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IU1-47 is a potent and specific USP14 inhibitor with an IC50 of 0.6 μM. IU1-47 inhibits IsoT/USP5 with an IC50 of 20 μM. IU1-47 stimulates tau degradation principally via the ubiquitin-proteasome system. IU1-47 (3 μM, 10 and 30 μM; 48 hours) significantly decreases Tau and phosphotau species Ser-202/Thr-205 levels in murine cortical primary neurons. The level of USP14 itself does not change.
| Cell Experiment | |
|---|---|
| Cell lines | Murine cortical primary neurons (DIV5) isolated from APPSwe/P301L transgenic animals |
| Preparation method | Murine cortical primary neurons (DIV5) isolated from APPSwe/P301L transgenic animals were incubated with the indicated doses of IU1-47 for 48 h, then harvested, and processed as above. Immunoblots developed with IRDye-conjugated secondary antibodies show the level of total tau and of several specific phospho (P)-tau species upon IU1-47 treatment. Phosphoepitopes are indicated in parentheses. The top three blots are from one gel; the bottom four blots are from another gel (left). The USP14 blot shows that no change in USP14 protein level was observed upon IU1-47 treatment. Values in the graphs represent an average of two biological replicates representing cortical neurons from littermates. |
| Concentrations | 3 μM, 10 μM and 30 μM |
| Incubation time | 48 hours |
| Animal Experiment | |
|---|---|
| Animal models | |
| Formulation | |
| Dosages | |
| Administration | |
| Molecular Weight | 330.85 |
| Formula | C19H23ClN2O |
| CAS Number | 670270-31-2 |
| Solubility (25°C) | DMSO 8 mg/mL |
| Storage |
Powder -20°C 3 years ; 4°C 2 years In solvent -80°C 6 months ; -20°C 1 month |
| Related Deubiquitinase Products |
|---|
| P005091
P005091 (P5091) is a potent and selective inhibitor of ubiquitin-specific protease (USP) 7 with IC50 of 4.2 μM. |
| P22077
P22077 is a selective inhibitor of ubiquitin-specific protease (USP) 7 with EC50 of 8.6 μM. P 22077 also inhibits USP47 with an EC50 of 8.74 μM. |
| b-AP15
b-AP15 is a deubiquitinases inhibitor for 19S proteasomes activity of Ub-AMC cleavage with IC50 of 2.1 μM. *The compound is unstable in solutions, freshly prepared is recommended |
| PR-619
PR-619 is a broad-spectrum reversible DUB (deubiquitinating enzyme) inhibitor of USP2, USP4, USP5, USP7 and USP8 with an EC50 of 3-9 μM. PR-619 also induces endoplasmic reticulum stress and endoplasmic reticulum stress-associated apoptosis. |
| LDN-57444
LDN-57444 is a reversible, competitive proteasome inhibitor for Uch-L1 with IC50 of 0.88 μM, 28-fold selectivity over isoform Uch-L3. |
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