5.38765

PDI Inhibitor IV, LOC14

• Sinônimo(s): PDI Inhibitor IV, LOC14, 2-((4-(Cyclopropanecarbonyl)piperazin-1-yl)methyl)benzo[d]isothiazol-3(2H)-one, 2-((4-(Cyclopropylcarbonyl)-1-piperazinyl)methyl)-1,2-benzothiazol-3(2H)-one, Lead Optimized Compound 14, Protein Disulfide Isomerase Inhibitor IV
• Fórmula empírica (Notação de Hill): C₁₆H₁₉N₃O₂S
• Peso molecular: 317.41
• Código UNSPSC: 12352200

Propriedades

• Ensaio: ≥98% (HPLC)
• Nível de qualidade: 100
• forma: solid
• fabricante/nome comercial: Calbiochem^®
• condição de armazenamento: OK to freeze; protect from light
• cor: white
• solubilidade: DMSO: 25 mg/mL
• temperatura de armazenamento: 2-8°C

Descrição

Descrição geral

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 (K_d = 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, t_1/2 = 438.7 min, CL_int = 0.17 ml/min/g mouse liver) and blood plasma stability (k = 0.0049, t_1/2 = 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 (K_d = 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, t_1/2 = 438.7 min, CL_int = 0.17 ml/min/g mouse liver) and blood plasma stability (k = 0.0049, t_1/2 = 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.

Ações bioquímicas/fisiológicas

Cell permeable: yes

Primary Target
PDI

Reversible: yes

Embalagem

Packaged under inert gas

Advertência

Toxicity: Standard Handling (A)

Reconstituição

Use only anhydrous DMSO for reconstitution.

Outras notas

Kaplan, A., et al. 2015. Proc. Natl. Acad. Sci. USA112, In press.

Informações legais

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

Informações de segurança

• Código de classe de armazenamento: 11 - Combustible Solids
• Classe de risco de água (WGK): WGK 3
• Ponto de fulgor (°F): Not applicable
• Ponto de fulgor (°C): Not applicable