ethyl (2S)-2-amino-5-[[(2R)-3-benzylsulfanyl-1-[[(1R)-2-ethoxy-2-oxo-1-phenylethyl]amino]-1-oxopropan-2-yl]amino]-5-oxopentanoate | ||
| Canonical SMILES | CCOC(=O)C(CCC(=O)NC(CSCC1=CC=CC=C1)C(=O)NC(C2=CC=CC=C2)C(=O)OCC)N | ||
| 分子式 | C27H35N3O6S | 分子量 | 529.65 |
| 溶解度 | ≥ 26.5mg/mL in DMSO, ≥ 42.6 mg/mL in EtOH | 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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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.888 mL | 9.4402 mL | 18.8804 mL |
| 5 mM | 377.6 μL | 1.888 mL | 3.7761 mL |
| 10 mM | 188.8 μL | 944 μL | 1.888 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 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 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
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，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
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- Purity: >98.00% Appearance: A solid
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