IU1

Description

Biological Activity

Protocol(Only for Reference)

Clinical Trial Information( data from http://clinicaltrials.gov)

Chemical Information

Kinase Assay: [1]

Cell Assay: [1]

References

Name: IU1
Brand: Selleckchem
SKU: S7134

貨號 Cat. No.: S7134
規格 Size: 10mgã€50mg
品牌 Brand: Selleckchem

IU1

Catalog No.S71341 Product Citations

IU1 is a cell-permeable, reversible and selective proteasome inhibitor of human USP14 with IC50 of 4.7 μ M, 25-fold selective to IsoT.

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10mg	USD 185	In stock	0 1 2 3 4 5 6 7 8 9 10
50mg	USD 718	In stock	0 1 2 3 4 5 6 7 8 9 10

Distributor Tel: +886-2-2827-1197jimmy@new.abscience.com.tw

High-throughput screening

Screening is conducted at the ICCB-Longwood screening facility. 10 μL of recombinant USP14 protein are dispensed into each well of a 384-well low volume plate in duplicate, using a Wellmate plate dispenser. 33.3 nL of compound from the library are pin-transferred into the wells using a Seiko pin transfer robotic system, followed by pre-incubation for about 30 min. The last two columns of each plate are used for positive and negative controls for the assay. To initiate the enzyme reaction, 10 μL of VS-proteasome plus Ub-AMC mixture are added to each well, using a Wellmate dispenser. Samples are then incubated for another 45 min. Ub-AMC hydrolysis is measured at Ex355/Em460 using an Envision plate reader. The final concentrations of USP14, VS-proteasome and Ub-AMC are 15 nM, 1 nM and 0.8 μM, respectively. The final concentration of test compound is approximately 17 μM. Enzymes and substrates are prepared in Ub-AMC assay buffer (50 mM Tris-HCl (pH 7.5), 1 mM EDTA, 1 mM ATP, 5 mM MgCl2, 1 mM DTT, and 1 mg/Ml ovalbumin).

Cell lines	MEF cells
Concentrations	~1.5 mM
Incubation Time	48 hours
Method	MTT

NCT Number	Recruitment	Conditions	Sponsor /Collaborators	Start Date	Phases
NCT01198132	Recruiting	Multiple Sclerosis	Merck KGaA\|Merck Serono S.A.S, France	2010-01	Phase 2
NCT01354704	Recruiting	Deep Vein Thrombosis\|Enoxaparin\|Anticoagulants	Les Laboratoires des Médicaments Stériles\|Hospital Charles Nicolle Tunis.	2011-03	Phase 4
NCT01578473	Recruiting	Peyronie’s Disease	Men’s Health Boston	2012-04	Phase 1
NCT01784029	Recruiting	Vitamin D Deficiency	Montefiore Medical Center	2013-01	Phase 4
NCT01774812	Recruiting	Cardiovascular Disease\|Sudden Cardiac Death	University of Calgary\|Alberta Innovates Health Solutions	2013-01	Phase 2

Description

IU1 is a cell-permeable, reversible and selective proteasome inhibitor of human USP14 with IC50 of 4.7 μ M, 25-fold selective to IsoT.

In vitro

IU1 binds specifically to the activated form of USP14. IU1 can potentially inhibit USP14 by preventing its docking on the proteasome, exhibiting little or no activity toward 8 other DUBs, IsoT, UCH37, BAP1, UCH-L1, UCH-L3, USP15, USP2, USP7. USP14 inhibition is rapidly established upon addition of IU1 and rapidly reversed upon its removal. IU1 inhibits USP14 induced chain trimming and decreases electrophoretic mobility of Ub-CCNB species. IU1 enhances proteasomal degradation of Ub-CCNB in the presence of USP14. IU1 promots degradation of tau and depletes TDP-43, ATXN3, and glial fibrillary acidic protein (GFAP) in proteotoxic mechanisms. [1]

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Molecular Weight (MW)	300.37
Formula	C18H21FN2O
CAS No.	314245-33-5

Storage	3 years -20â„ƒPowder
Storage	6 months-80â„ƒin DMSO
Syonnyms	N/A

Solubility (25°C) *	In vitro	DMSO	60 mg/mL (199 mM)
		Water	<1 mg/mL (<1 mM)
		Ethanol	60 mg/mL (199 mM)
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.