5.38765

PDI Inhibitor IV, LOC14

• Synonym(e): 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
• Empirische Formel (Hill-System): C₁₆H₁₉N₃O₂S
• Molekulargewicht: 317.41
• UNSPSC-Code: 12352200

Eigenschaften

• Assay: ≥98% (HPLC)
• Qualitätsniveau: 100
• Form: solid
• Hersteller/Markenname: Calbiochem^®
• Lagerbedingungen: OK to freeze; protect from light
• Farbe: white
• Löslichkeit: DMSO: 25 mg/mL
• Lagertemp.: 2-8°C

Beschreibung

Allgemeine Beschreibung

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.

Biochem./physiol. Wirkung

Cell permeable: yes

Primary Target
PDI

Reversible: yes

Verpackung

Packaged under inert gas

Warnhinweis

Toxicity: Standard Handling (A)

Rekonstituierung

Use only anhydrous DMSO for reconstitution.

Sonstige Hinweise

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

Rechtliche Hinweise

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

Sicherheitshinweise

• Lagerklassenschlüssel: 11 - Combustible Solids
• WGK: WGK 3
• Flammpunkt (°F): Not applicable
• Flammpunkt (°C): Not applicable