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

NPS-2143  (Synonyms: SB-262470A)

Cat. No.: HY-10007 Purity: 99.33%
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NPS-2143 (SB-262470A), an orally active calcilytic agent, is a selective and potent calcium ion-sensing receptor (CaSR) antagonist. NPS-2143 (SB-262470A) blocks increases in cytoplasmic Ca2+ concentrations (IC50=43 nM) elicited by activating the Ca2+ receptor in HEK 293 cells expressing the human Ca2+ receptor.

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

NPS-2143 Chemical Structure

NPS-2143 Chemical Structure

CAS No. : 284035-33-2

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10 mM * 1 mL in DMSO
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Customer Review

Based on 18 publication(s) in Google Scholar

Other Forms of NPS-2143:

NPS-2143 Related Antibodies

Top Publications Citing Use of Products

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

    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 MedChemExpress. Usage Cited in: Oxid Med Cell Longev. 2017;2017:3869561.  [Abstract]

    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.

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

    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.

    • Biological Activity

    • Protocol

    • Purity & Documentation

    • References

    • Customer Review

    Description

    NPS-2143 (SB-262470A), an orally active calcilytic agent, is a selective and potent calcium ion-sensing receptor (CaSR) antagonist. NPS-2143 (SB-262470A) blocks increases in cytoplasmic Ca2+ concentrations (IC50=43 nM) elicited by activating the Ca2+ receptor in HEK 293 cells expressing the human Ca2+ receptor[1][2].

    IC50 & Target

    IC50: 43 nM (Ca2+ receptor)
    In Vitro

    NPS-2143 (SB-262470A) 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].

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

    NPS-2143 Related Antibodies
    In Vivo

    NPS-2143 (SB-262470A) results in a rapid 4- to 5-fold increase in plasma PTH levels in rats[1].
    ? 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].

    MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
    Molecular Weight

    408.92

    Formula

    C24H25ClN2O2
    CAS No.
    Appearance

    Solid

    Color

    White to off-white

    SMILES

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

    Room temperature in continental US; may vary elsewhere.
    Storage
    Powder -20°C 3 years
    4°C 2 years
    In solvent -80°C 2 years
    -20°C 1 year
    Solvent & Solubility
    In Vitro: 

    DMSO : 17.86 mg/mL (43.68 mM; ultrasonic and adjust pH to 2 with HCl; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

    Preparing
    Stock Solutions
    Concentration Solvent Mass 1 mg 5 mg 10 mg
    1 mM 2.4455 mL 12.2273 mL 24.4546 mL
    5 mM 0.4891 mL 2.4455 mL 4.8909 mL
    View the Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

    • Molarity Calculator

    • Dilution Calculator

    Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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    Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

    This equation is commonly abbreviated as: C1V1 = C2V2

    Concentration (start)

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    In Vivo:

    Select the appropriate dissolution method based on your experimental animal and administration route.

    For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
    To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
    The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

    • Protocol 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

      This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.

      Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
    • Protocol 2

      Add each solvent one by one:  10% DMSO    90% Corn Oil

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

      This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

      Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

    In Vivo Dissolution Calculator
    Please enter the basic information of animal experiments:

    Dosage

    mg/kg

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    (per animal)

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    (per animal)

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    Number of animals

    Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
    Please enter your animal formula composition:
    %
    DMSO +
    % 
    +
    %
    Tween-80 +
    %
    Saline
    Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
    The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
    Calculation results:
    Working solution concentration: mg/mL
    Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
    The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
    Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
     If the continuous dosing period exceeds half a month, please choose this protocol carefully.
    Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
    Purity & Documentation

    Purity: 99.33%

    COA (246 KB) HNMR (328 KB) LCMS (268 KB)

    Handling Instructions (2659 KB)
    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

    Complete Stock Solution Preparation Table

    * Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
    Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.

    Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
    DMSO 1 mM 2.4455 mL 12.2273 mL 24.4546 mL 61.1366 mL
    5 mM 0.4891 mL 2.4455 mL 4.8909 mL 12.2273 mL
    10 mM 0.2445 mL 1.2227 mL 2.4455 mL 6.1137 mL
    15 mM 0.1630 mL 0.8152 mL 1.6303 mL 4.0758 mL
    20 mM 0.1223 mL 0.6114 mL 1.2227 mL 3.0568 mL
    25 mM 0.0978 mL 0.4891 mL 0.9782 mL 2.4455 mL
    30 mM 0.0815 mL 0.4076 mL 0.8152 mL 2.0379 mL
    40 mM 0.0611 mL 0.3057 mL 0.6114 mL 1.5284 mL
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    NPS-2143 Related Classifications

    Help & FAQs
    • Do most proteins show cross-species activity?

      Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

    Keywords:

    NPS-2143284035-33-2SB-262470ANPS2143NPS 2143CaSRCalcium-sensing receptorInhibitorinhibitorinhibit

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