NPS-2143 |
| رقم الكتالوجGC16943 |
NPS-2143 (SB-262470A) ، عامل مكلس نشط عن طريق الفم ، هو مضاد انتقائي وفعال لمستقبلات استشعار أيون الكالسيوم (CaSR)
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 284035-33-2
Sample solution is provided at 25 µL, 10mM.
NPS-2143 is a calcification drug that acts as an antagonist of the calcium-sensing receptor (CaSR) and consequently stimulates the release of parathyroid hormone[1].
Treating Cortical nontumorigenic adult human astrocytes(NAHAs) with fAβ25–35 alone significantly increased at 48 h the release of cytokines and chemokines into the conditioned media. However, NPS-2143(100nM) effectively hinders the Secretion of cytokines and chemokines: IL-6, MCP-2, RANTES, and s-ICAM-1 from NAHAs[2].
NPS-2143 significantly reduced cell proliferation with halfmaximal (50%) inhibitory concentration (IC50) values of 4.08 and 5.71 μM in MDA-MB-231 and MCF-7 cells, respectively. NPS-2143 induced caspase 3/7 activation in MDA-MB-231 breastcancer cells which was accompanied with a remarkable reduction in the expression of Bcl-2antiapoptotic protein. NPS-2143 suppressed migratory and invasive abilities of MDA-MB-231cells with a significant reduction in the expression of p-ERK1/2 and integrin β1 proteins.NPS-2143 to suppress proliferative, migratory andinvasive effects of breast cancer cells which was accompanied by caspase 3/7 activation andsuggests the potential of NPS-2143 as a promising anti-cancer molecule in breast cancer[3].
NPS-2143 was administered as a single ip bolus to wild-type and Nuf mice and plasma concentrations of calcium and PTH, and urinary calcium excretion measured. In vitro administration of NPS-2143 rectifying the gain-of-function associated with the Nuf mouse CaSR mutation. Intraperitoneal injection of NPS-2143 in Nuf mice led to significant increases in plasma calcium and PTH without elevating urinary calcium excretion. These studies of a mouse model with an activating CaSR mutation demonstrate NPS-2143 to normalize the gain-of-function causing ADH1 and improve the hypocalcemia associated with this disorder[4].
References:
[1].Wang S, Qiu L, et al. NPS - 2143 (hydrochloride) inhibits melanoma cancer cell proliferation and induces autophagy and apoptosis. Med Sci (Paris). 2018 Oct;34 Focus issue F1:87-93.
[2].Chiarini A, Armato U, et al. CaSR Antagonist (Calcilytic) NPS 2143 Hinders the Release of Neuroinflammatory IL-6, Soluble ICAM-1, RANTES, and MCP-2 from Aβ-Exposed Human Cortical Astrocytes. Cells. 2020 Jun 2;9(6):1386.
[3].Alqudah MAY, Azaizeh M, et al. Calcium-Sensing Receptor Antagonist NPS-2143 Inhibits Breast Cancer cell Proliferation, Migration and Invasion via Downregulation of p-ERK1/2, Bcl-2 and Integrin β1 and Induces Caspase 3/7 Activation. Adv Pharm Bull. 2022 Mar;12(2):383-388.
[4].Hannan FM, Walls GV, et al. The Calcilytic Agent NPS 2143 Rectifies Hypocalcemia in a Mouse Model With an Activating Calcium-Sensing Receptor (CaSR) Mutation: Relevance to Autosomal Dominant Hypocalcemia Type 1 (ADH1). Endocrinology. 2015 Sep;156(9):3114-21.
| Cell experiment [1]: | |
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Cell lines |
breast cancer cell line (MDA-MB-231 and MCF-7 ) |
|
Preparation Method |
The biological effects of various concentrations of NPS-2143 on breast cancer cell proliferation measured by in vitro MTT assay. |
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Reaction Conditions |
0.5-10 µM NPS-2143 for 48 h. |
|
Applications |
The cell viability of both MDA-MB-231 and MCF-7 cells was reduced after NPS-2143 treatment in a dose-dependent manner. 5-10 µM NPS-2143 significantly reduced MCF-7 and MDA-MB-23 cell viability as compared to DMSO-treated controls. |
| Animal experiment [2]: | |
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Animal models |
wild-type, Nuf/+, and Nuf/Nuf mice |
|
Preparation Method |
A single bolus of NPS 2143 or vehicle (15% aqueous solution of 2-hydroxypropyl- β-cyclodextrin) was administered to mice. Plasma samples were obtained at either 0, 1, 4, or 24 hours by tail vein or terminal bleed. |
|
Dosage form |
30 mg/kg, i.p. injection |
|
Applications |
NPS-2143 successfully improved the hypocalcemia associated with Nuf/+ and Nuf/Nuf mice compared with mice given the drug vehicle alone or untreated mice. At 4 hours after NPS 2143 administration, plasma calcium values remained significantly elevated in wild-type and affected Nuf/+ mice compared with respective untreated mice. |
|
References: [1]. Alqudah MAY, Azaizeh M, et al. Calcium-Sensing Receptor Antagonist NPS-2143 Inhibits Breast Cancer cell Proliferation, Migration and Invasion via Downregulation of p-ERK1/2, Bcl-2 and Integrin β1 and Induces Caspase 3/7 Activation. Adv Pharm Bull. 2022 Mar;12(2):383-388. [2]. Hannan FM, Walls GV, et al. The Calcilytic Agent NPS 2143 Rectifies Hypocalcemia in a Mouse Model With an Activating Calcium-Sensing Receptor (CaSR) Mutation: Relevance to Autosomal Dominant Hypocalcemia Type 1 (ADH1). Endocrinology. 2015 Sep;156(9):3114-21. |
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| Cas No. | 284035-33-2 | SDF | |
| Chemical Name | 2-chloro-6-[(2R)-2-hydroxy-3-[(2-methyl-1-naphthalen-2-ylpropan-2-yl)amino]propoxy]benzonitrile | ||
| Canonical SMILES | CC(C)(CC1=CC2=CC=CC=C2C=C1)NCC(COC3=C(C(=CC=C3)Cl)C#N)O | ||
| Formula | C24H25ClN2O2 | M.Wt | 408.93 |
| الذوبان | ≥ 40.9mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4454 mL | 12.227 mL | 24.4541 mL |
| 5 mM | 0.4891 mL | 2.4454 mL | 4.8908 mL |
| 10 mM | 0.2445 mL | 1.2227 mL | 2.4454 mL |
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- Purity: >99.00%
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