NPS-2143
(Synonyms: 2-氯-6-[(2R)-3-[[1,1-二甲基-2-(2-萘基)乙基]氨基]-2-羟基丙氧基]苯腈,SB-262470A) 目录号 : GC16943
NPS-2143 是一种钙化药物，可作为钙敏感受体 (CaSR) 的拮抗剂，从而刺激甲状旁腺激素的释放。
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.
NPS-2143 是一种钙化药物，可作为钙敏感受体 (CaSR) 的拮抗剂，从而刺激甲状旁腺激素的释放[1]。
单独使用 fAβ25-35 处理皮层非致瘤性成人星形胶质细胞 (NAHA)，在 48 小时后，细胞因子和趋化因子释放到条件培养基中会显着增加。然而，NPS-2143(100nM) 可有效抑制细胞因子和趋化因子的分泌:IL-6、MCP-2、RANTES 和 s-ICAM-1 来自 NAHAs[2]。
NPS-2143 在 MDA-MB-231 和 MCF-7 细胞中显着降低细胞增殖，半数最大 (50%) 抑制浓度 (IC50) 值分别为 4.08 和 5.71 μM。 NPS-2143 在 MDA-MB-231 乳腺癌细胞中诱导 caspase 3/7 激活，同时 Bcl-2 抗凋亡蛋白的表达显着降低。 NPS-2143 抑制 MDA-MB-231 细胞的迁移和侵袭能力，显着降低 p-ERK1/2 和整合素 β1 蛋白的表达。NPS-2143 抑制乳腺癌细胞的增殖、迁移和侵袭作用，并伴有caspase 3/7 激活表明 NPS-2143 具有作为乳腺癌抗癌分子的潜力[3]。
NPS-2143 作为单次腹腔推注给药于野生型和 Nuf 小鼠，并测量钙和 PTH 的血浆浓度，并测量尿钙排泄。 NPS-2143 的体外给药纠正了与 Nuf 小鼠 CaSR 突变相关的功能获得。在 Nuf 小鼠中腹膜内注射 NPS-2143 可导致血浆钙和 PTH 显着增加，而不会增加尿钙排泄。这些对具有激活 CaSR 突变的小鼠模型的研究表明，NPS-2143 可使引起 ADH1 的功能获得正常化并改善与该疾病相关的低钙血症[4]。
| Cell experiment [1]: | |
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Cell lines |
breast cancer cell line (MDA-MB-231 and MCF-7 ) |
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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. |
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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 |
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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. |
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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 | |
| 别名 | 2-氯-6-[(2R)-3-[[1,1-二甲基-2-(2-萘基)乙基]氨基]-2-羟基丙氧基]苯腈,SB-262470A | ||
| 化学名 | 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 | ||
| 分子式 | C24H25ClN2O2 | 分子量 | 408.93 |
| 溶解度 | ≥ 40.9mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
