WARNING: This product is for research use only, not for human or veterinary use.
MedKoo CAT#: 407102
CAS#: 314245-33-5
Description: IU1 is a selective USP14 inhibitor. IU1 prevents ventilator-induced lung injury in rats. IU1 inhibits the catalytic activity of proteasome-associated Usp14 in vitro (IC50 < 4 μM). IU1 stimulates proteasome activity and substrate degradation. USP14 removes the ubiquitin chain of I-κB, therefore inducing I-κB degradation and increasing cytokine release.
MedKoo Cat#: 407102
Name: IU1
CAS#: 314245-33-5
Chemical Formula: C18H21FN2O
Exact Mass: 300.1638
Molecular Weight: 300.3774
Elemental Analysis: C, 71.98; H, 7.05; F, 6.32; N, 9.33; O, 5.33
Synonym: IU1; IU-1; IU 1
IUPAC/Chemical Name: 1-(1-(4-fluorophenyl)-2,5-dimethyl-1H-pyrrol-3-yl)-2-(pyrrolidin-1-yl)ethan-1-one
InChi Key: JUWDSDKJBMFLHE-UHFFFAOYSA-N
InChi Code: InChI=1S/C18H21FN2O/c1-13-11-17(18(22)12-20-9-3-4-10-20)14(2)21(13)16-7-5-15(19)6-8-16/h5-8,11H,3-4,9-10,12H2,1-2H3
SMILES Code: CC1=CC(C(CN2CCCC2)=O)=C(C)N1C3=CC=C(F)C=C3
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
| Biological target: | IU1 is a special Usp14 inhibitor with an IC50 of 4-5 μM. |
| In vitro activity: | Firstly, to determine the underlying effect of IU1 (a selective inhibitor of USP14) on the proliferation of cervical cancer cells, this study used the CCK-8 assay. HeLa cells were treated with various concentrations of IU1 (0.1, 0.2, 0.5, 1, 2, 5, 10, 20, 50, 100 μM) for 24 h, or 100 μM of IU1 for 12, 24, 48 h. SiHa cells were treated with 0.1, 0.5, 2, 5, 10, 20, 50, 100 μM IU1 for 24h, or 100 μM of IU1 for 12, 24, 48 h. This study found that IU1 significantly decreased cell proliferation in a time- and dose-dependent manner (Figure 1A-D). Reference: Int J Biol Sci. 2020 Sep 16;16(15):2951-2963. https://pubmed.ncbi.nlm.nih.gov/33061808/ |
| In vivo activity: | This study assessed the protective efficacy of inhibiting or downregulating USP14 in rat and mouse (Usp14axJ) neuronal cultures treated with prostaglandin J2 (PGJ2). IU1 concentrations (HIU1>25μM) reported by others to inhibit USP14 and be protective in non-neuronal cells, reduced PGJ2-induced Ub-protein accumulation in neurons. Reference: Biochim Biophys Acta Mol Basis Dis. 2017 Jun;1863(6):1157-1170. https://pubmed.ncbi.nlm.nih.gov/28372990/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMF | 20.0 | 66.58 | |
| DMF:PBS (pH 7.2) (1:9) | 0.1 | 0.33 | |
| DMSO | 40.56 | 135.02 | |
| Ethanol | 40.0 | 133.17 |
The following data is based on the product molecular weight 300.3774 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | 1. Xu L, Wang J, Yuan X, Yang S, Xu X, Li K, He Y, Wei L, Zhang J, Tian Y. IU1 suppresses proliferation of cervical cancer cells through MDM2 degradation. Int J Biol Sci. 2020 Sep 16;16(15):2951-2963. doi: 10.7150/ijbs.47999. PMID: 33061808; PMCID: PMC7545697. 2. Lv C, Wang S, Lin L, Wang C, Zeng K, Meng Y, Sun G, Wei S, Liu Y, Zhao Y. 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. 3. Kiprowska MJ, Stepanova A, Todaro DR, Galkin A, Haas A, Wilson SM, Figueiredo-Pereira ME. Neurotoxic mechanisms by which the USP14 inhibitor IU1 depletes ubiquitinated proteins and Tau in rat cerebral cortical neurons: Relevance to Alzheimer's disease. Biochim Biophys Acta Mol Basis Dis. 2017 Jun;1863(6):1157-1170. doi: 10.1016/j.bbadis.2017.03.017. Epub 2017 Apr 1. PMID: 28372990; PMCID: PMC5549686. 4. Song Y, Li Z, He T, Qu M, Jiang L, Li W, Shi X, Pan J, Zhang L, Wang Y, Zhang Z, Tang Y, Yang GY. M2 microglia-derived exosomes protect the mouse brain from ischemia-reperfusion injury via exosomal miR-124. Theranostics. 2019 May 4;9(10):2910-2923. doi: 10.7150/thno.30879. PMID: 31244932; PMCID: PMC6568171. |
| In vitro protocol: | 1. Xu L, Wang J, Yuan X, Yang S, Xu X, Li K, He Y, Wei L, Zhang J, Tian Y. IU1 suppresses proliferation of cervical cancer cells through MDM2 degradation. Int J Biol Sci. 2020 Sep 16;16(15):2951-2963. doi: 10.7150/ijbs.47999. PMID: 33061808; PMCID: PMC7545697. 2. Lv C, Wang S, Lin L, Wang C, Zeng K, Meng Y, Sun G, Wei S, Liu Y, Zhao Y. 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. |
| In vivo protocol: | 1. Kiprowska MJ, Stepanova A, Todaro DR, Galkin A, Haas A, Wilson SM, Figueiredo-Pereira ME. Neurotoxic mechanisms by which the USP14 inhibitor IU1 depletes ubiquitinated proteins and Tau in rat cerebral cortical neurons: Relevance to Alzheimer's disease. Biochim Biophys Acta Mol Basis Dis. 2017 Jun;1863(6):1157-1170. doi: 10.1016/j.bbadis.2017.03.017. Epub 2017 Apr 1. PMID: 28372990; PMCID: PMC5549686. 2. Song Y, Li Z, He T, Qu M, Jiang L, Li W, Shi X, Pan J, Zhang L, Wang Y, Zhang Z, Tang Y, Yang GY. M2 microglia-derived exosomes protect the mouse brain from ischemia-reperfusion injury via exosomal miR-124. Theranostics. 2019 May 4;9(10):2910-2923. doi: 10.7150/thno.30879. PMID: 31244932; PMCID: PMC6568171. |
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