NPS-2143

製品コードS2633 バッチS263301

印刷

化学情報

Chemical Structure Synonyms SB262470 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C24H25ClN2O2
分子量 408.92 CAS No. 284035-33-2
Solubility (25°C)* 体外 DMSO 82 mg/mL (200.52 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 NPS-2143 (SB262470) is a novel potent and selective antagonist of Ca(2+) receptor with IC50 of 43 nM.
in vitro NPS 2143 blocks increases in cytoplasmic Ca2+ concentrations with IC50 of 43 nM elicited by activating the Ca2+ receptor in HEK 293 cells expressing the human Ca2+ receptor. [1] NPS 2143 stimulates parathyroid hormone (PTH) secretion from bovine parathyroid cells with EC50 of 41 nM. Moreover, NPS 214 also blocks the inhibitory effects of calcimimetic NPS R-467 on PTH secretion from bovine parathyroid cells and the inhibitory effects of extracellular Ca2+ on isoproterenol-stimulated increases in cyclic AMP formation. [1] In HEK-293 cells transiently expressing hCaSRs, NPS 2143 significantly suppresses the kokumi taste by effectively inhibiting the activity of both GSH (data not shown) and γ-Glu-Val-Gly. [3] A recent study shows that NPS 2143 treatment suppresses low molecular weight fractions of azuki hydrolysate-induced cholecystokinin (CCK) secretion in CaSR-transfected HEK 293 cells. [4]
in vivo In rats, NPS 2143 results in a rapid 4- to 5-fold increase in plasma PTH levels and also a transient increase in plasma Ca2+ levels. [1] In normotensive rats, NPS 2143 administration (1 mg/kg) by i.v. markedly increases mean arterial blood pressure (MAP) in the presence of parathyroid glands. [2]

プロトコル(参考用のみ)

キナーゼアッセイ Assays for Assessing Potency and Selectivity of Compounds on Ca2+ Receptor
This clonal cell line, referred to as HEK 293 4.0-7 cells, are used in a high-throughput screening format to detect agonists and allosteric activators of the Ca2+ receptor. Changes in the concentration of cytoplasmic Ca2+([Ca2+]i) provide a quantitative and functional assessment of Ca2+receptor activity in these cells and the results using this assay parallel those obtained using a homologous expression system of bovine parathyroid cells. On-line continuous measurements of fluorescence in fluo-3- or fura-2-loaded HEK 293 4.0-7 cells are obtained using a custom-built spectrofluorimeter or a fluorescence imaging plate reader instrument. NPS 2143 is incubated with cells for 1 minute before increasing the concentration of extracellular Ca2+ from 1.0 mM to 1.75 mM. NPS 2143 is tested individually at a concentration of 100 μg/ml (20 μM-80 μM) and those causing more than a 40% inhibition of the control response are considered to be biologically active. To determine the potencies (IC50) of NPS 2143 with biological activity, concentration-response curves are obtained and then, as an initial assessment of selectivity, the effects of NPS 2143 on [Ca2+]i evoked by other G protein-coupled receptors are examined at a concentration several times their IC50. Wild-type HEK 293 cells (and HEK 293 4.0-7 cells) express receptors for thrombin, bradykinin, and ATP, which couple to the mobilization of intracellular Ca2+. These responses can be studied to quickly assess any nonselective action of compounds on G protein-coupled receptors. Additional assays for selectivity include HEK 293 cells engineered to express receptors most homologous in sequence and topology to the Ca2+ receptor. These include native or chimeric receptors for various metabotropic glutamate and γ-aminobutyric acid type B receptors (GABABRs). Chimeric receptors are created using partial sequences of metabotropic glutamate receptors and Ca2+ receptors, engineered to couple to activation of phospholipase C and release of intracellular Ca2+ in HEK 293 cells. NPS 2143 lacking pan-activity are then subjected to structural modifications and their potencies and selectivities monitored using these HEK 293 4.0-7 cell assays in an iterative process.
動物実験 動物モデル Chronic indwelling catheters are implanted in the inferior vena cava and in the abdominal aorta of male Sprague-Dawley rats.
投薬量 ≤0.1 μmol/kg · min
投与方法 Administered via i.v.

カスタマーフィードバック

Data from [Data independently produced by J Biol Chem, 2014, 289(42), 28835-45]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

The role of calcium-sensing receptor in ginsenoside Rg1 promoting reendothelialization to inhibit intimal hyperplasia after balloon injury [ Biomed Pharmacother, 2023, 163:114843] PubMed: 37201261
Revitalizing Skin Repair: Unveiling the Healing Power of Livisin, a Natural Peptide Calcium Mimetic [ Toxins (Basel), 2023, 16(1)21] PubMed: 38251238
The role of calcium-sensitive receptor in ovalbumin-induced airway inflammation and hyperresponsiveness in juvenile mice with asthma [ Kaohsiung J Med Sci, 2022, 10.1002/kjm2.12601] PubMed: 36169192
Oat β-glucan ameliorates epidermal barrier disruption by upregulating the expression of CaSR through dectin-1-mediated ERK and p38 signaling pathways [ Int J Biol Macromol, 2021, 185:876-889] PubMed: 34237364
Tryptophan Ameliorates Barrier Integrity and Alleviates the Inflammatory Response to Enterotoxigenic Escherichia coli K88 Through the CaSR/Rac1/PLC-γ1 Signaling Pathway in Porcine Intestinal Epithelial Cells [ Front Immunol, 2021, 12:748497] PubMed: 34745120
Tryptophan improves porcine intestinal epithelial cell restitution through the CaSR/Rac1/PLC-γ1 signaling pathway [ Food Funct, 2021, 10.1039/d1fo01075a] PubMed: 34374393
Sustained calcium ion release from bioceramics promotes CaSR-mediated M2 macrophage polarization for osteoinduction [ J Leukoc Biol, 2021, 110(3):485-496] PubMed: 34184323
Calcium-sensing receptor protects intestinal integrity and alleviates the inflammatory response via the Rac1/PLCγ1 signaling pathway [ Anim Biotechnol, 2021, 1-14] PubMed: 34762003
Effect of calcium-sensing receptor on the migration and proliferation of porcine intestinal epithelial cells [ Anim Biotechnol, 2021, 1-10] PubMed: 34459707
Ginsenoside Rg1 attenuates mechanical stress-induced cardiac injury via calcium sensing receptor-related pathway [ J Ginseng Res, 2021, 45(6):683-694] PubMed: 34764723

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人間や獣医の診断であるか治療的な使用のためにでない。

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