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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 |
|---|
| CMPD-39
CMPD-39 is a selective USP30 inhibitor with an IC50 of 0.02 μM. CMPD-39 increases protein ubiquitination and accelerates mitophagy. |
| FT709
FT709 is a potent and selective USP9X inhibitor, an IC50 of 82 nM. |
| XL177A
XL177A is a highly potent and selective irreversible USP7 inhibitor with an IC50 of 0.34 nM. |
| LDN-91946
LDN-91946 is a potent, selective and uncompetitive ubiquitin C-terminal hydrolase-L1 (UCH-L1) inhibitor with a Ki app of 2.8 μM. |
| USP5-IN-1
USP5-IN-1, a potent deubiquitinase USP5 inhibitor, binds to the USP5 ZnF-UBD with a KD of 2.8 μM. |
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