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
Calcium-sensing receptor (CaSR) is a G-protein coupled receptor expressed on the surface of parathyroid cells that mediates the secretion of parathyroid hormone (PTH). NPS-2143 hydrochloride is an antagonist for CaSR that inhibits the increase of cytoplasmic Ca2+ level induced by the activation of CaSR in HEK 293 cells expressing human CaSR with an IC50 value of 43 nM. NPS-2143 hydrochloride also stimulated the secretion of PTH from bovine parathyroid cells with an EC50 value of 41 nM[1]. In human astrocytes, incubation of NPS-2143 hydrochloride at 100 nM for 30 min inhibited the endogenous secretion of Aβ42/Aβ42-os. The treatment of NPS-2143 hydrochloride also promoted the translocation of hAPP to the plasma membrane in fAβ25-35± microglial cytokine mixture-exposed astrocytes[2]. Oral administration of NPS-2143 hydrochloride (100 μmol/kg) for 8 weeks led to a sustained elevation of plasma PTH level and a significant increase of bone turnover in osteopenic ovariectomized (OVX) rats. Daily oral administration of NPS-2143 hydrochloride (100 μmol/kg) for 5 weeks together with the treatment of 17β-estradiol increased cancellous bone area in OVX rats compared to their counterparts administered with 17β-estradiol alone[1].
作用机制
NPS-2143 hydrochloride acts as an CaSR antagonist by binding to the cavity of the transmembrane domains of CaSR, thereby inhibiting its activation[3].
NPS-2143 HCl 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Renal carcinoma cells
5 µM
1 hour
Inhibit CaSR, reduce calcium-induced cell migration and proliferation
Mol Cancer. 2014 Feb 28;13:42.
HEK293T cells
30 µM
1 hour
To measure the negative allosteric modulation effect of NPS-2143 on ggCaSR, results showed that NPS-2143 significantly inhibited the activity of ggCaSR.
Sci Adv. 2021 Jun 4;7(23):eabg1483.
HEK293 cells
20 nM and 40 nM
1 hour
NPS-2143 at 20 nM concentration increased the EC50 of Val62 Gα11 mutant cells to 2.97 mM, which was not significantly different from untreated WT cells. At 40 nM concentration, the EC50 of mutant cells increased to 3.48 mM, which was significantly higher than untreated WT cells.
JCI Insight. 2017 Feb 9;2(3):e91103.
Human aortic endothelial cells (HAoECs)
1 µM
1 hour
To verify the role of NPS-2143 in inhibiting γ-EV-mediated CaSR activation, the results showed that NPS-2143 reversed the γ-EV-mediated reduction of VCAM-1 and E-selectin, suggesting that the anti-inflammatory effect of γ-EV might be through CaSR-dependent pathways.
J Agric Food Chem. 2020 Aug 26;68(34):9139-9149.
IPEC-J2 cells
6 µM
1 hour
NPS2143 reversed the enhancement effect of tryptophan on the protein concentrations of ZO-1, occludin, claudin-1, and CaSR, significantly reduced the TEER value, and increased the permeability of FITC-dextran
Front Immunol. 2021 Oct 21;12:748497.
HEK-CASR cells
10, 20, 30 nM
1 hour
To investigate whether allosteric inhibition of the CASR might rectify the gain-of-function effect imposed by the GNA11R6OC mutation, the effect of the NPS 2143 calcilytic compound on CASR signaling was examined in HEK-CASR cells expressing either WT Gα11 or mutant (Cys60) Gα11 proteins. NPS 2143 increased the EC50 of Gα11-Cys60–expressing mutant cells in a dose-dependent manner, shifting the calcium response curve towards WT levels.
JCI Insight. 2017 Feb 9;2(3):e91079.
PC12 cells
25 µM
24 hours
To investigate the protective effect of NPS-2143 on PC12 cells in the oxygen-glucose deprivation/reoxygenation (OGD/R) model. The results showed that NPS-2143 significantly improved cell viability and inhibited the apoptotic rate.
Int J Mol Med. 2021 Jan;47(1):302-314.
Human cortical astrocytes
100 nM
30 minutes
NPS 2143 totally suppressed the oversecretion of IL-6 and remarkably reduced the over-release of other inflammatory agents.
Cells. 2020 Jun 2;9(6):1386.
IPAH-PASMC
10 µM
NPS-2143 significantly inhibited the extracellular Ca2+-mediated increase in [Ca2+]cyt in IPAH-PASMC
Circ Res. 2012 Aug 3;111(4):469-81.
HEK 293 cells
43 nM
Identified a compound that inhibits increases in cytoplasmic Ca2+ levels and further optimized to yield NPS 2143
J Clin Invest. 2000 Jun;105(11):1595-604.
Bovine parathyroid cells
39 nM
NPS 2143 stimulated PTH secretion from bovine parathyroid cells
J Clin Invest. 2000 Jun;105(11):1595-604.
NPS-2143 HCl 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
CaR wild-type and CaR-null mice
Intravenous injection
1 mg/kg
Single dose, gavage performed 30 minutes post-injection
To evaluate the inhibitory effect of NPS 2143 on CaR, results showed that NPS 2143 completely inhibited gastrin secretion.
Proc Natl Acad Sci U S A. 2010 Oct 12;107(41):17791-6
Rats
Middle cerebral artery occlusion/reperfusion (MCAO/R) model
Intraperitoneal injection
10 µmol/kg
Single injection, lasting 24 hours
To investigate the neuroprotective effect of NPS-2143 on MCAO/R model rats. The results showed that NPS-2143 significantly reduced neurological function scores and cerebral infarction volume.
Int J Mol Med. 2021 Jan;47(1):302-314.
Rats
Osteoporosis model (OVX rats)
Oral
100 mmol/kg
Daily for 8 weeks
NPS 2143 caused a sustained increase in plasma PTH levels, provoking a dramatic increase in bone turnover but no net change in bone mineral density
J Clin Invest. 2000 Jun;105(11):1595-604.
Mice
Dsk7 mouse model
Oral gavage
100 μmol/kg
Single dose
NPS-2143 significantly increased plasma PTH concentrations in Dsk7/+ and Dsk7/Dsk7 mice and rectified or improved their hypocalcemia.
JCI Insight. 2017 Feb 9;2(3):e91103.
Mice
GNA11R60C mutant mouse model
Intraperitoneal injection
28 mg/kg
Single injection, observed at 4 and 24 hours
To investigate the therapeutic effect of NPS 2143 on GNA11R60C mutant mice, the results showed that NPS 2143 significantly increased serum calcium and PTH levels, suggesting its potential for treating ADH2.
JCI Insight. 2017 Feb 9;2(3):e91079.
Rats
MCT-induced pulmonary hypertension model
Intraperitoneal injection
4.5 mg/kg/day
Once daily for 10 days
NPS-2143 significantly inhibited the development of MCT-induced pulmonary hypertension and right ventricular hypertrophy
搜索
HazMat Fee +
