New drugs for treatment of atrial fibrillation

治疗心房颤动的新药

• 批准号: 6337525
• 负责人: Antonio E. Lacerda
• 金额: $ 9.99万
• 依托单位: CHANTEST, INC.
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-07 至 2002-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6337525
• 关键词: atrial fibrillation; cardiovascular agents; cell line; combinatorial chemistry; drug design /synthesis /production; drug screening /evaluation; electrophysiology; heart pharmacology; high throughput technology; ion channel blocker; membrane channels

Atrial fibrillation (AF) is the commonest cardiac arrhythmia and in its chronic form affects more than two million patients in the USA. AF is associated with cardiac and non-cardiac diseases. About 10% of cases have no obvious cause (lone AF). Stroke is the commonest complication with a 25% greater risk than control in older age groups. Drugs that block sodium, potassium and calcium channels provide the customary treatment. All of these drugs may have toxic side effects because their ion cannel targets are present in ventricle where block may produce lethal arrhythmias. Our long-term objective is to develop a satisfactory drug for AF. As a first step we have identified a novel target that is limited to human atrium and should therefore be free from the risk of ventricular arrhythmias. The specific aim of this proposal is to discover novel, selective drugs acting on this atrial-delimited target for the treatment of AF. The novel target will be expressed in cell lines for use in high throughput functional screens of small compounds derived from directed and diversity libraries. Confirmed leads will be fully characterized and two to five preclinical drug candidates should be available within two years. PROPOSED COMMERCIAL APPLICATIONS: Atrial fibrillation is a very common disease for which there is no satisfactory treatment. A drug that has high efficacy with little toxicity would have great therapeutic and commercial value.

心房颤动（AF）是最常见的心律失常，在美国，其慢性形式影响着200多万患者。AF与心脏和非心脏疾病相关。大约10%的病例没有明显的原因（孤立性房颤）。中风是最常见的并发症，在老年组中风险比对照组高25%。常规的治疗方法是使用阻断钠、钾和钙通道的药物。所有这些药物都可能有毒副作用，因为它们的离子通道靶点都存在于心室，阻断心室可能产生致命的心律失常。我们的长期目标是开发一种令人满意的AF药物。作为第一步，我们已经确定了一个新的目标，仅限于人类心房，因此应该没有室性心律失常的风险。该提案的具体目的是发现新的，选择性药物作用于心房界定的目标，用于治疗AF。新的目标将在细胞系中表达，用于来自定向和多样性库的小化合物的高通量功能筛选。已确认的先导药物将得到充分表征，两年内应可获得两至五种临床前候选药物。拟议的商业应用：心房颤动是一种非常常见的疾病，目前尚无令人满意的治疗方法。一种疗效高、毒性小的药物将具有很大的治疗和商业价值。

项目成果

Oral vanoxerine prevents reinduction of atrial tachyarrhythmias: preliminary results.

• DOI: 10.1111/j.1540-8167.2011.02098.x
• 发表时间: 2011-11
• 期刊: Journal of cardiovascular electrophysiology
• 影响因子: 2.7
• 作者: Cakulev I;Lacerda AE;Khrestian CM;Ryu K;Brown AM;Waldo AL
• 通讯作者: Waldo AL