Drug discovery focused on ion-channel proteins began generating great value for pharmaceutical R&D programmes more than 30 years ago, giving rise to medicines still important in the pharmacopeia for treating human disease.
The pharmaceutical industry is facing ever-growing difficulties in developing new drugs and bringing them to market1,2. Many factors stand in the way of R&D productivity, not least of which are shrinking budgets. Yet one of the most pressing challenges continues to be the issue of ensuring that new drug candidates have an acceptable safety profile.
No review of ion channel screening over the past decade can avoid discussing the pivotal role played by automated electrophysiology. Arguably this technology, more than any other, has opened up the field to wider investigation, made ion channels more accessible as drug targets and facilitated the drive towards highest possible data quality. In this review we will hear how automated patch clamping systems are continuing to evolve and are increasingly positioned at the centre of most ion channel discovery activities.
Ion channels are proteins that span cell membranes thus forming conduits or ‘channels’ through which charged ions such as sodium and potassium can pass across a normally impermeant barrier such as the plasmalemma. By so doing, ion channels can mediate a wide variety of physiological functions from the generation of action potentials in nerve cells to immune cell function and more.
Competition in the pharmaceutical industry requires a reduction in research and development project cycle times and, accordingly, an increase in productivity and efficiency. Pharmaceutical companies also are faced with the challenge of translating massive amounts of new genomic data into innovative drugs. More than a thousand possible new drug targets have emerged from sequencing the human genome, but currently available drugs only target approximately 500 different proteins1.
There is an increasing recognition within the pharmaceutical industry of the immense potential for ion channels as a drug target class.Advances in the understanding of the human genome, combined with the introduction of higher throughput electrophysiology platforms, promises a wealth of new opportunities to design potent and selective ion channel targeted therapeutics.
A striking number of drugs targeting ion channels have reached blockbuster status, generating $ billion revenues. In spite of the historical success of ion channels as therapeutic targets and the considerable investment in this target class by the industry, not a single novel, small molecule ion channel drug has been approved by the FDA in the past 10 years.
Significant demand now exists in Pharma and Biotech to access ion channel testing services and this is reflected by the number and the variety of service offerings.