Z-IETD-FMK (Synonyms: Benzyloxycarbonyl-Ile-Glu(OMe)-Thr-Asp(OMe)-fluoromethylketone, Z-Ile-Glu(OMe)-Thr-Asp(OMe)-FMK) |
| カタログ番号GC12407 |
Z-IETD-FMK (Z-IE(OMe)TD(OMe)-FMK)は、選択的で細胞通過性のカスパーゼ-8の阻害剤である。
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 210344-98-2
Sample solution is provided at 25 µL, 10mM.
Z-IETD-FMK (Z-IE(OMe)TD(OMe)-FMK)は、選択的で細胞通過性のカスパーゼ-8の阻害剤である[1]。カスパーゼ-8はシスチンプロテアーゼファミリーのメンバーで、アポトーシスとサイトカインのプロセスに関与する[2]。Z-IETD-FMKはグランザイムBの阻害剤でもある[3]。
試験管内実験で、Z-IETD-FMK (100μM)で末梢血単核細胞(PBMCs)を24時間処理した結果、マイトジェン誘発性T細胞の増殖を著しく阻害し、N活性化T細胞でF-κB RelA (p65)の核転座を遮断した[4]。
生体内実験では、Z-IETD-FMK (5mg/kg)でSHIP1−/−マウスを3週間腹腔内注射した結果、マウスの小腸と肺の解剖学的病理学的特徴を著しく減らし、生存CD3+ T細胞の数を著しく回復させ、溶媒で処理されたマウスはT細胞の欠乏を示した[5]。Z-IETD-FMK (0.5μg)を肺癌のマウスに気管内注射した結果、増殖細胞の数、肺腫瘍の形成と肺腫瘍病巣の数を著しく減らし、Ki-67-陽性の細胞を減らし、気管支肺胞液(BAL)におけるIL-6、TNF-αとIL-18のレベルを減らした[6]。
References:
[1] Xu J, Tan Z C, Shen Z Y, et al. Cordyceps cicadae polysaccharides inhibit human cervical cancer hela cells proliferation via apoptosis and cell cycle arrest[J]. Food and Chemical Toxicology, 2021, 148: 111971.
[2] Tummers B, Green D R. Caspase‐8: regulating life and death[J]. Immunological reviews, 2017, 277(1): 76-89.
[3] Toda H, Yabu T, Shiba H, et al. Evaluating antigen-specific cytotoxicity of CD8+ T cells in fish by granzyme B-like activity[J]. Veterinary immunology and immunopathology, 2011, 141(1-2): 168-172.
[4] Lawrence C P, Chow S C. Suppression of human T cell proliferation by the caspase inhibitors, z-VAD-FMK and z-IETD-FMK is independent of their caspase inhibition properties[J]. Toxicology and applied pharmacology, 2012, 265(1): 103-112.
[5] Park M Y, Srivastava N, Sudan R, et al. Impaired T-cell survival promotes mucosal inflammatory disease in SHIP1-deficient mice[J]. Mucosal immunology, 2014, 7(6): 1429-1439.
[6] Terlizzi M, Di Crescenzo V G, Perillo G, et al. Pharmacological inhibition of caspase‐8 limits lung tumour outgrowth[J]. British Journal of Pharmacology, 2015, 172(15): 3917-3928.
| 細胞実験[1]: | |
細胞株 | 末梢血単核細胞(PBMCs) |
準備方法 | 5μg/mlの抗CD3 mAbと2.5μg/mlの抗CD28 mAbの共同刺激、、または5μg/mlの植物性血球凝集素(PHA)のみで24時間処理のあと、PBMCにおけるT細胞の増殖を、様々な濃度の(50, 100μM)Z-VAD-FMKとZ-IETD-FMKのある/ない状態で測定した。[3H]-チミジンの取り込みを使い、T細胞の増殖を測定した。 |
反応条件 | 50, 100μM；24時間 |
アプリケーション | Z-VAD-FMKとZ-IETD-FMKはマイトジェン誘発性T細胞の増殖に対する効果は同じで、よい高い濃度(100μM)ではT細胞の増殖を阻害できた。 |
| 動物実験 [2]: | |
動物モデル | SHIP1−/−マウス |
準備方法 | SHIP1−/−マウスにZ-IETD-FMK (5mg/kg)または溶媒(DMSO)を3週間、週に3回腹腔内注射した。注射の開始から三週間後、小腸と肺を摘出し、リンパ球を分離し、抗CD3とDAPI染料で染色した。 |
投与形態 | 5mg/kg、3週間、週に三回；腹腔内投与 |
アプリケーション | Z-IETD-FMKでSHIP1−/−マウスを処理した結果、小腸と肺における解剖的病変を著しく減らし、生存できるCD3+ T細胞の数を著しく回復させ、溶媒で処理されたマウスはT細胞の欠乏を示した。 |
References: | |
| Cas No. | 210344-98-2 | SDF | |
| 同義語 | Benzyloxycarbonyl-Ile-Glu(OMe)-Thr-Asp(OMe)-fluoromethylketone, Z-Ile-Glu(OMe)-Thr-Asp(OMe)-FMK | ||
| Chemical Name | methyl 5-[[1-[(5-fluoro-1-methoxy-1,4-dioxopentan-3-yl)amino]-3-hydroxy-1-oxobutan-2-yl]amino]-4-[[3-methyl-2-(phenylmethoxycarbonylamino)pentanoyl]amino]-5-oxopentanoate | ||
| Canonical SMILES | CCC(C)C(C(=O)NC(CCC(=O)OC)C(=O)NC(C(C)O)C(=O)NC(CC(=O)OC)C(=O)CF)NC(=O)OCC1=CC=CC=C1 | ||
| Formula | C30H43FN4O11 | M.Wt | 654.68 |
| 溶解度 | ≥ 32.734mg/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. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 1.5275 mL | 7.6373 mL | 15.2746 mL |
| 5 mM | 305.5 μL | 1.5275 mL | 3.0549 mL |
| 10 mM | 152.7 μL | 763.7 μL | 1.5275 mL |
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Quality Control & SDS
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- Purity: >98.00%
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Average Rating: 5 (Based on Reviews and 12 reference(s) in Google Scholar.)
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