JMV 449
目录号 : GC17784
JMV 449 是一种强效、长效的神经降压素受体激动剂。
Cas No.:139026-66-7
Sample solution is provided at 25 µL, 10mM.
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JMV 449 is a potent, long-lasting neurotensin receptor agonist[1,2]. JMV 499 inhibits the binding of 125I-neurotensin to newborn mouse brain homogenates (IC50=0.15nm), and contracts isolated guinea-pig ileum preparations(EC50=1.9nM)[3].
JMV 449 induced noticeable dose-dependent insulin releasing actions in BRIN-BD11 beta-cells. In combination with either GIP or GLP-1, JMV 449 augmented(P<0.05) the insulinotropic actions of both hormones, as well as enhancing (P<0.001) insulin secretory activity of both incretin peptides[4]. JMV 449 induced high affinity neurotensin receptor (NTR) gene activation in the human neuroblastoma cell line CHP212[5]. JMV 449 (1M) was found to increase tyrosine hydroxylase protein and mRNA abundance after short- and long-term treatments (5 or 72h) in CHP212 cell[6]
MV 449 (25nmol/kg) inhibited (P<0.05–P<0.001) food intake in overnight fasted lean mice, and enhanced (P<0.01) the appetite suppressing effects of an enzymatically stable GLP-1 mimetic. When injected co-jointly with glucose, JMV 449 evoked glucose lowering actions, but more interestingly significantly augmented (P<0.05) the glucose lowering effects of established long-acting GIP and GLP-1 receptor mimetics[4].JMV 449 induces hypothermia and is able to decrease the infarct size both 24h and 14 days after the onset of permanent focal ischaemia demonstrates its significant neuroprotective potential in mouse model of permanent focal ischaemia[7]
References:
[1]. Dubuc I, Costentin J, et al. JMV 449: a pseudopeptide analogue of neurotensin-(8-13) with highly potent and long-lasting hypothermic and analgesic effects in the mouse. Eur J Pharmacol. 1992;219(2):327-329.
[2]. Craig SL, Gault VA, et al. Comparison of independent and combined effects of the neurotensin receptor agonist, JMV-449, and incretin mimetics on pancreatic islet function, glucose homeostasis and appetite control. Biochim Biophys Acta Gen Subj. 2021;1865(8):129917.
[3]. Lugrin D, Vecchini F, et al. Reduced peptide bond pseudopeptide analogues of neurotensin: binding and biological activities, and in vitro metabolic stability. Eur J Pharmacol. 1991;205(2):191-198.
[4]. Irwin N. Comparison of independent and combined effects of the neurotensin receptor agonist, JMV-449, and incretin mimetics on pancreatic islet function, glucose homeostasis and appetite control. Biochim Biophys Acta Gen Subj. 2021;1865(8):129917.
[5]. Najimi M, Souazé F, et al. Activation of receptor gene transcription is required to maintain cell sensitization after agonist exposure. Study on neurotensin receptor. J Biol Chem. 1998;273(34):21634-21641.
[6]. Najimi M, Hermans E, et al. Transcriptional regulation of the tyrosine hydroxylase gene by neurotensin in human neuroblastoma CHP212 cells. Metab Brain Dis. 2001;16(3-4):165-174.
[7]. Torup L, Borsdal J, et al. Neuroprotective effect of the neurotensin analogue JMV-449 in a mouse model of permanent middle cerebral ischaemia. Neurosci Lett. 2003;351(3):173-176.
JMV 449 是一种强效、长效的神经降压素受体激动剂[1,2]。 JMV 499 抑制125I-神经降压素与新生小鼠脑匀浆的结合（IC50=0.15nm），并收缩离体豚鼠回肠制剂（EC 50=1.9nM)[3].
JMV 449 在 BRIN-BD11 β 细胞中诱导显着的剂量依赖性胰岛素释放作用。结合 GIP 或 GLP-1，JMV 449 增强 (P<0.05) 两种激素的促胰岛素作用，以及增强 (P<0.001) 两种肠促胰岛素肽的胰岛素分泌活性[4]。 JMV 449 在人神经母细胞瘤细胞系 CHP212[5] 中诱导高亲和力神经降压素受体 (NTR) 基因激活。 JMV 449 (1M) 被发现在 CHP212 细胞中短期和长期处理（5 或 72 小时）后增加酪氨酸羟化酶蛋白和 mRNA 丰度[6]
MV 449 (25nmol/kg) 抑制 (P<0.05-P<0.001) 过夜禁食瘦小鼠的食物摄入，并增强 (P<0.01) 酶稳定 GLP-1 模拟物的食欲抑制作用。当与葡萄糖共同注射时，JMV 449 引起降糖作用，但更有趣的是显着增强 (P<0.05) 已建立的长效 GIP 和 GLP-1 受体模拟物的降糖作用[4].JMV 449 诱导低温并能够在永久性局灶性缺血发作后 24 小时和 14 天减少梗塞面积，证明其在永久性局灶性缺血小鼠模型中具有显着的神经保护潜力[7]
| Cell experiment [1]: | |
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Cell lines |
Rodent BRIN-BD11 beta-cells |
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Preparation Method |
Cells were incubated (20 min) with JMV 449 alone (1×10-4-1µM), or in combination with GIP (1×10-4-1µM) or GLP-1 (1×10-4-1µM), as well as combination of all three test peptides. |
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Reaction Conditions |
1×10-4-1µM JMV-449 |
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Applications |
JMV-449 displayed significant (P < 0.05 to P < 0.01) dose-dependent insulin secretory activity at 5.6 mM glucose when compared to control cultures. |
| Animal experiment [1]: | |
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Animal models |
Male C57BL/6 mice, 10 month old |
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Preparation Method |
Cumulative food intake was assessed in overnight fasted (18h) mice following i.p. injection of saline vehicle (0.9% w/v NaCl) or test peptide (JMV 449, (D-Ala2)GIP, and exendin-4), with food intake measured at 30min intervals for 180min. |
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Dosage form |
25nmol/kg |
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Applications |
Following combined administration of 25 nmol/kg (d-Ala2)GIP and JMV-449, together with 2.5 nmol/kg exendin-4, there was a significant reduction (P < 0.01) of food intake at 15 min post-injection when compared to (d-Ala2)GIP plus exendin-4 injection alone. |
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References: |
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| Cas No. | 139026-66-7 | SDF | |
| 化学名 | (R)-2-((2S,3R)-2-((S)-2-((R)-1-((R)-6-amino-2-(((R)-2,6-diaminohexyl)amino)hexanoyl)pyrrolidine-2-carboxamido)-3-(4-hydroxyphenyl)propanamido)-3-methylpentanamido)-4-methylpentanoic acid | ||
| Canonical SMILES | O=C([C@@H](CCCCN)NC[C@@H](CCCCN)N)N1[C@@H](C(N[C@H](C(N[C@H](C(N[C@@H](C(O)=O)CC(C)C)=O)[C@H](C)CC)=O)CC(C=C2)=CC=C2O)=O)CCC1 | ||
| 分子式 | C38H66N8O7 | 分子量 | 746.96 |
| 溶解度 | Soluble to 0.80 mg/ml in Water | 储存条件 | Desiccate 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 | 1.3388 mL | 6.6938 mL | 13.3876 mL |
| 5 mM | 0.2678 mL | 1.3388 mL | 2.6775 mL |
| 10 mM | 0.1339 mL | 0.6694 mL | 1.3388 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。
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Quality Control & SDS
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- Purity: >98.00%
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