IonWorks hERG channel assay
Correlation between IonWorks IC50 values and published values obtained using manual patch clamp for seven reference compounds, using PrecisION recombinant hERG cell line (Millipore). Most fall on the line of equivalence (black), or within a 3-fold range of this (blue dotted lines), indicating good correlation between methodologies.
Ion Channels In Drug Discovery and Safety Pharmacology
Ion channels regulate electrical activity in excitable cells, and many roles in non-excitable tissues continue to be uncovered. Ion channels are important therapeutic targets for conditions including arrhythmia, hypertension, local anesthesia, pain, stroke, epilepsy, depression, bipolar disorder, COPD, autoimmune disorders and diabetes. Not only are ion channels important drug targets, but they also regulate safety pharmacology of virtually all drugs. Many drugs have been shown to block the human ether-a-go-go (hERG) ion channel, delaying repolarization of the cardiac action potential. This can initiate the arrhythmia known as Torsades de Pointes (TdP) with fatal consequences.
Recently, automated electrophysiology systems have revolutionized ion channel drug discovery and safety pharmacology testing by facilitating ion channel-focused library screening, medicinal chemistry and safety pharmacology.
Millipore’s Ion Channel Assay Cell Lines, Platforms and Services
Our range of ion channel cell lines underpin a broad portfolio of high-quality and well-validated screening and profiling assays, including CardiacProfiler and IonChannelProfiler services. Our capabilities combine an unrivaled range of ion channel cell lines with both automated (IonWorks®, PatchXpress® systems) and conventional manual electrophysiology platforms. These cell lines are ideal for hERG screening as well as studying voltage-gated and ligand-gated ion channels.
Whether profiling several compounds across a range of ion channels or screening thousands of compounds against a single channel, Millipore can provide a perfect complement to your in-house programs and meet your requirements for turnaround, cost, data and quality.
In Vitro hERG Screening: A Key Early Indicator of Cardiotoxicity
Millipore’s ion channel profiling technologies provide cutting-edge, in vitro testing of compounds for hERG channel blockage. Using robust cell lines generated in-house, we have developed and validated high-quality functional assays for reliable hERG screening in manual patch clamp, PatchXpress and IonWorks systems.
Voltage-Gated Channels
Millipore’s broad selectivity profiling capabilities are well illustrated by our panel of sodium channel assays. These assays are optimized to detect inactivated state- and use-dependence, and are fully validated with known reference standards. As a result, screening against a given subtype, i.e., key pain targets such as Nav1.3, Nav1.7, can be followed up by counter-screening against the other family members for selectivity profiling. More detailed characterization of selected compounds can also be carried out using PatchXpress and/or manual patch clamp systems.
Ligand-Gated Channels
By exploiting recent technical advancements and investing in new technologies, we are developing improved-throughput assays for ligand-gated ion channels, such as GABAA α1/β3/γ2. Our assay correlates well with more conventional assay formats and is capable of detecting ligands with different mechanisms of action. In addition, PatchXpress and manual patch clamp assays are being developed for both fast-gating (e.g. nAChR and GluR6) and other slower-gating receptors (GABAA a1/b3/g2).