IU1
(Synonyms: Usp14 inhibitor) 目录号 : GC14797
IU1是一种细胞可渗透的、可逆的选择性蛋白酶体抑制剂，对USP14的 IC50 为 4.7μM。
Cas No.:314245-33-5
Sample solution is provided at 25 µL, 10mM.
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IU1 is a cytopermeable, reversible selective inhibitor of proteasome with an IC50 of 4.7μM for USP14. IU1 inhibits USP14 by binding to the catalytic cleft in USP14 thus blocking its enzyme activity. Treatment of cultured cells with IU1 enhanced degradation of several proteasome substrates that have been implicated in neurodegenerative disease [1-2].
IU1(25μM) treatment could alleviate endothelial cell leakage induced by OGD in cultured Bend.3 cells through modulating ZO-1 expression[3]. Inhibition of USP14 activity by IU1(100μM; 8h) can significantly reduce the viability of gastric cancer cells MKN74 and inhibit their migration and invasion ability[4]. IU1(1-100μM; 24h) caused a significant decrease in cell proliferation and migration of ML1 cells in a dose dependent manner[5].
IU1(400μg/kg; i.p; 3 times) promotes recovery by protecting the integrity of the blood-brain barrier and alleviating neuroinflammation in MCAO mice by inhibiting USP14[3]. USP14 depletion by IU1(p.o; 40mg/kg/d; 14 days) suppresses Hepatocellular carcinoma (HCC) cell growth in mice[6]. IU1(400μg/kg; i.p; 7days) treatment attenuated ischemic stroke-caused neuronal injury, which was reflected by increased survival rate, reduced infarct volume, as well as decreased neuronal loss in the IU1-treated mice[7].
References:
[1]. Lee BH, Lee MJ, et,al. Enhancement of proteasome activity by a small-molecule inhibitor of USP14. Nature. 2010 Sep 9;467(7312):179-84. doi: 10.1038/nature09299. PMID: 20829789; PMCID: PMC2939003.
[2]. Abramson HN. The Multiple Myeloma Drug Pipeline-2018: A Review of Small Molecules and Their Therapeutic Targets. Clin Lymphoma Myeloma Leuk. 2018 Sep;18(9):611-627. doi: 10.1016/j.clml.2018.06.015. Epub 2018 Jun 18. PMID: 30001985.
[3]. Hou W, Yao J, et,al. USP14 inhibition promotes recovery by protecting BBB integrity and attenuating neuroinflammation in MCAO mice. CNS Neurosci Ther. 2023 Nov;29(11):3612-3623. doi: 10.1111/cns.14292. Epub 2023 Jun 2. PMID: 37269080; PMCID: PMC10580339.
[4]. Lee MY, Kim MJ, et,al.USP14 inhibition regulates tumorigenesis by inducing apoptosis in gastric cancer. BMB Rep. 2023 Aug;56(8):451-456. doi: 10.5483/BMBRep.2023-0063. PMID: 37401238; PMCID: PMC10471464.
[5]. Srinivasan V, Asghar MY, et,al. Proliferation and migration of ML1 follicular thyroid cancer cells are inhibited by IU1 targeting USP14: role of proteasome and autophagy flux. Front Cell Dev Biol. 2023 Aug 30;11:1234204. doi: 10.3389/fcell.2023.1234204. PMID: 37711852; PMCID: PMC10499180.
[6]. Lv C, Wang S, et,al. USP14 maintains HIF1-α stabilization via its deubiquitination activity in hepatocellular carcinoma. Cell Death Dis. 2021 Aug 21;12(9):803. doi: 10.1038/s41419-021-04089-6. PMID: 34420039; PMCID: PMC8380251.
[7].Min JW, Lü L, et,al. USP14 inhibitor attenuates cerebral ischemia/reperfusion-induced neuronal injury in mice. J Neurochem. 2017 Mar;140(5):826-833. doi: 10.1111/jnc.13941. Epub 2017 Jan 26. PMID: 28029679; PMCID: PMC5527549.
IU1是一种细胞可渗透的、可逆的选择性蛋白酶体抑制剂，对USP14的 IC50 为 4.7μM。IU1通过结合USP14的催化裂口抑制USP14，从而阻断其酶活性。用IU1处理细胞可增强与神经退行性疾病有关的几种蛋白酶体底物的降解[1-2]。
IU1(25μM)处理通过调节ZO-1表达，可以缓解OGD（缺氧/复氧损伤）在培养的Bend.3细胞中诱导的内皮细胞渗漏[3]。通过IU1(100μM; 8h)抑制USP14活性可以显著降低胃癌细胞MKN74的活力，并抑制其迁移和侵袭能力[4] 。此外，IU1(1-100μM; 24h)以剂量依赖的方式显著减少了ML1细胞的增殖和迁移能力[5] 。
IU1(400μg/kg; i.p; 3 times)通过抑制USP14，在MCAO（大脑中动脉闭塞）小鼠中保护血脑屏障完整性并减轻神经炎症，从而促进康复[3]。IU1(p.o; 40mg/kg/d; 14 days)耗竭USP14能抑制小鼠肝细胞癌（HCC）细胞的生长[6]。IU1 (400μg/kg; i.p; 7days)处理能减轻缺血性中风引起的神经元损伤，这体现在IU1处理组小鼠生存率提高、梗死体积减少以及神经元丢失减少上[7]。
| Cell experiment [1]: | |
Cell lines | Bend.3 cells |
Preparation Method | Cells were seeded on the top chamber of transwell inserts. After exposing to OGD and IU1 treatment, 300μg/mL FITC-dextran was added to the top chamber. Fifteen minutes later, samples were collected from the bottom chamber for further analysis. |
Reaction Conditions | 25μM |
Applications | IU1 treatment could alleviate endothelial cell leakage induced by oxygen glucose deprivation(OGD) in cultured bend.3 cells through modulating Zonula occludens 1 (ZO-1) expression. |
| Animal experiment [1]: | |
Animal models | Male adult ICR mice model of middle cerebral artery occlusion (MCAO) |
Preparation Method | 400μg/kg body weight IU1 was intraperitoneally injected. The first dose of IU1 was intraperitoneally injected right after MCAO reperfusion, and other two doses were given 24 and 48h post ischemic stroke respectively. |
Dosage form | 400μg/kg; i.p; 3 times |
Applications | IU1 protected Blood-brain barrier (BBB) integrity and reduced leakage after MCAO. |
References: | |
| Cas No. | 314245-33-5 | SDF | |
| 别名 | Usp14 inhibitor | ||
| 化学名 | 1-[1-(4-fluorophenyl)-2,5-dimethylpyrrol-3-yl]-2-pyrrolidin-1-ylethanone | ||
| Canonical SMILES | CC1=CC(=C(N1C2=CC=C(C=C2)F)C)C(=O)CN3CCCC3 | ||
| 分子式 | C18H21FN2O | 分子量 | 300.37 |
| 溶解度 | ≥ 10.9 mg/mL in DMSO, ≥ 81.8 mg/mL in EtOH | 储存条件 | Store at 4°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 | 3.3292 mL | 16.6461 mL | 33.2923 mL |
| 5 mM | 0.6658 mL | 3.3292 mL | 6.6585 mL |
| 10 mM | 0.3329 mL | 1.6646 mL | 3.3292 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%
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