Highly-validated screening assays developed by Metrion are capable of confidently identifying modulators of the lysosomal TRPML1 channel. The TRPML1 variant that lacks the endo-lysosomal retention sequences (TRPML1-4A) is used, enabling the channel to express at the plasma membrane. As such, channel behaviour can be successfully characterised by:
Read our case study: Development of TRPML1-4A assays across manual, automated patch-clamp, and fluorescence-based platforms
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Optical voltage imaging of human iPSC-derived cardiomyocytes was used to assess electrophysiological effects of compounds beyond hERG inhibition. Action potential waveform analysis revealed compound-specific and concentration-dependent changes, enabling mechanistic differentiation of multichannel activity and demonstrating a human-relevant approach for translational cardiac safety assessment.
Nature Communications paper ‘The nucleobase guanine at the 3′-terminus of oligonucleotide RGLS4326 drives off-target AMPAR inhibition and CNS toxicity'