IU1 (Synonyms: Usp14 inhibitor) |
| رقم الكتالوجGC14797 |
IU1 is a cytopermeable, reversible selective inhibitor of proteasome with an IC50 of 4.7μM for USP14.
Products are for research use only. Not for human use. We do not sell to patients.
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.
| 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 | |
| المرادفات | Usp14 inhibitor | ||
| Chemical Name | 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 | ||
| Formula | C18H21FN2O | M.Wt | 300.37 |
| الذوبان | ≥ 10.9 mg/mL in DMSO, ≥ 81.8 mg/mL in EtOH | Storage | Store at 4°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. |
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| 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 | 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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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