Dabrowski Michael A, Dekermendjian Kim, Lund Per-Eric, Krupp Johannes J, Sinclair Jon, Larsson Olof
Department of Molecular Pharmacology, Local Discovery RA CNS & Pain Control, Astrazeneca R&D Södertälje, SE-151 85 Södertälje, Sweden.
CNS Neurol Disord Drug Targets. 2008 Apr;7(2):122-8. doi: 10.2174/187152708784083867.
Ion channels are at present the third biggest target class in drug discovery. Primary research is continually uncovering potential new ion channel targets in indications such as cancer, diabetes and respiratory diseases, as well as the more established fields of pain, cardiovascular disease, and neurological disorders. Despite the physiological significance and therapeutic relevance in a wide variety of biological systems, ion channels still remain under exploited as drug targets. This is to a large extent resulting from the historical lack of screening technologies to provide the throughput and quality of data required to support medicinal chemistry. Although technical challenges still lie ahead, this historic bottleneck in ion channel drug discovery is now being overcome by novel technologies that can be integrated into lead generation stages of ion channel drug discovery to allow the development of novel therapeutic agents. This review describes the variety of technologies available for ion channel screening and discusses the opportunities these technologies provide. The challenges that remain to be addressed are highlighted.
离子通道目前是药物研发中第三大热门靶点类别。前沿研究不断揭示出癌症、糖尿病和呼吸系统疾病等适应症中潜在的新型离子通道靶点，以及疼痛、心血管疾病和神经紊乱等传统领域中的靶点。尽管离子通道在多种生物系统中具有生理意义和治疗相关性，但作为药物靶点，它们仍未得到充分开发。这在很大程度上是由于历史上缺乏能够提供支持药物化学所需数据通量和质量的筛选技术。尽管技术挑战依然存在，但离子通道药物研发中的这一历史瓶颈现在正被新技术所克服，这些新技术可整合到离子通道药物研发的先导化合物发现阶段，从而推动新型治疗药物的开发。本文综述描述了可用于离子通道筛选的各类技术，并讨论了这些技术带来的机遇。同时也强调了仍有待解决的挑战。
