IU1 | CAS#314245-33-5 | Usp14 inhibitor

MedKoo Cat#: 407102 | Name: IU1

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

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.

Chemical Structure

IU1

CAS#314245-33-5

Theoretical Analysis

MedKoo Cat#: 407102

Name: IU1

CAS#: 314245-33-5

Chemical Formula: C18H21FN2O

Exact Mass: 300.1638

Molecular Weight: 300.38

Elemental Analysis: C, 71.98; H, 7.05; F, 6.32; N, 9.33; O, 5.33

Price and Availability

Size	Price	Availability	Quantity
5mg	USD 285.00	2 Weeks
50mg	USD 750.00	2 Weeks

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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

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Product Data

Product Data

Instruction

View handling instruction

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	mg/mL	mM
Solubility
	DMF	20.0	66.58
	DMF:PBS (pH 7.2) (1:9)	0.1	0.33
	DMSO	40.6	135.02
	Ethanol	40.0	133.17

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 300.38 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:

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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