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
Sacubitrilat (LBQ657) is characterized by its specific stereochemistry, making it a potent inhibitor (5 nM) of the neutral endopeptidase (NEP) through a comprehensive network of interactions at the enzyme's active site[1].
体内研究
The pharmacokinetic profiles of Sacubitrilat (LBQ657) was assessed following single oral doses of LCZ696 at either 400 or 1200 mg under fasting conditions. Sacubitrilat showed corresponding Tmax values of 2.07 and 3.05 hours. The maximum concentration (Cmax) of Sacubitrilat increases dose-proportionally, whereas Sacubitril and Valsartan show less than proportional increases between the doses[2].
体外研究
Sacubitrilat (LBQ657) is characterized by its specific stereochemistry, making it a potent inhibitor (5 nM) of the neutral endopeptidase (NEP) through a comprehensive network of interactions at the enzyme's active site[1].
Sacubitrilat 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Flp-In 293 cell lines
200 µM
10 minutes
To evaluate the impact of CES1 variant G143E on sacubitril activation, and found that G143E is a loss-of-function variant for sacubitril activation.
Drug Metab Dispos. 2016 Apr;44(4):554-9
Recombinant human CES2
200 µM
10 minutes
To confirm that sacubitril is not a substrate of CES2.
Drug Metab Dispos. 2016 Apr;44(4):554-9
Recombinant human CES1
200 µM
10 minutes
To confirm that sacubitril is a selective CES1 substrate.
Drug Metab Dispos. 2016 Apr;44(4):554-9
Murine ventricular cardiomyocytes
40 µM
15 minutes
To investigate the effects of Sacubitrilat on pro-arrhythmogenic sarcoplasmic reticulum Ca2+ leak in murine ventricular cardiomyocytes, results showed that Sacubitrilat significantly reduced Ca2+ leak.
ESC Heart Fail. 2020 Oct;7(5):2992-3002
Fetal human cardiac fibroblasts
20 µM
16 hours
To evaluate the effect of sacubitrilat in combination with ANP or ADM on collagen expression. Results showed that sacubitrilat combined with ANP reduced Col1a2 expression, while sacubitrilat combined with ADM did not show similar effects.
To evaluate the effect of Sacubitrilat on TGF-β1-induced fibrosis and ferroptosis, results showed that Sacubitrilat significantly inhibited the expression of fibrosis and ferroptosis-related proteins.
MedComm (2020). 2023 Jul 14;4(4):e330
Mouse kidney tubular epithelium cells (TCMK-1)
10 µM
24 hours
To evaluate the effect of Sacubitrilat on TGF-β1-induced fibrotic phenotypes, results showed that Sacubitrilat significantly inhibited the expression of fibrotic proteins.
MedComm (2020). 2023 Jul 14;4(4):e330
Human ventricular cardiomyocytes
40 µM
30 minutes
To investigate the effects of Sacubitrilat on pro-arrhythmogenic sarcoplasmic reticulum Ca2+ leak in human ventricular cardiomyocytes from patients with end-stage heart failure, results showed that Sacubitrilat significantly reduced Ca2+ leak.
ESC Heart Fail. 2020 Oct;7(5):2992-3002
MDA-MB-231 (triple-negative breast cancer cells)
23.02 μg/mL
48 hours
To evaluate the inhibitory effect of Sacubitrilat on the proliferation of triple-negative breast cancer cells, showing an IC50 of 23.02 μg/mL.
Sci Rep. 2023 Jun 19;13(1):9952
SW-480 (colorectal cancer cells)
14.07 μg/mL
48 hours
To evaluate the inhibitory effect of Sacubitrilat on the proliferation of colorectal cancer cells, showing an IC50 of 14.07 μg/mL.
Once daily for 7 days (UUO model) or 14 days (adenine model)
To evaluate the effect of Sacubitrilat on kidney fibrosis, results showed that Sacubitrilat significantly alleviated kidney fibrosis, tubular injury, and inflammatory responses.
MedComm (2020). 2023 Jul 14;4(4):e330
Sprague-Dawley rats
Myocardial infarction model
Oral gavage
68 mg/kg/day
Once daily for 42 days
To evaluate the effects of Sac/Val on regional function and remodeling post-MI. Results showed that Sac/Val reduced left ventricular end-diastolic volume, preserved systolic strain in the proximal zone, and reduced fibrotic deposition and pro-apoptotic signaling.
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