KB-130015
(Synonyms: KB015) 目录号 : GC48432
An antiarrhythmic agent
Cas No.:147030-48-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
KB-130015 is an antiarrhythmic agent and a derivative of amiodarone .1 It inhibits potassium currents induced by acetylcholine or adenosine in isolated guinea pig atrial myocytes (IC50s = 0.82 and 0.57 µM, respectively).2 KB-130015 activates or inhibits the voltage-gated potassium channel human-ether-a-go-go (hERG), also known as Kv11.1, in HEK293 cells in a voltage-dependent manner.3 It activates large-conductance calcium-activated potassium (BKCa) channels in HEK293 cells expressing the BKCa subunit Slo1 (EC50 = 20.2 μM).4 KB-130015 (40 mg/kg) prolongs the duration of electrically stimulated action potentials in guinea pig papillary muscle ex vivo.1 It is also an antagonist of human thyroid hormone receptor α (TRα) and TRβ (IC50s = 2.2 and 4.1 µM, respectively, in reporter assays).
1.Carlsson, B., Singh, B.N., Temciuc, M., et al.Synthesis and preliminary characterization of a novel antiarrhythmic compound (KB130015) with an improved toxicity profile compared with amiodaroneJ. Med. Chem.45(3)623-630(2002) 2.Brandts, B., Borchard, R., Macianskiene, R., et al.Inhibition of G protein-coupled and ATP-sensitive potassium currents by 2-methyl-3-(3,5-diiodo-4-carboxymethoxybenzyl)benzofuran (KB130015), an amiodarone derivativeJ. Pharmacol. Exp. Ther.308(1)134-142(2004) 3.Gessner, G., Macianskiene, R., Starkus, J.G., et al.The amiodarone derivative KB130015 activates hERG1 potassium channels via a novel mechanismEur. J. Pharmacol.632(1-3)52-59(2010) 4.Gessner, G., Heller, R., Hoshi, T., et al.The amiodarone derivative 2-methyl-3-(3,5-diiodo-4-carboxymethoxybenzyl)benzofuran (KB130015) opens large-conductance Ca2+-activated K+ channels and relaxes vascular smooth muscleEur. J. Pharmacol.555(2-3)185-193(2007)
| Cas No. | 147030-48-6 | SDF | |
| 别名 | KB015 | ||
| Canonical SMILES | O=C(COC1=C(C=C(CC2=C(C)OC3=C2C=CC=C3)C=C1I)I)O | ||
| 分子式 | C18H14I2O4 | 分子量 | 548.1 |
| 溶解度 | DMSO: 10 mg/ml,Ethanol: 10 mg/ml | 储存条件 | -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 | 1.8245 mL | 9.1224 mL | 18.2448 mL |
| 5 mM | 0.3649 mL | 1.8245 mL | 3.649 mL |
| 10 mM | 0.1824 mL | 0.9122 mL | 1.8245 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。
Dronedarone: an amiodarone analogue
Expert Opin Investig Drugs 2004 Apr;13(4):415-26.PMID:15102590DOI:10.1517/13543784.13.4.415.
Of the antiarrhythmic drugs in current use, amiodarone is one of the most effective and is associated with a comparatively low risk of drug-induced pro-arrhythmia, probably due to its multiple pharmacological actions on cardiac ion channels and receptors. However, amiodarone is associated with significant extra-cardiac side effects and this has driven development of amiodarone analogues. These analogues include short acting analogues (e.g., AT-2001) with similar acute effects to amiodarone, the thyroid receptor antagonist KB-130015 and dronedarone. Dronedarone, (SR-33589; Sanofi-Synthelabo), is a non-iodinated amiodarone derivative that inhibits Na +, K + and Ca 2+ currents. It is a potent inhibitor of the acetylcholine-activated K + current from atrial and sinoatrial nodal tissue, and inhibits the rapid delayed rectifier more potently than slow and inward rectifier K + currents and inhibits L-type calcium current. Dronedarone is an antagonist at alpha- and beta-adrenoceptors and unlike amiodarone, has little effect at thyroid receptors. Dronedarone is more potent than amiodarone in inhibiting arrhythmias and death in animal models of ischaemia- and reperfusion-induced arrhythmias. In the Dronedarone Atrial Fibrillation Study After Electrical Cardioversion (DAFNE) clinical trial, dronedarone 800 mg/day appeared to be effective and safe for the prevention of atrial fibrillation relapses after cardioversion. The Antiarrhythmic Trial with Dronedarone in Moderate-to-Severe Congestive Heart Failure Evaluating Morbidity Decrease (ANDROMEDA) trial was stopped due to a potential increased risk of death in the dronedarone group. Trials of dronedarone in the maintenance of sinus rhythm in patients with atrial fibrillation and a safety and tolerability study in patients with an implantable cardioverter defibrillator are ongoing. Further experimental and clinical studies are required before we have a definitive answer to whether dronedarone has advantages over amiodarone and other amiodarone analogues.
Effects of metabolites and analogs of amiodarone on alveolar macrophages: structure-activity relationship
Am J Physiol Lung Cell Mol Physiol 2004 Aug;287(2):L438-47.PMID:15075249DOI:10.1152/ajplung.00434.2003.
Amiodarone, an antiarrhythmic drug toxic toward the lung, is metabolized through sequential modifications of the diethylaminoethoxy group to mono-N-desethylamiodarone (MDEA), di-N-desethylamiodarone (DDEA), and amiodarone-EtOH (B2-O-EtOH), whose effects on lung cells are unclear. To clarify this, we exposed rabbit alveolar macrophages to analogs with different modifications of the diethylaminoethoxy group and then searched for biochemical signs of cell damage, formation of vacuoles and inclusion bodies, and interference with the degradation of surfactant protein A, used as a tracer of the endocytic pathway. The substances studied included MDEA, DDEA, and B2-O-EtOH, analogs with different modifications of the diethylaminoethoxy group, fragments of the amiodarone molecule, and the antiarrhythmic agents dronedarone (SR-33589) and KB-130015. We found the following: 1). MDEA, DDEA, and B2-O-EtOH rank in order of decreasing toxicity toward alveolar macrophages, indicating that dealkylation and deamination of the diethylaminoethoxy group represent important mechanisms of detoxification; 2). dronedarone has greater, and KB-130015 has smaller, toxicity than amiodarone toward alveolar macrophages; and 3). the benzofuran moiety, which is toxic to liver cells, is not directly toxic toward alveolar macrophages.