Current Topics in Medicinal Chemistry - Volume 9, Issue 4, 2009

In this issue of Current Topics in Medicinal Chemistry, we highlight several aspects of the medicinal chemistry of ion channels and their relevance in drug discovery by collecting comprehensive reviews from several experts working in this field. As pore-forming proteins that regulate ion transport across the membrane on the basis of concentration and electrochemical gradients, ion channels are ubiquitously distributed in the mem Read More

As trans-membrane proteins located in cytoplasm and organelle membrane, potassium (K+) channels are generally divided into four super-families: voltage-gated K+ channels (Kv), Ca2+-activated K+ channels (KCa), inwardly rectifying K+ channels (Kir) and two-pore domain K+ channels (K2P). Since dysfunctions of K+ channels would induce many diseases, various studies toward their functions in physiologic and Read More

The human ether-a-go-go related gene (hERG) potassium channel is critical to the QT interval in the human heart measured by the electrocardiogram (ECG). The blockade of hERG would induce undesired lethal arrhythmia, named torsades de pointes (TdP), a rare but life-threatening symptom. Although a large number of experimental studies on hERG have been conducted so far, knowledge of how known Read More

Attributed to the extensive researches towards the functions of Kv1.5 gene (also known as KCN5A gene), the therapeutic significances of Kv1.5 channel have been paid special attentions to cardiovascular diseases as well as tumor, the top two public-health problems for the aging population. During recent years, the hindrance for developing cardiovascular drugs is how to discriminate their therapeutic effect from cardiotoxiciti Read More

Potassium ion (K+) channels consist of a ubiquitous family of membrane proteins that play critical roles in a wide variety of physiological processes, such as the regulation of neuronal excitability, muscle contraction, cell proliferation, and insulin secretion. Due to their pivotal functions in biological systems, K+ channels have long been attractive targets for the rational drug design on the basis of their structures and interaction mec Read More

The voltage-gated sodium channels are a family of proteins that control the flow of sodium ions across cell membranes. Considerable data support the hypothesis that hyperexcitability and spontaneous action potential firing in peripheral sensory neurons mediated by voltage-gated sodium channels contribute to the pathophysiology of chronic pain. Sodium channel blockers are, therefore, appealing entities for therapeutic in Read More

The voltage-dependent N-type calcium channel (Cav2.2), which is distributed in the nerve endings of the central and peripheral nerves, is known to be strongly associated with the pathological processes of cerebral ischemia and neuropathic pain. Ziconotide, the chemically synthesized version of the 25-residue peptide marine toxin ω-conotoxin MVIIA, has been approved as an analgesic drug for severe chronic pain treatment. A bl Read More

The voltage-gated sodium channels (VGSCs) play a fundamental role in controlling cellular excitability. Abnormal activity of sodium channels is related to several pathological processes, including cardiac arrhythmias, epilepsy, chronic pain, neurodegenerative diseases and spasticity. In view of this, VGSCs are considered important therapeutic targets for the treatment of these disorders. To date, nine VGSC isoforms have bee Read More