General description
A cell-permeable, blood-brain barrier permeable, non-toxic pyrazolone compound that potently blocks mutant Cu/Zn SOD1 cytotoxicity (EC50 = 67 nM in PC12 cells expressing mutant G93A SOD1). Shown to directly interact with 26S proteasome PSMC1 and PSMC4 and the chaperone protein TCP-1 and enhance proteasome activity. Offers neuroprotection against protein aggregation induced toxicity and prolongs the survival of ALS transgenic mice by 13.3% (20 mg/kg, i.p., q.d.) Demonstrates attractive microsomal (T1/2 = 93 & 36 min in human & mouse, respectively) and metabolic stability, aqueous solubility (250 µM) and PK profile in mice. Poorly affects the activities of 68-enzymes & receptors, hERG and Cyp450 isozymes at 10 µM.
Please note that the molecular weight for this compound is batch-specific due to variable water content. Please refer to the vial label or the certificate of analysis for the batch-specific molecular weight. The molecular weight provided represents the baseline molecular weight without water.
Biochem/physiol Actions
Cell permeable: yes
Primary Target
26S proteasome PSMC1 and PSMC4 and the chaperone protein TCP-1
Reversible: yes
Packaging
Packaged under inert gas
Preparation Note
Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 3 months at -20°C.
Other Notes
Tripper, P.C., et al. 2014. ACS Chem. Neurosci.5, 823.
Chen, T., et al. 2012. J. Med. Chem.55, 515.
Legal Information
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
Disclaimer
Toxicity: Standard Handling (A)
| assay | ≥98% (HPLC) |
| Quality Segment | 100 |
| form | solid |
| manufacturer/tradename | Calbiochem® |
| storage condition | OK to freeze,protect from light |
| color | white |
| solubility | DMSO: 50 mg/mL |
| storage temp. | 2-8°C |
| SMILES string | C1=C(C=C(C=C1Cl)Cl)OCC2=CC(=O)NN2 |
