Activated effector memory T-cells (TEM) have been implicated in the pathogenesis of autoimmune diseases.1 TEM cells express high levels of the voltage-gated potassium channel, Kv1.3, which plays a role in controlling the function of TEM. Inhibition of Kv1.3 reduces the release of pro-inflammatory mediators, inhibits T-cell proliferation and migration to inflamed tissues, and has been shown to ameliorate autoimmune disease symptoms in preclinical animal models. However, small molecule Kv1.3 inhibitors have failed to deliver a successful candidate to the clinic; partly due to a lack of potency and selectivity.
The HESI Cardiac Safety Committee present results from an international ion channel research study that assessed the variability of hERG data generated using automated patch clamp platforms (QPatch 48, Qube 384 and the SyncroPatch 384i) across four different labs.
We developed a high-throughput, electrophysiological assay of TREK-1 function to identify novel modulators. The assay was optimized to identify both activators and inhibitors, providing comprehensive mechanistic data for high value, limited supply screening libraries, such as the venom fraction library used in this study (Targeted Venom Discovery Array, T-VDA, Venomtech, UK).