[CAS NO. 877963-94-5] LOC14
PRODUCTS SPECIFICATIONS [877963-94-5]
DESCRIPTION [877963-94-5]
Overview
| MDL | MFCD07849042 |
|---|---|
| Molecular Weight | 317.41 |
| Molecular Formula | C16H19N3O2S |
| SMILES | O=C(C(C=CC=C1)=C1S2)N2CN3CCN(C(C4CC4)=O)CC3 |
Summary
LOC14 is a potent Protein disulfide isomerase ( PDI ) inhibitor with EC 50 and K d values of 500 nM and 62 nM, respectively. LOC14 exhibits high stability in mouse liver microsomes and blood plasma, low intrinsic microsome clearance, and low plasma-protein binding [1] . LOC14 inhibits PDIA3 activity, decreases intramolecular disulfide bonds and subsequent oligomerization (maturation) of HA in lung epithelial cells [3] .
IC50 & Target
Kd: 62 nM (PDI) [1]
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] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
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. |
In Vivo
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] .
MCE has not independently confirmed the accuracy of these methods. They are for reference only.
| 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. |
Appearance
Solid
Shipping
Room temperature in continental US; may vary elsewhere.
Storage
4°C, protect from light
* The compound is unstable in solutions, freshly prepared is recommended.
Solvent & Solubility
DMSO : 50 mg/mL ( 157.52 mM ; ultrasonic and warming and heat to 60°C)
Stock Solutions
| Concentration Solvent Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 3.1505 mL | 15.7525 mL | 31.5050 mL |
| 5 mM | 0.6301 mL | 3.1505 mL | 6.3010 mL |
| 10 mM | 0.3150 mL | 1.5752 mL | 3.1505 mL |
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.