Specialist ion channel screening to accelerate early-stage screening and lead optimisation

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Fully customised ion channel assays

We understand the importance of robust, reliable assays in enabling you to make timely, well-informed decisions. Using innovative solutions tailored to your specific target, we focus on rapid delivery of high-quality data to accelerate your early-stage compound screening and lead optimisation programmes.

Our specialist team of ion channel scientists are experts in their field. With over 250 years’ collective ion channel drug discovery experience, we specialise in developing, optimising and validating high-quality ion channel screening services using a range of electrophysiology and fluorescence-based platforms.

We fully customise ion channel assays at different stages of the screening cascade, from high-throughput screening (HTS) and structure-activity relationship (SAR) studies, through to specialised biophysical and mechanism-of-action studies for lead compounds.

Example recording of hASIC1a inward current recorded on the Qube automated electrophysiology platform

Figure 1. Example recording of hASIC1a inward current recorded on the Sophion Qube automated electrophysiology platform. Cells are held at -60 mV with ASIC1a activated by the addition of extracellular solution buffered to pH 6.3 (black trace). The effect of inhibitor, diminazene, at 100 nM and 30 µM on the inward current is displayed in the blue and red traces, respectively.

Figure 2. Diminazene concentration-response curve displaying an IC50 of 1.13 µM (pIC50 = 5.95).

Figure 3. The pIC50 values of the reference compound, diminazene, against ASIC1a included in the Qube experiments when supporting Medicinal Chemistry Hit-to-Lead activities.

Reliable data you can trust

Our expertise in electrophysiology and fluorescence-based assays stands us apart, guaranteeing robust and reliable data. We strive to exceed our clients’ expectations and to build long-term partnerships based on trust:
  • High quality, cost-efficient compound screening.
  • Rapid reporting and data interpretation by experienced ion channel experts.
  • Tailored, target-focussed assay development, including complex assays.
  • In-house generation and validation of novel ion channel cell lines.
  • Detailed characterisation of lead compounds in a range of complementary assays.
  • Translational services including confirmation of efficacy.
  • Access to commercially available compound libraries (Assay.Works and Enamine) with freedom to operate.
Ion Channel Screening Resource Library
Nav1.5 late current in WT and Nav1.5-ΔKPQ mutant channels: an automated patch clamp LQT3 electrophysiological assay comparison

The cardiac late Na+ current (late INa) generates persistent inward currents throughout the plateau phase of the ventricular action potential and is an important determinant of repolarisation rate, EADs and arrythmia risk¹. As inhibition of late INa can offset drug effects on hERG and other repolarising K⁺conductances, it is one of the key cardiac channels in the Comprehensive in vitro Pro-arrythmia Assay (CiPA) panel being developed by the FDA to improve human clinical arrythmia risk assessment²̛ ³.

Development of an impedance-based screening assay for cardiac safety and cardiotoxicity detection in stem cell-derived cardiomyocytes

Cardiac toxicity remains the leading cause of new drug safety side-effects. Current preclinical cardiac safety assays rely on in vitro cell-based ion channel assays and ex vivo and in vivo animal models⁽¹⁾. These assays provide an indication of acute risk but they do not always predict the effect of chronic compound exposure, as recently seen with oncology drugs. Therefore, new assays are required to characterise chronic structural and functional effects in human cells earlier in drug discovery. Impedance-based technology can provide more accurate chronic cardiotoxicity measurements in an efficient manner using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs).

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Metrion Biosciences is a contract research organisation (CRO) specialising in high-quality preclinical drug discovery services.
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