LOC14 (orally administered by gavage; 20 mg/kg; once daily; 12-28 weeks) significantly improves motor function, attenuated brain atrophy and extended survival in the N171–82Q HD mice[2]. Animal Model: Male N171–82Q HD mice[2] Dosage: 20 mg/kg Administration: Orally administered by gavage; 20 mg/kg; once daily; 12-28 weeks Result: Improved motor function in HD mice.
In Vitro
LOC14 (0.01-100 μM; 24 hours) exhibits the capacity to inhibit recombinant (r)PDIA3 at an IC50 of approximately 5 μM[3]. Cell Viability Assay[3] Cell Line: MTEC cells Concentration: 0.01 μM; 0.1 μM; 0.5 μM; 1 μM; 5 μM; 10 μM; 100 μM Incubation Time: 24 hours Result: Inhibited recombinant (r)PDIA3 activity.
Kinase Assay
Cell Assay
Animal Administration
References
[1]. Kaplan A, et al. Small molecule-induced oxidation of protein disulfide isomerase is neuroprotective. Proc Natl Acad Sci U S A. 2015 Apr 28;112(17):E2245-52.
[2]. Chamberlain N, et al. Lung epithelial protein disulfide isomerase A3 (PDIA3) plays an important role in influenza infection, inflammation, and airway mechanics. Redox Biol. 2019 Apr;22:101129.
[3]. Zhou X, et al. Small molecule modulator of protein disulfide isomerase attenuates mutant huntingtin toxicity and inhibits endoplasmic reticulum stress in a mouse model of Huntington's disease. Hum Mol Genet. 2018 May 1;27(9):1545-1555.
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