There will be a HazMat fee per item when shipping a dangerous goods. The HazMat fee will be charged to your UPS/DHL/FedEx collect account or added to the invoice unless the package is shipped via Ground service. Ship by air in Excepted Quantity (each bottle), which is up to 1g/1mL for class 6.1 packing group I or II, and up to 25g/25ml for all other HazMat items.
Type
HazMat fee for 500 gram (Estimated)
Excepted Quantity
USD 0.00
Limited Quantity
USD 15-60
Inaccessible (Haz class 6.1), Domestic
USD 80+
Inaccessible (Haz class 6.1), International
USD 150+
Accessible (Haz class 3, 4, 5 or 8), Domestic
USD 100+
Accessible (Haz class 3, 4, 5 or 8), International
Aldose reductase, a cytosolic oxidoreductase in the polyol pathway that catalyzes the reduction of a variety of aldehydes and carbonyls, including the reduction of glucose to sorbitol, is important for various organs. Epalrestat is a noncompetitive and reversible aldose reductase inhibitor with IC50 of 72 nM. Epalrestat can reduce sorbitol accumulation both in animals and in humans by attenuating high glucose-mediated neutrophil-endothelial cell adhesion and decreasing the levels of carboxymethyl-lysine. 50 mg oral administration of epalrestat could reach a peak plasma concentration of 3.9 µg/ml only in 1 hr in healthy adults with a protein binding rate of 90.1%. In patients with somatic diabetic neuropathy, the treatment group received epalrestat 50 mg 3 times/day had a significant increase from baseline in MNCV and SNCV as well as the significant difference from baseline in the threshold of vibratory sensation and the higher disappearance rate of spontaneous pain in the upper limbs and lower limbs. In another group, 45 non–insulin-dependent diabetes patients also received 50 mg epalrestat 3 times/day, the results reported significant improvement regarding spontaneous pain, not significant upper extremities and significant VPT in right tibial and radial styloid processes. 28 patients with mild or no symptoms of diabetic neuropathy were treated with 150 mg/day epalrestat, the least F wave latencies and tibial motor nerves were not shortened[1]. In mice plasma, the linearity with a correlation coefficient of 0.9994 was obtained when examined by epalrestat with range of 2-5000 ng/ml and the accuracy and precision were significant in a dose-dependent way with average RSD% values less than 12.3%. Epalrestat could be rapidly absorbed and distributed in many tissues at 10 min after oral administration.[2]
Epalrestat/依帕司他 细胞实验
Cell Line
Concentration
Treated Time
Description
References
SUM159 cells
20 µM
Epalrestat significantly suppressed the migration and invasion of SUM159 cells
J Exp Med. 2017 Apr 3;214(4):1065-1079.
MDA-MB231 cells
20 µM
Epalrestat significantly suppressed the migration and invasion of MDA-MB231 cells
J Exp Med. 2017 Apr 3;214(4):1065-1079.
Rat Schwann cells
10-50 μM
4 hours
To assess the effect of EPS on nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, results showed that 10 and 50μM EPS significantly increased nuclear Nrf2 levels.
Redox Biol. 2013 Nov 19;2:15-21.
Rat Schwann cells
10-50 μM
24 hours
To assess the effect of EPS on intracellular glutathione (GSH) levels, results showed that 10 and 50μM EPS significantly increased intracellular GSH levels.
Redox Biol. 2013 Nov 19;2:15-21.
Healthy control fibroblasts
10 μM
48 hours
To evaluate the effect of Epalrestat on polyol metabolism and glycosylation. Results showed Epalrestat decreased intracellular polyol levels and increased GDP-mannose levels.
Cell Rep Med. 2023 Jun 20;4(6):101056.
PMM2-CDG patient-derived fibroblasts
10 μM
48 hours
To evaluate the effect of Epalrestat on polyol metabolism and glycosylation. Results showed Epalrestat decreased intracellular polyol levels and increased GDP-mannose levels.
Cell Rep Med. 2023 Jun 20;4(6):101056.
Non-small cell lung cancer patient-derived tumor organoids (PDTO)
319.4 ng/mL (1 μmol/L)
6 days
To evaluate the effect of Epalrestat in overcoming chemoresistance to carboplatin/paclitaxel in PDTOs. Results showed Epalrestat significantly enhanced chemosensitivity and inhibited PDTO growth and viability.
Clin Cancer Res. 2024 Sep 3;30(17):3855-3867.
Bovine aortic endothelial cells (BAECs)
50 μM
8 hours
To evaluate the time-dependent effect of EPS on GSH levels. Results showed a significant increase in GSH levels after 8 hours.
Redox Biol. 2015;4:87-96.
Bovine aortic endothelial cells (BAECs)
10, 50, 100 μM
24 hours
To evaluate the effect of EPS on intracellular GSH levels. Results showed that 50 and 100 μM EPS significantly increased intracellular GSH levels by 2.7- and 8.4-fold, respectively.
Redox Biol. 2015;4:87-96.
PLC/PRF-5 cells
200 μM
24 hours
Reduction in glycolytic flux and lactate secretion through AKR1B1 inhibition.
JHEP Rep. 2023 Nov 28;6(2):100974.
HepG2 cells
50 μM
24 hours
Inhibition of AKR1B1 activity, reduction in lactate secretion and lipid deposition, reversal of the Warburg effect.
JHEP Rep. 2023 Nov 28;6(2):100974.
Human RA fibroblast-like synoviocytes (RAFLSs)
15–60 μmol/L
2-hour pretreatment followed by 4-hour LPS stimulation
To evaluate the inhibitory effect of Epalrestat on LPS-induced inflammatory cytokine expression. Results showed Epalrestat concentration-dependently suppressed LPS-mediated p65 phosphorylation and downregulated gene expression of AR, TNF-α, IL-1β, and IL-6 without affecting cell viability.
Int J Biol Sci. 2023 Aug 6;19(13):4082-4102.
Epalrestat/依帕司他 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
DSS-induced colitis model
Intraperitoneal injection
40 mg/kg
Injected on Days 1, 3, 5, and 7 of DSS treatment
Epalrestat significantly potentiated the protective effect of mannose against colitis, reducing weight loss, colon shortening, and histological damage, and decreasing the expression of GRP78, CHOP, and CASP12 in IECs and colonic TNF-α production.
Cell Mol Immunol. 2023 Feb;20(2):119-130.
SCID mice
Breast cancer xenograft model
Intragastric
50 mg/kg/d
Once daily for 4 weeks
Epalrestat significantly suppressed tumor growth and lung metastasis of MDA-MB231 cells
J Exp Med. 2017 Apr 3;214(4):1065-1079.
Zebrafish
Pmm2 mutant zebrafish
Direct addition to embryo media
10 μM or 40 μM
24 hours
To evaluate the effect of Epalrestat on polyol metabolism and glycosylation. Results showed Epalrestat decreased polyol levels and increased GDP-mannose levels.
Cell Rep Med. 2023 Jun 20;4(6):101056.
NSG mice
A549 NSCLC xenograft model
Oral or intraperitoneal injection
10 mg/kg body weight
Twice administration, 40 days duration
To evaluate the in vivo efficacy of Epalrestat in overcoming chemoresistance. Results showed both intraperitoneal and oral Epalrestat significantly inhibited tumor growth, with tumor inhibition directly proportional to intratumoral Epalrestat concentration.
Clin Cancer Res. 2024 Sep 3;30(17):3855-3867.
BALB/c mice
High-fructose diet and DEN-induced MASLD-HCC model
Oral
50 mg/kg/day
Once daily for 21 days
Inhibition of AKR1B1 activity, reversal of high-fructose diet and DEN-induced MASLD-HCC, reduction in hepatic lipid deposition and metabolic markers.
JHEP Rep. 2023 Nov 28;6(2):100974.
Sprague Dawley rats
Adjuvant-induced arthritis (AIA) model
Oral
15.5 mg/kg/day
Once daily for 27 days
To assess the impact of Epalrestat monotherapy on arthritis severity in AIA rats. Results demonstrated Epalrestat significantly exacerbated joint swelling, bone destruction, and inflammatory markers (e.g., Th17 cell proportion and 4-HNE levels), but co-treatment with NAC reversed these effects and enhanced anti-arthritic efficacy.
Int J Biol Sci. 2023 Aug 6;19(13):4082-4102.
Mice
Brachial plexus root avulsion (BPRA) model
Oral gavage
40 mg/kg bodyweight
Once daily for 14 days
Epalrestat is neuroprotective against BPRA injury by increasing autophagy level, alleviating neuroinflammation and rescuing MNs death in mice.
搜索
HazMat Fee +
