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NPS-2143 HCl

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Chemical Structure| 324523-20-8 同义名 : SB-262470A hydrochloride;NPS 2143 (hydrochloride);SB-262470A;NPS-2143 hydrochloride
CAS号 : 324523-20-8
货号 : A464000
分子式 : C24H26Cl2N2O2
纯度 : 99%+
分子量 : 445.381
MDL号 : N/A
存储条件：

粉末 Inert atmosphere,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 105 mg/mL(235.75 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

H2O: 1.5 mg/mL(3.37 mM)，配合低频超声，并水浴加热至45℃助溶
动物实验配方：
生物活性
描述 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].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.25mL

0.45mL

0.22mL

11.23mL

2.25mL

1.12mL

22.45mL

4.49mL

2.25mL
参考文献

[1]Nemeth EF, Delmar EG, et al. Calcilytic compounds: potent and selective Ca2+ receptor antagonists that stimulate secretion of parathyroid hormone. J Pharmacol Exp Ther. 2001;299(1):323-31.

[2]Chiarini A, Armato U, et al. Calcium-Sensing Receptor Antagonist NPS 2143 Restores Amyloid Precursor Protein Physiological Non-Amyloidogenic Processing in Aβ-Exposed Adult Human Astrocytes. Sci Rep. 2017;7(1):1277.

[3]Petrel C, Kessler A, et al. Positive and negative allosteric modulators of the Ca2+-sensing receptor interact within overlapping but not identical binding sites in the transmembrane domain. J Biol Chem. 2004;279(18):18990-7.