PDI Inhibitor IV, LOC14

Cell permeable: yes

Primary Target
PDI

Reversible: yes

Toxicity: Standard Handling (A)

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.

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

Packaged under inert gas

Use only anhydrous DMSO for reconstitution.

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