Trends in ion channel drug discovery: advances in screening technologies

被引:38
作者
Bennett, PB [1 ]
Guthrie, HRE
机构
[1] Merck Res Labs, Dept Mol Pharmacol, West Point, PA 19486 USA
[2] Hoffmann La Roche Inc, Dept Discovery Technol, Nutley, NJ 07110 USA
关键词
D O I
10.1016/j.tibtech.2003.09.014
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
Ion channels mediate and regulate crucial electrical functions throughout the body. They are therapeutic drug targets for a variety of disorders and, in some cases, the direct cause of unwanted side-effects. Advances in medical genetics have increased our knowledge of ion channel structure-function relationships and identified disease-causing mutations in ion channel genes. The recognized importance of these proteins in health and disease has led to an active search for ion channel targets in the multi-billion-dollar worldwide drug discovery market. Trends in ion channel screening technologies have focused on increasing throughput and enhancing information content of assays through electrophysiological approaches. The ability to study ion channels by voltage clamp and their time-, voltage- and state-dependent drug interactions with enhanced throughput will ultimately play a key role in the development of novel, safe ion channel-targeted drugs.
引用
收藏
页码:563 / 569
页数:7
相关论文
共 67 条
[1]   The long QT syndrome: Ion channel diseases of the heart [J].
Ackerman, MJ .
MAYO CLINIC PROCEEDINGS, 1998, 73 (03) :250-269
[2]   Ion channel mutations affecting muscle and brain [J].
Barchi, RL .
CURRENT OPINION IN NEUROLOGY, 1998, 11 (05) :461-468
[3]   MOLECULAR MECHANISM FOR AN INHERITED CARDIAC-ARRHYTHMIA [J].
BENNETT, PB ;
YAZAWA, K ;
MAKITA, N ;
GEORGE, AL .
NATURE, 1995, 376 (6542) :683-685
[4]  
Berkovic S F, 1999, Curr Opin Neurol, V12, P177, DOI 10.1097/00019052-199904000-00008
[5]   The "final common pathway" hypothesis and inherited cardiovascular disease - The role of cytoskeletal proteins in dilated cardiomyopathy [J].
Bowles, NE ;
Bowles, KR ;
Towbin, JA .
HERZ, 2000, 25 (03) :168-175
[6]   Evidence for two concentration-dependent processes for β-subunit effects on α1B calcium channels [J].
Cantí, C ;
Davies, A ;
Berrow, NS ;
Butcher, AJ ;
Page, KM ;
Dolphin, AC .
BIOPHYSICAL JOURNAL, 2001, 81 (03) :1439-1451
[7]   From ionic currents to molecular mechanisms: The structure and function of voltage-gated sodium channels [J].
Catterall, WA .
NEURON, 2000, 26 (01) :13-25
[8]   Structure and regulation of voltage-gated Ca2+ channels [J].
Catterall, WA .
ANNUAL REVIEW OF CELL AND DEVELOPMENTAL BIOLOGY, 2000, 16 :521-555
[9]   STRUCTURE AND FUNCTION OF VOLTAGE-GATED ION CHANNELS [J].
CATTERALL, WA .
ANNUAL REVIEW OF BIOCHEMISTRY, 1995, 64 :493-531
[10]   Disorders of membrane channels or channelopathies [J].
Celesia, GG .
CLINICAL NEUROPHYSIOLOGY, 2001, 112 (01) :2-18