NPS-2143-SB-262470A-DataSheet-生命科學試劑-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemENPS-2143Cat. No.: HY-10007CAS No.: 284035-33-2Synonyms: SB 262470A分式: CHClNO分量: 408.92作靶點: CaSR作通路: GPCR/G Protein儲存式: Powder -20C 3 years4C 2 yearsIn solvent -80C 6 months-20C 1 month溶解性數(shù)據(jù)體外實驗 DMSO : 100 mg/mL (244.55 mM)* mean

2、s soluble, but saturation unknown.Mass Solvent1 mg 5 mg 10 mg Concentration制備儲備液1 mM 2.4455 mL 12.2273 mL 24.4547 mL5 mM 0.4891 mL 2.4455 mL 4.8909 mL10 mM 0.2445 mL 1.2227 mL 2.4455 mL請根據(jù)產品在不同溶劑中的溶解度，選擇合適的溶劑配制儲備液，并請注意儲備液的保存式和期限。體內實驗 請根據(jù)您的實驗動物和給藥式選擇適當?shù)娜芙獍?，配制前請先配制澄清的儲備液，再依次添加助溶?為保證實驗結果的可靠性，體內實驗的作液，建

3、議您現(xiàn)現(xiàn)配，當天使；澄清的儲備液可以根據(jù)儲存條件，適當保存；以下溶劑前的百分 指該溶劑在您配制終溶液中的體積占)：1. 請依序添加每種溶劑： 10% DMSO 40% PEG300 5% Tween-80 45% salineSolubility: 2.5 mg/mL (6.11 mM); Clear solution2. 請依序添加每種溶劑： 10% DMSO 90% corn oilSolubility: 2.5 mg/mL (6.11 mM); Clear solution1/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEBIOLOGICA

4、L ACTIVITY物活性 NPS-2143是選擇性的鈣敏感受體 (CaSR) 拮抗劑，IC50 為 43 nM。IC50 & Target IC50: 43 nM (Ca2+ receptor)體外研究 NPS-2143 blocks increases in cytoplasmic Ca2+ concentrations with IC50 of 43 nM elicited by activating theCa2+ receptor in HEK 293 cells expressing the human Ca2+ receptor. NPS-2143 stimulates para

5、thyroidhormone (PTH) secretion from bovine parathyroid cells with EC50 of 41 nM. Moreover, NPS 214 also blocksthe inhibitory effects of calcimimetic NPS R-467 on PTH secretion from bovine parathyroid cells and theinhibitory effects of extracellular Ca2+ on isoproterenol-stimulated increases in cycli

6、c AMP formation 1. InHEK-293 cells transiently expressing hCaSRs, NPS-2143 significantly suppresses the kokumi taste byeffectively inhibiting the activity of both GSH and -Glu-Val-Gly 3. A recent study shows that NPS-2143treatment suppresses low molecular weight fractions of azuki hydrolysate-induce

7、d cholecystokinin (CCK)secretion in CaSR-transfected HEK 293 cells 4.體內研究 NPS-2143 results in a rapid 4- to 5-fold increase in plasma PTH levels and also a transient increase inplasma Ca2+ levels 1 in rats. In normotensive rats, NPS-2143 administration (1 mg/kg, i.v.) markedlyincreases mean arterial

8、 blood pressure (MAP) in the presence of parathyroid glands 2.PROTOCOLKinase Assay 1 This clonal cell line, referred to as HEK 293 4.0-7 cells, are used in a high-throughput screening format todetect agonists and allosteric activators of the Ca2+ receptor. Changes in the concentration of cytoplasmic

9、Ca2+i provide a quantitative and functional assessment of Ca2+ receptor activity in these cells and theresults using this assay parallel those obtained using a homologous expression system of bovine parathyroidcells. On-line continuous measurements of fluorescence in fluo-3- or fura-2-loaded HEK 293

10、 4.0-7 cells areobtained 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 1.0mM to 1.75 mM. NPS-2143 is tested individually at a concentration of 100

11、 g/mL (20 M-80 M) and thosecausing more than a 40% inhibition of the control response are considered to be biologically active. Todetermine the potencies (IC50) of NPS-2143 with biological activity, concentration-response curves areobtained and then, as an initial assessment of selectivity, the effe

12、cts of NPS-2143 on Ca2+i evoked by otherG protein-coupled receptors are examined at a concentration several times their IC50. Wild-type HEK 293cells (and HEK 293 4.0-7 cells) express receptors for thrombin, bradykinin, and ATP, which couple to themobilization of intracellular Ca2+. These responses c

13、an be studied to quickly assess any nonselective actionof compounds on G protein-coupled receptors. Additional assays for selectivity include HEK 293 cellsengineered to express receptors most homologous in sequence and topology to the Ca2+ receptor. Theseinclude native or chimeric receptors for vari

14、ous metabotropic glutamate and -aminobutyric acid type Breceptors (GABABRs). Chimeric receptors are created using partial sequences of metabotropic glutamatereceptors and Ca2+ receptors, engineered to couple to activation of phospholipase C and release ofintracellular Ca2+ in HEK 293 cells. NPS-2143

15、 lacking pan-activity are then subjected to structural2/3 Master of Small Molecules 您邊的抑制劑師www.MedChemEmodifications and their potencies and selectivities monitored using these HEK 293 4.0-7 cell assays in aniterative process.MCE has not independently confirmed the accuracy of these methods. They ar

16、e for reference only.Animal Rats: On the day of study, the rats are infused intravenously (0.1 mL/kgmin) for 120 min with NPS-2143 (0.1Administration 1 mol/kgmin) or vehicle, a 20% aqueous solution of 2-hydroxypropyl-cyclodextrin. Blood samples (0.5 mL)are collected before and at various times after

17、 the start of the infusion for measurements of plasma levels ofPTH and Ca2+. To prevent excessive blood volume loss during the course of the experiment, for each bloodsample the erythrocyte pellet is resuspended in an equal volume of normal rat plasma and reinjected.Plasma levels of Ca2+ are measure

18、d immediately after collection using a model 634 ionized calciumanalyzer. PTH levels are measured using the Immutopics rat PTH(1-34) immunoradiometric assay kit.MCE has not independently confirmed the accuracy of these methods. They are for reference only.戶使本產品發(fā)表的科研獻 Oxid Med Cell Longev. 2017;2017:

19、3869561. Am J Physiol Heart Circ Physiol. 2010 Nov;299(5):H1309-17. Gen Comp Endocrinol. 2018 Oct 1;267:1-8. J Food Sci. 2018 Sep;83(9):2394-2401. J Vet Sci. 2018 Mar 31;19(2):179-187.See more customer validations on HYPERLINK / www.MedChemEREFERENCES1. Nemeth EF, et al. Calcilytic compounds: potent and selective Ca2+ receptor antagonists that stimulate secretion of parathyroidhormone. J Pharmacol Exp Ther. 2001 Oct;299(1):323-31.2. Rybczynska A, et al. Hypertensive effect of calcilytic NPS 2143 administration in rats. J Endocrinol. 2006 Oct;191(1):189-95.3. Oh