LOC14 is a strong inhibitor of Protein disulfide isomerase (PDI), displaying EC50 and Kd values of 500 nM and 62 nM, respectively. It demonstrates high stability in mouse liver microsomes and blood plasma, exhibits low clearance by microsomes, and has minimal binding to plasma proteins[1]. LOC14 suppresses the activity of PDIA3, leading to a reduction in intramolecular disulfide bonds and the subsequent oligomerization (maturation) of HA within lung epithelial cells. LOC14 demonstrates the ability to inhibit recombinant PDIA3, with an IC50 value around 5 μM when applied at concentrations ranging from 0.01 to 100 μM over a period of 24 hours[3].
LOC14 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Candida albicans GDH2346
100 µM
48 hours
LOC14 inhibited the growth of Candida albicans.
mBio. 2024 May 8;15(5):e0063324.
Candida albicans TFPY2307
100 µM
48 hours
LOC14 inhibited the growth of Candida albicans.
mBio. 2024 May 8;15(5):e0063324.
Candida albicans TFPY412
100 µM
48 hours
LOC14 inhibited the growth of Candida albicans.
mBio. 2024 May 8;15(5):e0063324.
Candida albicans 3153A
100 µM
48 hours
LOC14 inhibited the growth of Candida albicans.
mBio. 2024 May 8;15(5):e0063324.
PC12 cells
4, 1, and 0.25 μg/mL
48 hours
To screen compounds that could rescue PC12 cell viability, LOC14 showed potency with EC50=500 nM
Proc Natl Acad Sci U S A. 2015 Apr 28;112(17):E2245-52.
Primary mouse tracheal epithelial cells (MTECs)
10 μM
24 hours
LOC14 treatment inhibited PDIA3 activity, reduced the number of influenza nucleoprotein (NP) positive cells, indicating that LOC14 can inhibit viral replication.
Redox Biol. 2019 Apr;22:101129.
Candida albicans SC5314
100 µM
48 hours
LOC14 inhibited the growth of Candida albicans with an MIC of 31.3 µM.
mBio. 2024 May 8;15(5):e0063324.
Mouse tracheal epithelial cells (MTECs)
10 μM
1 hour pretreatment, 2 hours post-infection
LOC14 decreased NA oligomerization and activity, reduced viral burden and inflammatory response.
Int J Mol Sci. 2022 Jan 19;23(3):1078.
A549 cells
10 μM
1 hour pretreatment, 2 hours post-infection
LOC14 significantly decreased cell death, NA production, disulfide bonds, and activity, as well as inflammatory response.
Int J Mol Sci. 2022 Jan 19;23(3):1078.
Osteoclast precursor cells (OPCs)
5 μM
24 hours
LOC14 inhibited the expression of osteoclast differentiation-related genes (Traf6, Nfatc1) and function-related genes (Ctsk), and suppressed osteoclast differentiation by interfering with calcium oscillation.
Heliyon. 2024 Jul 27;10(15):e35374.
Bone marrow-derived macrophages (BMMs)
0.3125, 0.625, 1.25, 2.5, 5 μM
24 hours
Assessed cytotoxicity of LOC14 on BMMs, showing no significant toxicity at concentrations ranging from 0.3125 to 10 μM.
Heliyon. 2024 Jul 27;10(15):e35374.
VDR KO mouse corneal fibroblasts (MCF)
20 μM
24 hours
To investigate the effect of LOC14 on 1,25-Vit D3 and 24,25-Vit D3-induced CYP24A1 and CYP27B1 expression. Results showed that LOC14 completely blocked the promoting effects of 1,25-Vit D3 and 24,25-Vit D3 on CYP24A1 and CYP27B1 expression.
Curr Eye Res. 2021 Sep;46(9):1271-1282.
VDR WT mouse corneal fibroblasts (MCF)
20 μM
24 hours
To investigate the effect of LOC14 on 1,25-Vit D3 and 24,25-Vit D3-induced CYP24A1 and CYP27B1 expression. Results showed that LOC14 significantly attenuated the promoting effects of 1,25-Vit D3 and 24,25-Vit D3 on CYP24A1 and CYP27B1 expression.
Curr Eye Res. 2021 Sep;46(9):1271-1282.
Human corneal fibroblasts (HCF)
10 μM
24 hours
To investigate the effect of LOC14 on 1,25-Vit D3 and 24,25-Vit D3-induced CYP24A1 and CYP27B1 expression. Results showed that LOC14 had no significant effect on CYP24A1 and CYP27B1 expression in human corneal fibroblasts.
Curr Eye Res. 2021 Sep;46(9):1271-1282.
STHdhQ111/111 cells
5-40 nM
48 hours
LOC14 significantly protected cells from mHtt-induced ATP level reduction
Hum Mol Genet. 2018 May 1;27(9):1545-1555.
LOC14 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
C57BL/6j mice
Wild-type
Intravenous or oral
20 mg/kg
Single dose
To evaluate the BBB penetration of LOC14, results showed that LOC14 could penetrate the BBB and accumulate in the brain
Proc Natl Acad Sci U S A. 2015 Apr 28;112(17):E2245-52.
C57BL/6NJ mice
Influenza virus infection model
Intraperitoneal injection
50 mg/kg
1 hour before infection, 24 or 48 hours post-infection
LOC14 significantly reduced viral burden, NA activity, and inflammatory response.
Int J Mol Sci. 2022 Jan 19;23(3):1078.
C57BL/6J female mice
Ovariectomy (OVX)-induced osteoporosis model
Intraperitoneal injection
5 mg/kg
Every other day for four weeks
LOC14 alleviated OVX-induced bone loss and partially reversed osteogenic impairment caused by OVX.
Heliyon. 2024 Jul 27;10(15):e35374.
Mice
N171–82Q HD mouse model
Oral
20 mg/kg/day
Once daily, starting from 12 weeks of age until the end of the study
LOC14 significantly improved motor function, attenuated brain atrophy, extended survival, and suppressed ER stress
Hum Mol Genet. 2018 May 1;27(9):1545-1555.
LOC14 动物研究
Animal study
When given orally via gavage at a dose of 20 mg/kg once daily for a period ranging from 12 to 28 weeks, LOC14 markedly enhances motor function, reduces brain atrophy, and prolongs survival in N171–82Q HD mice[2].
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