Table 2.

Examples of large-scale hiPSC-CM chemical screens.

Description	Compounds and Results	hiPSC-CMs	References
Cardioprotection in models of diabetic cardiomyopathy	480 bioactive compounds. Identification of candidate pathways to ameliorate structural disarray.	1 commercial healthy donor and 2 diabetic donors hiPSC-CMs.	(Drawnel et al., 2014)
Cardioprotection in a simulated ischemia model	Confirmation of initial screen ‘hi’ and, subsequently, evaluation of optimized analogues that inhibited MAP4K4 and protect against cell death.	2 commercial healthy donors	(Fiedler et al., 2019)
Action potential shortening in LQT3 and arrhythmia in healthy donor hiPSC-CMs using high content imaging of transmembrane voltage potentials	~170 mexiletine analogues. Refined analogues had increased on target potency and selectivity for desirable on target effects with decreased proarrhythmic liability.	2 LQTS3 hiPSC-CMs plus drug-induced LQTS3 using 3 healthy donor hiPSC-CMs.	(McKeithan et al., 2020)
Proarrhythmic drug screening of field potentials by MEA recording	Kitaguchi et al., and Blinova et al. reference compounds of high, intermediate and low/no arrhythmic risk. Predictivity was in range of 80–90%; greatest for discrimination of high + intermediate from low/no risk compounds.	2 commercial healthy donor hiPSC-CMs.	(Blinova et al., 2018; Kitaguchi et al., 2016)
Cardiotoxicity using kinetic high content imaging of contractility	21 chemotherapeutic kinase inhibitors Good correlation was observed between the in vitro cardiotoxicity (cell viability and loss of contractility) with clinical incidence of cardiotoxicity.	11 healthy donor hiPSC-CMs.	(Sharma et al., 2017)
Proarrhythmic drug screening using kinetic high content imaging of Ca2+ transients	108 reference compounds of high, intermediate and low/no arrhythmic risk. Analysis of individual cells within the fields of view increased sensitivity of detection of proarrhythmic phenotypes such as EADs.	1 commercial healthy donor hiPSC-CM.	(Pfeiffer et al., 2016)