| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
| Targets |
USP14(IC50= 0.6μM);IsoT/USP5(IC50= 20 μM)
IU1-47 targets USP14, a deubiquitinating enzyme associated with the proteasome. By inhibiting USP14, it enhances the degradation of proteasome substrates. It also inhibits IsoT/USP5 with an IC50 of 20 μM. |
|---|---|
| ln Vitro |
With free USP14 (USP14 that is not attached to the proteasome), IU1-47 is essentially inactive. In vitro, IU1-47 (25 μM) promotes substrate degradation and opposes USP14's deubiquitinating activity.Tau degradation is primarily stimulated by IU1-47 through the ubiquitin-proteasome system. In primary neurons of the murine cortex, IU1-47 (3 μM, 10 and 30 μM; 48 hours) dramatically reduces the levels of Tau and phosphotau species Ser-202/Thr-205. The USP14 level remains constant [1].
IU1-47 inhibits USP14 with an IC50 of 0.6 μM. It causes tau elimination in cultured neurons. It enhances the degradation of proteasome substrates. It decreases migration of and increases autophagy in A549 and H1299 cancer cells. |
| ln Vivo |
In vivo, IU1-47 is used to study the role of USP14 in disease. It has been shown to reduce tau levels in primary rat cortical neurons. Its ability to enhance protein degradation, including pathological tau forms, makes it a potential therapeutic for neurodegenerative diseases.
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| Enzyme Assay |
The primary assay for USP14 inhibition is a biochemical assay using purified USP14 enzyme and a fluorogenic substrate. The enzyme's ability to cleave the substrate is measured in the presence of the compound. IU1-47's potency is determined by its IC50 of 0.6 μM.
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| Cell Assay |
In vitro cellular assays for IU1-47 involve treating cells with the compound and measuring its effect on proteasome activity and the levels of specific substrate proteins. This includes measuring tau protein levels in neuronal cultures and assessing effects on cancer cell migration and autophagy.
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| Animal Protocol |
In vivo animal models for IU1-47 are not detailed in the provided sources. However, its ability to reduce tau in cultured neurons suggests it could be studied in mouse models of tauopathy or Alzheimer's disease. Its effects on cancer progression could also be evaluated in xenograft models.
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| ADME/Pharmacokinetics |
Detailed pharmacokinetic data for IU1-47 is not provided. It is a small molecule with a molecular weight of 378.43 g/mol. It is used as a research tool in biochemical and cellular assays. Its properties for in vivo use are likely being characterized.
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| Toxicity/Toxicokinetics |
Toxicological data for IU1-47 is not detailed. As a research compound, it is not intended for human use. Standard safety precautions should be followed. Its safety profile would need to be established for therapeutic development.
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| References | |
| Additional Infomation |
IU1-47 is a potent and specific USP14 inhibitor, a valuable tool for studying the ubiquitin-proteasome system. Its ability to enhance the degradation of tau protein is of particular interest for neurodegenerative disease research. It is a widely used chemical probe.
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| Molecular Formula |
C19H23CLN2O
|
|---|---|
| Molecular Weight |
330.851723909378
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| Exact Mass |
330.15
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| Elemental Analysis |
C, 68.98; H, 7.01; Cl, 10.71; N, 8.47; O, 4.84
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| CAS # |
670270-31-2
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| PubChem CID |
675477
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| Appearance |
White to off-white solid powder
|
| LogP |
4.3
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
23
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| Complexity |
402
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| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC1=CC(=C(N1C2=CC=C(C=C2)Cl)C)C(=O)CN3CCCCC3
|
| InChi Key |
VXQIPRWKLACSKZ-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C19H23ClN2O/c1-14-12-18(19(23)13-21-10-4-3-5-11-21)15(2)22(14)17-8-6-16(20)7-9-17/h6-9,12H,3-5,10-11,13H2,1-2H3
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| Chemical Name |
1-(1-(4-Chlorophenyl)-2,5-dimethyl-1H-pyrrol-3-yl)-2-(piperidin-1-yl)ethanone
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| Synonyms |
IU1-47; IU1 47; IU147;
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| HS Tariff Code |
2934.99.03.00
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
Ethanol : ~33 mg/mL
DMSO : 8~16.67 mg/mL ( 24.18~50.39 mM ) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.67 mg/mL (5.05 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 1.67 mg/mL (5.05 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 16.7 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 1.67 mg/mL (5.05 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.0225 mL | 15.1126 mL | 30.2252 mL | |
| 5 mM | 0.6045 mL | 3.0225 mL | 6.0450 mL | |
| 10 mM | 0.3023 mL | 1.5113 mL | 3.0225 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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