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Olcegepant

现货
Catalog No.
A3680
降钙素基因相关肽(CGRP)的非肽受体,具有有效性和选择性。
组合的产品项目
规格价格库存 数量
5mg
¥ 1,980.00
现货
10mg
¥ 3,070.00
现货
50mg
¥ 10,730.00
现货
1g
¥ 87,760.00
Ship with 10-15 days

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Background

Olcegepant Description:IC50: 0.1nM on human brain vessels [1]
Olcegepant is the first potent and selective non-peptide antagonist of the calcitonin gene-related peptide 1 (CGRP1) receptor, a key modulator in neurogenic inflammatory pain. Under development by Boehringer Ingelheim GmbH, olcegepant is an intravenously formulated treatment for acute attacks of migraine.
In vitro: Functional studies with SK-N-MC cells demonstrated that CGRP-induced cAMP production was antagonised by both CGRP- (8-37) and olcegepant with pA2 values of 7.8 and 11.2, respectively. [1].
In vivo: Pre-treatment with olcegepant (900 mg/kg) inhibited the capsaicin-induced expression of Fos throughout the spinal trigeminal nucleus by 57%. In contrast, the expression of phosphorylated extracellular signal-regulated kinase in the trigeminal ganglion was not changed by olcegepant pre-treatment. CGRP receptor inhibition, which has been shown to decrease spinal trigeminal activity, is likely to occur in the central nervous system rather than in the periphery including the trigeminal ganglion. This may be important for future therapeutic interventions with CGRP receptor antagonists in migraine. [2].
Clinical trial: In a phase II clinical trial, olcegepant reduced the severity of headache in 60% of migraine sufferers and met secondary endpoints including headache-free rate and rate of sustained response. Only mild-to-moderate transient adverse events were observed, with no adverse cardiovascular symptoms reported. The compound appears to be an effective anti-migraine medication that is well tolerated and does not display the vasoconstrictive effect that precludes the use of triptans and dihydroergotamine in certain patients [3].
Reference:
[1] Edvinsson L, Alm R, Shaw D, Rutledge RZ, Koblan KS, Longmore J, Kane SA. Effect of the CGRP receptor antagonist BIBN4096BS in human cerebral, coronary and omental arteries and in SK-N-MC cells. Eur J Pharmacol. 2002;434(1-2):49-53.
[2] Sixt ML, Messlinger K, Fischer MJ. Calcitonin gene-related peptide receptor antagonist olcegepant acts in the spinal trigeminal nucleus. Brain. 2009;132(Pt 11):3134-41.
[3] Recober A, Russo AF. Olcegepant, a non-peptide CGRP1 antagonist for migraine treatment. IDrugs. 2007;10(8):566-74.

Chemical Properties

StorageStore at -20°C
M.Wt869.66
Cas No.204697-65-4
FormulaC38H47Br2N9O5
SynonymsBIBN-4096; BIBN-4096BS;BIBN4096BS; BIBN 4096BS
Solubility≥87 mg/mL in DMSO with gentle warming, <2.35 mg/mL in EtOH, <2.48 mg/mL in H2O
Chemical NameN-[(2R)-1-[[(2S)-6-amino-1-oxo-1-(4-pyridin-4-ylpiperazin-1-yl)hexan-2-yl]amino]-3-(3,5-dibromo-4-hydroxyphenyl)-1-oxopropan-2-yl]-4-(2-oxo-1,4-dihydroquinazolin-3-yl)piperidine-1-carboxamide
SDFDownload SDF
Canonical SMILESC1CN(CCC1N2CC3=CC=CC=C3NC2=O)C(=O)NC(CC4=CC(=C(C(=C4)Br)O)Br)C(=O)NC(CCCCN)C(=O)N5CCN(CC5)C6=CC=NC=C6
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

激酶实验 [1]:

结合实验

将1 mL SK-N-MC细胞膜 (25 μg) 置于含10 pM 125I-CGRP和抑制剂的结合缓冲液 [10 mM HEPES,pH 7.4,5 mM MgCl2和0.2%牛血清白蛋白 (BSA)] 中孵育。将其置于室温下孵育3小时后,使用GFB玻璃纤维滤板(已采用0.5%聚乙烯亚胺封闭3小时)进行过滤,终止反应。使用冰冷的测定缓冲液将滤板洗涤3次,然后用空气将其干燥。加入闪烁液 (50 mL),使用TopCount 计算放射活性。使Olcegepant的终浓度为500 pM,测定非特异性结合。采用Cheng-Prusoff方程,通过Prism和Ki进行数据分析。

细胞实验 [1]:

细胞系

SK-N-MC细胞

制备方法

在DMSO中的溶解度大于10 mM。若配制更高浓度的溶液,一般步骤如下:请将试管置于37℃加热10分钟和/或将其置于超声波浴中震荡一段时间。原液于-20℃可放置数月。

反应条件

10分钟

实验结果

在SK-N-MC细胞中,CGRP-(8-37)和Olcegepant均拮抗CGRP诱导的cAMP产生,其pA2值分别为7.8和11.2。

动物实验 [2]:

动物模型

大鼠

给药剂量

900 μg/kg;静脉注射;10分钟

实验结果

Olcegepant (900 μg/kg) 预处理抑制辣椒素诱导的三叉神经脊束核Fos蛋白表达 (57%),但不影响三叉神经节中的磷酸化细胞外信号调节激酶的表达。

其它注意事项

请于室内测试所有化合物的溶解度。虽然化合物的实际溶解度可能与其理论值略有不同,但仍处于实验系统误差的允许范围内。

References:

[1]. Edvinsson L, Alm R, Shaw D, Rutledge RZ, Koblan KS, Longmore J, Kane SA. Effect of the CGRP receptor antagonist BIBN4096BS in human cerebral, coronary and omental arteries and in SK-N-MC cells. Eur J Pharmacol. 2002;434(1-2):49-53.

[2]. Sixt ML, Messlinger K, Fischer MJ. Calcitonin gene-related peptide receptor antagonist olcegepant acts in the spinal trigeminal nucleus. Brain. 2009;132(Pt 11):3134-41.

生物活性

描述 Olcegepant是降钙素基因相关肽1(CGRP 1)的非肽拮抗剂,IC50值为0.03 nM。
靶点 CGRP1          
IC50 0.03 nM          

质量控制

化学结构

Olcegepant

相关生物数据

Olcegepant