Ac-YVAD-CMK
(Synonyms: Caspase-1 Inhibitor II) 目录号 : GC42721
Ac-YVAD-CMK 是一种选择性不可逆的 caspase-1 抑制剂 (Ki=0.8nM)，可阻止促炎细胞因子 IL-1β 的激活。
Cas No.:178603-78-6
Sample solution is provided at 25 µL, 10mM.
Ac-YVAD-CMK is a selective irreversible inhibitor of caspase-1 (Ki=0.8nM), which can prevent the proinflammatory cytokine IL-1β activation. Ac-YVAD-CMK can reduce the inflammatory response and induce a long-lasting neuroprotective effect[1,2,3].
Ac-YVAD-CMK reduced the expression of IL-1β and IL-18 in activated microglia in vitro[3]. Ac-YVAD-CMK(40μM) decreased the rapid cell (PAMs, 3D4/21 cells and the endothelial cell line) death induced by ApxⅠ[4]. Ac-YVAD-CMK attenuated the inhibitory effects of berberine on the viability, migration and invasion of HepG2 cells[5].
AC-YVAD-CMK treatment significantly alleviated sepsis-induced acute kidney injury, with decreased histological injury in renal tissues, suppressed the accumulation of neutrophils and macrophages in renal tissues, and decreased sCR and BUN level[6]. Ac-YVAD-CMK protected the brain against ICH-induced injury, and the neuroprotective effect may result from anti-inflammation-induced blood–brain barrier protection[7]. Pretreatment of rats with Ac-YVAD-CMK (12.5mM/kg) significantly reduced endotoxin-induced mortality from 83% to 33% using Log Rank analysis[8].
References:
[1] Wang F, Li G, et al. Alcohol accumulation promotes esophagitis via pyroptosis activation. Int J Biol Sci. 2018;14(10):1245-1255. Published 2018 Jul 13.
[2] Rabuffetti M, Sciorati C, et al. Inhibition of caspase-1-like activity by Ac-Tyr-Val-Ala-Asp-chloromethyl ketone induces long-lasting neuroprotection in cerebral ischemia through apoptosis reduction and decrease of proinflammatory cytokines. J Neurosci. 2000;20(12):4398-4404.
[3] Liang H, Sun Y, et al. Ac-YVAD-cmk improves neurological function by inhibiting caspase-1-mediated inflammatory response in the intracerebral hemorrhage of rats. Int Immunopharmacol. 2019;75:105771.
[4] Hernandez-Cuellar E, Guerrero-Barrera AL, et al. An in vitro study of ApxI from Actinobacillus pleuropneumoniae serotype 10 and induction of NLRP3 inflammasome-dependent cell death. Vet Rec Open. 2021;8(1):e20. Published 2021 Oct 4.
[5] Chu Q, Jiang Y, et al. Pyroptosis is involved in the pathogenesis of human hepatocellular carcinoma. Oncotarget. 2016;7(51):84658-84665.
[6] Yang M, Fang JT, et al. Caspase-1-Inhibitor AC-YVAD-CMK Inhibits Pyroptosis and Ameliorates Acute Kidney Injury in a Model of Sepsis. Biomed Res Int. 2021;2021:6636621.
[7] Wu B, Ma Q, et al. Ac-YVAD-CMK Decreases Blood-Brain Barrier Degradation by Inhibiting Caspase-1 Activation of Interleukin-1β in Intracerebral Hemorrhage Mouse Model. Transl Stroke Res. 2010;1(1):57-64.
[8] Mathiak G, Grass G, et al. Caspase-1-inhibitor ac-YVAD-cmk reduces LPS-lethality in rats without affecting haematology or cytokine responses. Br J Pharmacol. 2000;131(3):383-386.
Ac-YVAD-CMK 是一种选择性不可逆的 caspase-1 抑制剂 (Ki=0.8nM)，可阻止促炎细胞因子 IL-1β 的激活。 Ac-YVAD-CMK 可降低炎症反应并诱导持久的神经保护作用[1,2,3]。
Ac-YVAD-CMK 在体外降低活化小胶质细胞中 IL-1β 和 IL-18 的表达[3]。 Ac-YVAD-CMK(40μM)降低ApxⅠ诱导的快速细胞(PAMs、3D4/21细胞和内皮细胞系)死亡[4]。 Ac-YVAD-CMK减弱小檗碱对HepG2细胞活力、迁移和侵袭的抑制作用[5]。
AC-YVAD-CMK 治疗显着减轻脓毒症引起的急性肾损伤，减少肾组织的组织学损伤，抑制肾组织中中性粒细胞和巨噬细胞的积累，降低 sCR 和 BUN 水平[6]< /sup>。 Ac-YVAD-CMK 保护大脑免受 ICH 诱导的损伤，神经保护作用可能来自抗炎诱导的血脑屏障保护[7]。使用对数秩分析[8]，用 Ac-YVAD-CMK (12.5mM/kg) 预处理大鼠可将内毒素诱导的死亡率从 83% 显着降低至 33%。
| Cell experiment [1]: | |
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Cell lines |
Microglia cells |
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Preparation Method |
Microglia cells (1×105) were stimulated with the caspase-1 inhibitor Ac-YVAD-CMK (dissolved by DMSO) for 1h. Thrombin was added at a final concentration of 10U/mL to activate the microglia cells for 24h. |
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Reaction Conditions |
40μmol/L or 80μmol/L |
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Applications |
High level Ac-YVAD-CMK treatment (40μmol/L or 80μmol/L) significantly decreased the mRNA levels of IL-1β/IL-18. The 40μmol/L dose of Ac-YVAD-CMK significantly reduced the protein levels of caspase-1 (p20) and mature IL-1β/IL-18 compared with the thrombin-activated microglia group. |
| Animal experiment [2]: | |
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Animal models |
Male Sprague Dawley rats，weighing 250-275g |
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Preparation Method |
Ac-YVAD-CMK (300ng/rat in 3mL) was injected intracerebroventricularly 10 min after permanent middle cerebral artery occlusion in the rat. |
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Dosage form |
300ng/rat in 3mL, intracerebroventricular injection |
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Applications |
Ac-YVAD-CMK treatment induced a significant reduction of infarct volume not only 24 h after ischemia but also 6d later. Ac-YVAD-CMK treatment resulted in a reduction not only of caspase-1 but also of caspase-3 activity at 24h and led to a parallel decrease of apoptosis as measured by nucleosome quantitation. Likewise, brain levels of the proinflammatory cytokines IL-1b and TNF-a were reduced at 24h. |
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References: [1]. Liang H, Sun Y, et al. Ac-YVAD-cmk improves neurological function by inhibiting caspase-1-mediated inflammatory response in the intracerebral hemorrhage of rats. Int Immunopharmacol. 2019;75:105771. [2]. Rabuffetti M, Sciorati C, et al. Inhibition of caspase-1-like activity by Ac-Tyr-Val-Ala-Asp-chloromethyl ketone induces long-lasting neuroprotection in cerebral ischemia through apoptosis reduction and decrease of proinflammatory cytokines. J Neurosci. 2000;20(12):4398-4404. |
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| Cas No. | 178603-78-6 | SDF | |
| 别名 | Caspase-1 Inhibitor II | ||
| 化学名 | N-acetyl-L-tyrosyl-L-valyl-N-[(1S)-1-(carboxymethyl)-3-chloro-2-oxo-propyl]-L-alaninamide | ||
| Canonical SMILES | ClCC(=O)[C@H](CC(=O)O)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@@H](NC(=O)C)Cc1ccc(O)cc1)C(C)C | ||
| 分子式 | C24H33ClN4O8 | 分子量 | 541 |
| 溶解度 | 20mg/mL in DMSO, 10mg/mL in DMF | 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 | 1.8484 mL | 9.2421 mL | 18.4843 mL |
| 5 mM | 0.3697 mL | 1.8484 mL | 3.6969 mL |
| 10 mM | 0.1848 mL | 0.9242 mL | 1.8484 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。
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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