1. GPCR/G Protein
  2. CaSR
  3. NPS-2143

NPS-2143 (Synonyms: SB 262470A)

Cat. No.: HY-10007 Purity: 99.42%
Handling Instructions

NPS-2143 is a selective antagonist of calcium-sensing receptor (CaSR) with an IC50 of 43 nM.

For research use only. We do not sell to patients.

NPS-2143 Chemical Structure

NPS-2143 Chemical Structure

CAS No. : 284035-33-2

Size Price Stock Quantity
Free Sample (0.5-1 mg)   Apply now  
10 mM * 1 mL in DMSO USD 106 In-stock
Estimated Time of Arrival: December 31
5 mg USD 96 In-stock
Estimated Time of Arrival: December 31
10 mg USD 132 In-stock
Estimated Time of Arrival: December 31
50 mg USD 420 In-stock
Estimated Time of Arrival: December 31
100 mg USD 660 In-stock
Estimated Time of Arrival: December 31
200 mg   Get quote  
500 mg   Get quote  

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Other Forms of NPS-2143:

Top Publications Citing Use of Products

    NPS-2143 purchased from MCE. Usage Cited in: Am J Physiol Heart Circ Physiol. 2010 Nov;299(5):H1309-17.

    Distribution of cardioprotective signaling kinases among fractions prepared from perfusion, IPC, and NPS2143-treated IPC hearts. After nondetergent caveolae fractionation via sucrose gradient ultracentrifugation, equal volume of each collected sucrose fraction is subjected to 4–12% SDS-PAGE under reducing condition and followed with p-ERK1/2 (A), p-AKT (B), and p-GSK-3β (C) IB detection. The representative IBs are taken and shown from one out of three independent experiments.

    NPS-2143 purchased from MCE. Usage Cited in: J Vet Sci. 2018 Mar 31;19(2):179-187.

    The protein levels of calcium-sensing receptor (CaSR) and its signal molecules regulated by CaSR antagonist NPS 2143. The protein images of CaSR, protein kinase C (PKC), and inositol trisphosphate receptor (IP3R) in the presence of 20 mM tryptophan and NPS 2143.

    NPS-2143 purchased from MCE. Usage Cited in: Oxid Med Cell Longev. 2017;2017:3869561.

    N-formyl-Met-Leu-Phe (fMLP; 10 nM) are used to stimulate the cells for 2 min, and the polymorphonuclear neutrophils (PMNs) without fMLP serve as the control. NPS-2143 (100 nM), Cinacalcet (100 nM), and PDTC (100 nM) are added and incubated. Protein expression results are representative of three experiments.
    • Biological Activity

    • Protocol

    • Technical Information

    • Purity & Documentation

    • References

    Description

    NPS-2143 is a selective antagonist of calcium-sensing receptor (CaSR) with an IC50 of 43 nM.

    IC50 & Target

    IC50: 43 nM (Ca2+ receptor)

    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. 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 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

    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 rats. In normotensive rats, NPS-2143 administration (1 mg/kg, i.v.) markedly increases mean arterial blood pressure (MAP) in the presence of parathyroid glands[2].

    Storage
    Powder -20°C 3 years
      4°C 2 years
    In solvent -80°C 6 months
      -20°C 1 month
    Solvent & Solubility
    In Vitro: 

    DMSO : ≥ 100 mg/mL (244.55 mM)

    *"≥" means soluble, but saturation unknown.

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.4455 mL 12.2273 mL 24.4547 mL
    5 mM 0.4891 mL 2.4455 mL 4.8909 mL
    10 mM 0.2445 mL 1.2227 mL 2.4455 mL
    *Please refer to the solubility information to select the appropriate solvent.
    In Vivo:
    • 1.

      Add each solvent one by one:  10% DMSO    40% PEG300    5% Tween-80    45% saline

      Solubility: ≥ 2.5 mg/mL (6.11 mM); Clear solution

    • 2.

      Add each solvent one by one:  10% DMSO    90% corn oil

      Solubility: ≥ 2.5 mg/mL (6.11 mM); Clear solution

    *All of the co-solvents are provided by MCE.
    References
    Kinase Assay
    [1]

    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+]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.

    MCE has not independently confirmed the accuracy of these methods. They are for reference only.

    Animal Administration
    [1]

    Rats: On the day of study, the rats are infused intravenously (0.1 mL/kg·min) for 120 min with NPS-2143 (0.1 μmol/kg·min) or vehicle, a 20% aqueous solution of 2-hydroxypropyl-β-cyclodextrin. Blood samples (0.5 mL) are collected before and at various times after the start of the infusion for measurements of plasma levels of PTH and Ca2+. To prevent excessive blood volume loss during the course of the experiment, for each blood sample the erythrocyte pellet is resuspended in an equal volume of normal rat plasma and reinjected. Plasma levels of Ca2+ are measured immediately after collection using a model 634 ionized calcium analyzer. 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.

    References
    Molecular Weight

    408.92

    Formula

    C₂₄H₂₅ClN₂O₂

    CAS No.

    284035-33-2

    SMILES

    N#CC1=C(OC[[email protected]@H](CNC(C)(CC2=CC=C3C=CC=CC3=C2)C)O)C=CC=C1Cl

    Shipping

    Room temperature in continental US; may vary elsewhere

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    Product Name:
    NPS-2143
    Cat. No.:
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    Cat. No.: HY-10007