FIGURE 1.

An in silico–in vitro pipeline to determine drug cardiotoxicity risk and mechanism. Step 1, the Kernik–Clancy model with experimental artefacts is used to develop a voltage clamp (VC) protocol that is specifically designed to isolate currents. Step 2, spontaneous, I_K1 dynamic clamp and paced action potentials (AP), and optimized VC data are acquired from a patient‐derived induced pluripotent stem cell‐derived cardiomyocyte (iPSC‐CM) before and after drug application. Step 3, the change in I_K1 dynamic clamp and paced AP data from pre‐ to post‐drug application is used to identify AP prolongation, a surrogate marker of cardiotoxicity. Step 4, changes in VC data are used to determine the ion channels targeted by a drug. Step 5, after identifying the ion channel targeted by a drug, a dose–response curve is developed for each of these ion channels using expression line cells.