General description
A cell-permeable, blood brain barrier permeable, orally bioavailable, non-toxic benzothiazolone derived compound that acts a potent, reversible and non-covalent inhibitor of protein disulfide isomerase (PDI) reductase activity (Kd = 61.7 nM for PDIa). Shown to bind to PDIa stoichiometrically (1:1), adjacent to the active site, and enforce PDI to adopt an oxidized conformation. Dose-dependently rescues both PC12 cells (EC50 = 500 nM) and medium spiny neurons from mutant huntingtin neurotoxicity. Exhibits favorable microsomal (k = 0.0016, t1/2 = 438.7 min, CLint = 0.17 ml/min/g mouse liver) and blood plasma stability (k = 0.0049, t1/2 = 144 min and 49.9% remains after 2 h incubation) and is well tolerated in mice (20 mg/kg, p.o.).
A cell-permeable, blood brain barrier permeable, orally bioavailable, non-toxic benzothiazolone derived compound that acts a potent, reversible and non-covalent inhibitor of protein disulfide isomerase (PDI) reductase activity (Kd = 61.7 nM for PDIa). Shown to bind to PDIa stoichiometrically (1:1), adjacent to the active site, and enforce PDI to adopt an oxidized conformation. Dose-dependently rescues both PC12 cells (EC50 = 500 nM) and medium spiny neurons from mutant huntingtin neurotoxicity. Exhibits favorable microsomal (k = 0.0016, t1/2 = 438.7 min, CLint = 0.17 ml/min/g mouse liver) and blood plasma stability (k = 0.0049, t1/2 = 144 min and 49.9% remains after 2 h incubation) and is well tolerated in mice (20 mg/kg, p.o.).
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
PDI
Reversible: yes
Packaging
Packaged under inert gas
Warning
Toxicity: Standard Handling (A)
Reconstitution
Use only anhydrous DMSO for reconstitution.
Other Notes
Kaplan, A., et al. 2015. Proc. Natl. Acad. Sci. USA112, In press.
Legal Information
CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany
Molecular Weight: 317.41. Empirical Formula: C16H19N3O2S. Assay: ≥. 98% (HPLC). Quality Level: 100. form: solid. manufacturer/tradename: Calbiochem®. . storage condition: OK to freeze, protect from light. color: white. solubility: DMSO: 25 . mg/mL. storage temp.: 2-8°C. Storage Class Code: 11 - Combustible Solids. WGK: WGK 3. Flash Point(F): Not applicable. Flash Point(C): Not applicable.- UPC:
- 51111644
- Condition:
- New
- Weight:
- 1.00 Ounces
- HazmatClass:
- No
- WeightUOM:
- LB
- MPN:
- 5387650001