
Customer Validation
- •Haematologica. 2017 Oct;102(10):e415-e418.
- •Eur J Pharmacol. 2017 Jan 15;795:1-7.
Description |
Senicapoc is a potent and selective Gardos channel blocker with IC50 value of 11 nM, and blocks Ca2+-induced rubidium flux from human RBCs with an IC50 value of 11 nM and inhibits RBC dehydration with IC50 of 30 nM. |
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IC50 & Target |
IC50: 11 nM (Gardos channel) |
In Vitro |
ICA-17043 is shown to block the Gardos channel of mouse (C57 Black) RBCs with an IC50 of 50±6 nM. ICA-17043 blocks this increase in cellular hemoglobin concentration in human RBCs in a concentration-dependent fashion[1]. |
In Vivo |
ICA-17043 (10 mg/kg, p.o.) administration produces a significant decrease in Gardos channel activity measured at day 11 and 21 and is associated with a corresponding increase in red cell K+ content without changes in Na+ content. ICA-17043 (10 mg/kg, twice a day) induces a significant increase in Hct after 11 days of dosing in the SAD mouse[1]. Senicapoc (30 mg/kg, p.o.) reduces airway hyperresponsiveness, eosinophil numbers in bronchoalveolar lavage taken 48 hours post-allergen challenge, and vascular remodelling in the sheep[2]. |
Clinical Trial |
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References |
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Preparing Stock Solutions |
Please refer to the solubility information to select the appropriate solvent.
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Cell Assay
[1] |
Senicapoc is dissolved in DMSO or 100% ethanol. The whole blood is initially diluted 1:1 with Modified Flux Buffer (MFB), consisting of 140 mM NaCl, 5 mM KCl, 10 mM Tris (tris(hydroxymethyl)aminomethane), 0.1 mM EGTA (ethyleneglycoltetraacetic acid) (pH=7.4). The blood is centrifuged at 1000 rpm, and the pellet comprised primarily of RBCs is washed 3 times with MFB. The cells are then loaded with 86Rb+ by incubating the washed cells with 86Rb+ at a final concentration of 0.185 MBq/mL (5 μCi/mL) in MFB for at least 3 hours at 37°C. After loading with 86Rb+, the RBCs are washed 3 times with chilled MFB. The cells are then incubated for 10 minutes with test compound (senicapoc) at concentrations that ranged from 1 nM to 10 000 nM. Efflux of 86Rb+ is initiated by raising intracellular calcium levels in the RBCs with the addition of CaCl2 and A23187 (a calcium ionophore) to final concentrations of 2 mM and 5 μM, respectively. After 10 minutes of incubation at room temperature, the RBCs are pelleted in a microcentrifuge, and the supernatant is removed and counted in a Wallac MicroBeta liquid scintillation counter. MCE has not independently confirmed the accuracy of these methods. They are for reference only. |
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Animal Administration
[1] |
Senicapoc is dissolved in a cremophore/PEG-400/water (10:10:80) mixture. Transgenic Hbbsingle/single SAD1 (SAD) female and male mice between 3 and 6 months of age, weighing 25 to 30 g, are used for this study. The SAD mice are divided into 2 groups, and either vehicle (n=6) or senicapoc (10 mg/kg) (n=6) is administered orally by gavage twice daily. C57B6/2J mice are used as controls (wild-type mice). Hematologic parameters are evaluated at baseline and after 11 and 21 days of therapy. Blood sampling and vehicle administration have previously been shown not to affect the blood parameters measured in this study. MCE has not independently confirmed the accuracy of these methods. They are for reference only. |
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References |
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Molecular Weight |
323.34 |
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Formula |
C₂₀H₁₅F₂NO |
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CAS No. |
289656-45-7 |
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Storage |
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Shipping | Room temperature in continental US; may vary elsewhere |
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Solvent & Solubility |
10 mM in DMSO Senicapoc is formulated with 20% 2-Hydroxypropyl-β-cyclodextrin as a suspension[3]. * "<1 mg/ml"="" means="" slightly="" soluble="" or="" insoluble.="" "≥"="" means="" soluble,="" but="" saturation="">1> |
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References |
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Purity: 99.83%
COA (93 KB) HNMR (155 KB) LCMS (113 KB)
Handling Instructions (1252 KB)-
[1]. Stocker JW, et al. ICA-17043, a novel Gardos channel blocker, prevents sickled red blood cell dehydration in vitro and in vivo in SAD mice. Blood. 2003 Mar 15;101(6):2412-8.
[2]. Van Der Velden J, et al. K(Ca)3.1 channel-blockade attenuates airway pathophysiology in a sheep model of chronic asthma. PLoS One. 2013 Jun 24;8(6):e66886.
[3]. Staal RG, et al. Inhibition of the potassium channel KCa3.1 by senicapoc reverses tactile allodynia in rats with peripheral nerve injury. Eur J Pharmacol. 2017 Jan 15;795:1-7.
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求助各位大神,现在想购买小分子数据库,求大神推荐。
我知道的免费的数据库有zinc
求推荐哪家公司或者研究所的小分子数据库可以购买,十分感谢!!!!!!
就是蛋白质分子的小片断
是氨基酸形成的
westblot蛋白免疫印迹实验跑小分子蛋白(15kd)条带一直是波浪状,有人说是胶的问题,可同时跑了36kd蛋白,条带是直的,有人说是要恒流跑,电压不要太大,我的转膜条件是50v,50min,请教各位大神指点,万分感谢!!!
有机的是有机化合物的简称,它指的是含碳化合物.
但是,有四大类常见物质一般不作为有机物处理:
1、碳的氧化物,如CO和CO2.
2、碳酸及其盐,如CaCO3.
3、金属碳化物,如CaC2.
4、拟卤素及其化合物,如(CN)2与KSCN.
水的化学式为H2O,它不含有碳元素,故不是有机物.
但若所描述的水不是化学意义的水,而是自然界存在的天然水,那么,水中会溶有一定量的有机物.
2017年4月26日|Filedunder:制药工业,制药企业,孤儿药,新药研发,制药常识,文献综合|Postedby:路人丙
【新闻事件】:在日前正在举行的美国神经学年会上MitsubishiTanabe公布了其ALS药物Edaravone的一个三期临床试验结果。在标准疗法基础上加入Edaravone显著改善ALS患者综合功能指标ALSFRS-R(-5.0对-7.5),同时也改善运动、呼吸等局部功能。Edaravone已经在韩国日本批准用于ALS,去年10月申请在美国上市,今年6月之前有望批准。
【药源解析】:ALS全称叫“肌肉萎缩性侧面硬化病”,也称LouGehrig氏病,因为30年代美国纽约洋基棒球队著名选手LouGehrig死于这个病。2014年风行一时的冰桶挑战让更多人知道了ALS,但ALS新药发现依然缓慢。美国目前只有riluzole这一个上市药物,能增加~10%的一年生存机会。
ALS的发病机理未知,动物模型十分不可靠,所以这个病的新药开发很难。过去10年大约只有十几个药物进入临床,基本全军覆没。走的最远的是百建艾迪的dexpramipexole,2013年初在三期临床失败。Edaravone号称是游离基清除剂,但分子机理未知。Edaravone最早作为中风药物开发,后来扩展到ALS。第一个三期临床失败,今天公布的是症状较轻患者。这个临床是日本人群,Edaravone并没有在美国IND和开展临床试验,所以如果批准将是比较特殊的情况(和Marathon的DMD药物Emflaza情况类似)。
Edaravone的另一个特殊性质是其分子结构。这个化合物分子十分简单,分子量只有174,可以算作是超小分子药物。现在有几十个分子量小于200的FDA批准药物,这类药物因为官能团数目有限不大可能与任何靶点有较高结合能,所以通常靶点未知。靶点未知又没有可靠动物模型,这类药物发现就更加困难。当然动物模型预测性差不是超小分子药物才面临的难题,多数神经系统药物、甚至现在最火热的肿瘤免疫疗法也面临同样问题。
这种临床前缺乏可靠评价体系的药物可以算是有D无R,这要求厂家冒更大的临床风险。只有潜在回报较大如没有任何标准疗法的罕见病或真正颠覆性药物如免疫疗法才可以适当采用这个模式。这个模式扩大化对厂家的长期生存是个威胁,因为新药的未知因素已经很多、成功率已经很低。没有临床前适当去风险的机会主义不可持续。
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★更多深度解析访问《美中药源》~
https://www.yypharm.com/?p=10664

