ISO-1
(Synonyms: 4,5-二氢-3-(4-羟基苯基)-5-异恶唑乙酸甲酯,MIF Antagonist) 目录号 : GC17108
ISO-1以剂量依赖的方式抑制MIF互变异构酶活性，IC50约为7µM。
Cas No.:478336-92-4
Sample solution is provided at 25 µL, 10mM.
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ISO-1 inhibited MIF tautomerase activity in a dose-dependent manner with an IC50 of about 7 µM[1].
Treatment of the transfected cells with ISO-1 inhibited the release of arachidonic acid in a dose-dependent manner, the MIF inhibitory activities of ISO-1 and its derivatives were not the result of cell toxicity[1]. In monocytes, ISO-1 caused marked suppression of TLR4-induced proinflammatory cytokine production, and to a lesser extent suppression of TLR2-induced responses[6].
ISO-1 inhibits tumor necrosis factor release from macrophages isolated from LPStreated wild type mice but has no effect on cytokine release from MIFdeficient macrophages[2]. ISO-1 exerts anti-cancer effects on PANC-1 cell proliferation, migration and invasion in vitro, and inhibited PANC-1 cell-induced tumour growth in xenograft mice in vivo[3]. ISO-1 treatment alleviated pathological damage in pancreatic and renal tissues, and reduced the serum levels of amylase, lipase, creatinine, uric acid, IL-6 and TNF-α. ISO-1 also reduced protein expression of NLRP3, ASC, caspase-1 and IL-1β, mRNA expression of MIF, IL-6, TNF-α, IL-1β and IL-18, and the infiltration of MPO-positive neutrophils in kidney tissue[4]. ISO-1 may protect the IBD cells, reduce pathological injuries, and reduce the inflammatory response in SAP rats. Its mechanisms may be via inhibiting the expression of MIF and then blocking the activation of p38-MAPK and NF-κB signaling pathway[5]. ISO-1 remarkably improved the histological findings of APAP-induced liver injury in mice. The increases in serum levels of alanine aminotransferase (ALT), and macrophage inflammatory protein-2 (MIP-2) by APAP were inhibited by ISO-1[7].
References:
[1]. Lubetsky JB, Dios A, et,al.The tautomerase active site of macrophage migration inhibitory factor is a potential target for discovery of novel anti-inflammatory agents. J Biol Chem. 2002 Jul 12;277(28):24976-82. doi: 10.1074/jbc.M203220200. Epub 2002 May 7. PMID: 11997397.
[2]. Al-Abed Y, Dabideen D, et,al. ISO-1 binding to the tautomerase active site of MIF inhibits its pro-inflammatory activity and increases survival in severe sepsis. J Biol Chem. 2005 Nov 4;280(44):36541-4. doi: 10.1074/jbc.C500243200. Epub 2005 Aug 22. PMID: 16115897.
[3]. Cheng B, Wang Q, et,al.MIF inhibitor, ISO-1, attenuates human pancreatic cancer cell proliferation, migration and invasion in vitro, and suppresses xenograft tumour growth in vivo. Sci Rep. 2020 Apr 21;10(1):6741. doi: 10.1038/s41598-020-63778-y. PMID: 32317702; PMCID: PMC7174354.
[4]. Liu Y, Liu Y, et,al. MIF inhibitor ISO-1 alleviates severe acute pancreatitis-associated acute kidney injury by suppressing the NLRP3 inflammasome signaling pathway. Int Immunopharmacol. 2021 Jul;96:107555. doi: 10.1016/j.intimp.2021.107555. Epub 2021 Apr 3. PMID: 33823428.
[5]. Wang B, Zhao K, et,al. Protective Mechanism of MIF Inhibitor ISO-1 on Intrahepatic Bile Duct Cells in Rats with Severe Acute Pancreatitis. Dig Dis Sci. 2021 Oct;66(10):3415-3426. doi: 10.1007/s10620-020-06674-9. Epub 2020 Oct 29. PMID: 33123939.
[6]. West PW, Parker LC, et,al. Differential and cell-type specific regulation of responses to Toll-like receptor agonists by ISO-1. Immunology. 2008 Sep;125(1):101-10. doi: 10.1111/j.1365-2567.2008.02825.x. Epub 2008 Mar 18. PMID: 18355244; PMCID: PMC2526264.
[7]. Ohkawara T, Okubo N, et,al. Protective effect of ISO-1 with inhibition of RIPK3 up-regulation and neutrophilic accumulation on acetaminophen-induced liver injury in mice. Toxicol Lett. 2021 Mar 15;339:51-59. doi: 10.1016/j.toxlet.2020.12.015. Epub 2020 Dec 25. PMID: 33370591.
ISO-1以剂量依赖的方式抑制MIF互变异构酶活性，IC50约为7µM[1]。
转染细胞的ISO-处理1以剂量依赖方式抑制花生四烯酸的释放，ISO-1及其衍生物的MIF抑制活性不是细胞毒性的结果[1]。在单核细胞中，ISO-1 显着抑制 TLR4 诱导的促炎细胞因子产生，并在较小程度上抑制 TLR2 诱导的反应[6]。
ISO-1 抑制从 LPS 处理的野生型小鼠分离出的巨噬细胞释放肿瘤坏死因子，但对 MIF 缺陷型巨噬细胞释放细胞因子没有影响[2]。 ISO-1 在体外对 PANC-1 细胞增殖、迁移和侵袭发挥抗癌作用，在体内抑制 PANC-1 细胞诱导的异种移植小鼠肿瘤生长[3]。 ISO-1 治疗减轻了胰腺和肾脏组织的病理损伤，并降低了淀粉酶、脂肪酶、肌酐、尿酸、IL-6 和 TNF-α 的血清水平；。 ISO-1 还降低了 NLRP3、ASC、caspase-1 和 IL-1β 的蛋白表达；MIF、IL-6、TNF-α 的 mRNA 表达；IL-1β；和 IL-18，以及肾组织中 MPO 阳性中性粒细胞的浸润[4]。 ISO-1 可能保护 IBD 细胞，减少病理损伤，并减少 SAP 大鼠的炎症反应。其机制可能是通过抑制MIF的表达进而阻断p38-MAPK和NF-κB信号通路的激活[5]。 ISO-1 显着改善了 APAP 诱导的小鼠肝损伤的组织学发现。 APAP对血清谷丙转氨酶（ALT）和巨噬细胞炎症蛋白2（MIP-2）水平的升高可被ISO-1[7]抑制。
| Kinase experiment [1]: | |
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Preparation Method |
Activity was determined at room temperature by adding dopachrome methyl ester (0.3 ml) to a cuvette containing 50 nm MIF in 50 mm potassium phosphate buffer, pH 6, 0.5 mm EDTA and measuring the decrease in absorbance from 2 to 20 s at 475 nm spectrophotometrically. The inhibitors were dissolved in Me2SO at various concentrations and added to the cuvette with the MIF prior to the addition of the dopachrome. |
|
Reaction Conditions |
1uM-1000uM ISO-1 |
|
Applications |
ISO-1 inhibited MIF tautomerase activity in a dose-dependent manner with an IC50 of about 7 µM, but the non-hydroxylated phenyl analog (compound 2) was 10-15 times less potent |
| Cell experiment [1]: | |
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Cell lines |
RAW 264.7 macrophages |
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Preparation Method |
Cells were subsequently transfected with FuGENE 6 and pcDNA/GS empty vector or FuGENE 6 and pcDNA/GS/MIF in the absence or presence of vehicle (Me2SO) or inhibitors. After 16 h cell supernatants were collected and14C-labeled arachidonic acid was assessed by scintillation counting. |
|
Reaction Conditions |
1-100uM ISO-1 for 16 h |
|
Applications |
Treatment of the transfected cells with ISO-1 inhibited the release of arachidonic acid in a dose-dependent manner, the MIF inhibitory activities of ISO-1 and its derivatives were not the result of cell toxicity. |
| Animal experiment [2]: | |
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Animal models |
Male Balb/C mice, 8 weeks old |
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Preparation Method |
Endotoxemia was induced by injection of a sublethal dose of LPS. Mice were treated with various concentrations of ISO-1 (3.5-35 mg/kg; intraperitoneally) or vehicle (aqueous 5% dimethyl sulfoxide) 30 min before and 6 h after LPS infusion and then twice daily for 3 days. Animals were monitored for survival for 2 weeks. |
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Dosage form |
ISO-1 (3.5-35 mg/kg; intraperitoneally) for 3 days |
|
Applications |
ISO-1 inhibits tumor necrosis factor release from macrophages isolated from LPStreated wild type mice but has no effect on cytokine release from MIFdeficient macrophages. |
|
References: [1]. Lubetsky JB, Dios A, et,al.The tautomerase active site of macrophage migration inhibitory factor is a potential target for discovery of novel anti-inflammatory agents. J Biol Chem. 2002 Jul 12;277(28):24976-82. doi: 10.1074/jbc.M203220200. Epub 2002 May 7. PMID: 11997397. |
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| Cas No. | 478336-92-4 | SDF | |
| 别名 | 4,5-二氢-3-(4-羟基苯基)-5-异恶唑乙酸甲酯,MIF Antagonist | ||
| 分子式 | C12H13NO4 | 分子量 | 235.24 |
| 溶解度 | DMF: 20 mg/ml,DMF:PBS(pH 7.2)(1:1): 0.5 mg/ml,DMSO: 14 mg/ml,Ethanol: 5 mg/ml | 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 | 4.251 mL | 21.2549 mL | 42.5098 mL |
| 5 mM | 0.8502 mL | 4.251 mL | 8.502 mL |
| 10 mM | 0.4251 mL | 2.1255 mL | 4.251 mL |
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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 | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
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2.
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Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet