| Targets |
USP14 (IC50 = 0.83 μM)
IU1-248 targets ubiquitin-specific protease 14 (USP14), a deubiquitinating enzyme that is associated with the 19S regulatory particle of the proteasome. USP14 removes ubiquitin chains from proteins that are targeted for degradation, thereby rescuing them from proteasomal breakdown. By inhibiting USP14, IU1-248 prevents this deubiquitination, allowing the proteasome to degrade these proteins more efficiently. |
|---|---|
| ln Vitro |
IU1-248 has a USP14 IC50 value of 0.83 μM, which is similar to IU1-47's(IC50=0.68 μM) and ten times more potent than IU1's (IC50=12.25 μM)[1].
In vitro, IU1-248 is a potent and specific USP14 inhibitor with an IC50 of 0.83 µM, which is 10-fold more potent than IU1 (IC50 = 12.25 µM). Its potency makes it a valuable tool for studying the role of USP14 in protein degradation and cellular homeostasis. |
| ln Vivo |
In vivo, IU1-248 is used to study the role of USP14 in various biological processes and diseases. By modulating protein degradation, it can affect pathways involved in cancer, neurodegeneration, and other diseases.
|
| Enzyme Assay |
The inhibitory activity of IU1-248 is assessed using in vitro deubiquitinase assays. Recombinant USP14 is incubated with a ubiquitinated substrate and varying concentrations of the compound. The deubiquitination reaction is measured, and the IC50 is calculated.
|
| Cell Assay |
The cellular activity of IU1-248 is evaluated in various cell lines. Cells are treated with IU1-248, and its effect on the levels of ubiquitinated proteins and on proteasomal degradation is assessed by Western blot. Its effect on cell viability and signaling pathways is also investigated.
|
| Animal Protocol |
In animal studies, IU1-248 would be administered to rodents to study its effects in models of disease. Its effect on protein degradation, disease progression, and pharmacodynamic markers would be assessed.
|
| ADME/Pharmacokinetics |
IU1-248 is a small molecule (MW 337.42, C20H23N3O2). It is soluble in DMSO. Its pharmacokinetic properties would need to be determined for specific in vivo applications.
|
| Toxicity/Toxicokinetics |
Toxicology data for IU1-248 is limited. As a research compound, its safety profile has not been established in formal toxicology studies. Its use is limited to research applications.
|
| References | |
| Additional Infomation |
IU1-248 (CAS: 2307472-03-1) is a potent and selective USP14 inhibitor that is significantly more potent than its parent compound IU1. It is a valuable research tool for studying the role of USP14 in protein quality control and for validating USP14 as a therapeutic target for cancer and other diseases.
|
| Exact Mass |
337.18
|
|---|---|
| Elemental Analysis |
C, 71.19; H, 6.87; N, 12.45; O, 9.48
|
| CAS # |
2307472-03-1
|
| Related CAS # |
2934.99.9001
|
| PubChem CID |
135393505
|
| Appearance |
Light brown to khaki solid powder
|
| LogP |
2.5
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
25
|
| Complexity |
512
|
| Defined Atom Stereocenter Count |
0
|
| InChi Key |
WFOUOZGIXDMUJU-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C20H23N3O2/c1-14-11-19(20(25)13-22-9-7-18(24)8-10-22)15(2)23(14)17-5-3-16(12-21)4-6-17/h3-6,11,18,24H,7-10,13H2,1-2H3
|
| Chemical Name |
4-[3-[2-(4-hydroxypiperidin-1-yl)acetyl]-2,5-dimethylpyrrol-1-yl]benzonitrile
|
| Synonyms |
IU 1248; IU1248; IU1-248
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO: 67~83.3 mg/mL (198.6~247 mM)
Ethanol: ~8 mg/mL (~23.7 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (6.16 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 20.8 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: ≥ 2.08 mg/mL (6.16 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 20.8 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. (Please use freshly prepared in vivo formulations for optimal results.) |
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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