| 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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| Targets |
26S proteasome inhibitor I targets the Rpn11 (PSMD14) subunit of 26S proteasome (a deubiquitinating enzyme), with an IC₅₀ value of 0.3 μM (Rpn11 deubiquitinating activity inhibition assay) [1]
26S proteasome inhibitor I inhibits 26S proteasome chymotrypsin-like activity with an IC₅₀ value of 0.8 μM (fluorogenic peptide substrate assay) [1] |
|---|---|
| ln Vitro |
26S proteasome inhibitor I (0.1–5 μM) dose-dependently inhibited Rpn11-mediated deubiquitination of ubiquitin-conjugated substrates, achieving 90% inhibition at 2 μM (in vitro deubiquitination assay) [1]
- The compound suppressed 26S proteasome-mediated protein degradation in HeLa cell lysates: 1 μM reduced degradation of ubiquitinated β-catenin by 65% (Western blot) [1] - In human cancer cell lines (HCT116, HeLa, A549): 26S proteasome inhibitor I (0.5–10 μM) dose-dependently inhibited cell proliferation, with IC₅₀ values of 1.2 μM (HCT116), 1.5 μM (HeLa), and 2.0 μM (A549) (MTT assay) [1] - It induced apoptosis in HCT116 cells: 2 μM increased apoptotic rate by 58% (Annexin V-FITC/PI staining), upregulated cleaved caspase-3/caspase-9 by 2.8/3.2-fold, and accumulated p53 protein by 4.5-fold (Western blot) [1] - No significant cytotoxicity was observed in normal human foreskin fibroblasts (NHF) at concentrations up to 10 μM [1] |
| Enzyme Assay |
Rpn11 deubiquitinating activity assay: Recombinant human Rpn11 protein was incubated with ubiquitin-AMC (fluorescent substrate) and serial dilutions of 26S proteasome inhibitor I (0.01–10 μM) in reaction buffer at 37°C for 60 minutes. Fluorescence intensity (excitation 360 nm, emission 460 nm) was measured to quantify free AMC release, and IC₅₀ was calculated based on inhibition rate [1]
- 26S proteasome chymotrypsin-like activity assay: Purified 26S proteasome was mixed with Suc-LLVY-AMC (fluorogenic peptide substrate) and 26S proteasome inhibitor I (0.05–10 μM) at 37°C for 90 minutes. Fluorescence was detected to assess peptide hydrolysis, and IC₅₀ was determined [1] |
| Cell Assay |
Cancer cell proliferation assay: HCT116/HeLa/A549 cells were seeded in 96-well plates (5×10³ cells/well), cultured for 24 hours, and treated with 26S proteasome inhibitor I (0.5–10 μM) for 72 hours. MTT reagent was added, and absorbance at 570 nm was measured to calculate cell viability [1]
- Apoptosis and protein expression assay: HCT116 cells were seeded in 6-well plates, treated with 26S proteasome inhibitor I (0.5–4 μM) for 48 hours. Cells were stained with Annexin V-FITC/PI for apoptosis detection; cell lysates were analyzed by Western blot to detect cleaved caspases, p53, and ubiquitinated proteins [1] - Proteasome activity in cell lysates: HeLa cells were lysed, and supernatants were incubated with 26S proteasome inhibitor I (0.1–5 μM) and ubiquitinated β-catenin substrate. After 3 hours at 37°C, Western blot was performed to detect residual β-catenin levels [1] |
| References | |
| Additional Infomation |
26S proteasome inhibitor I is a synthetic small molecule inhibitor that targets the deubiquitinated subunit Rpn11 of the 26S proteasome [1]. Its mechanism of action includes blocking Rpn11-mediated deubiquitination, inhibiting 26S proteasome-dependent protein degradation, leading to the accumulation of misfolded/ubiquitinated proteins, and inducing apoptosis in cancer cells [1]. This compound has been developed as a potential anticancer drug with much higher selectivity for cancer cells than for normal cells [1]. Unlike classic proteasome inhibitors (such as bortezomib), it specifically targets Rpn11, providing a new strategy for proteasome-targeted therapy [1].
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| Molecular Formula |
C23H25N3O4
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|---|---|
| Molecular Weight |
407.462305784225
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| Exact Mass |
407.18
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| Elemental Analysis |
C, 67.80; H, 6.18; N, 10.31; O, 15.71
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| CAS # |
858557-69-4
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| PubChem CID |
3526723
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| Appearance |
White to off-white solid powder
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| LogP |
3.8
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
30
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| Complexity |
549
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=CC=C(C=C1)C2=NOC(=N2)C3CCN(CC3)C(=O)C4=C(C=CC=C4OC)OC
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| InChi Key |
MPMGADZKWJDRRX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H25N3O4/c1-15-7-9-16(10-8-15)21-24-22(30-25-21)17-11-13-26(14-12-17)23(27)20-18(28-2)5-4-6-19(20)29-3/h4-10,17H,11-14H2,1-3H3
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| Chemical Name |
(2,6-dimethoxyphenyl)-[4-[3-(4-methylphenyl)-1,2,4-oxadiazol-5-yl]piperidin-1-yl]methanone
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| Synonyms |
MUN57694; MUN-57694; MUN 57694;
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| 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) |
DMSO : ~31.25 mg/mL (~76.69 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (5.10 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 (5.10 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. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (5.10 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 | 2.4542 mL | 12.2711 mL | 24.5423 mL | |
| 5 mM | 0.4908 mL | 2.4542 mL | 4.9085 mL | |
| 10 mM | 0.2454 mL | 1.2271 mL | 2.4542 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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