Database describing the in silico cardiac safety profile of drugs and their propensity to induce early afterdepolarization

bchristophe By On 28/01/2023 0

The aim of the present database is to describe the in silico cardiac safety profile of drugs and their propensity to induce early afterdepolarization.  This is based on the study of the effects of drugs on the non-failing human ventricular myocyte action potential (endo-, mid- and epicardial subtypes) reconstructed by computational simulation (O’Hara-Rudy dynamic algorithm) in order to identify cardiac action potential abnormalities such as high variations and/or occurrence of resting membrane potential, action potential amplitude, maximal rate of action potential rise, action potential duration, triangulation, early afterdepolarization, transmural dispersion of repolarization, reverse use dependence, qNet or minimal rate of action potential decrease at early afterdepolarization take-off voltage. These various parameters are useful in order to assume a more accurate predictability of pro-arrhythmic liabilities of new drug candidate in the cardiac safety pharmacology screening process, which is the aim of the comprehensive in vitro pro-arrhythmia assay (CiPA) initiative. The in silico cardiac safety profile of each drug (150 drugs described in this first version) is illustrated by a separate page describing the effects induced by each compound on these various parameters. The results are summarized regarding the expected pro-arrhythmia profile of the various compounds as described by the CredibleMeds classification evaluating their propensity to induce torsade de pointes.

v1.0 : 150 drugs described   :    https://doi.org/10.5281/zenodo.7541554

pdf file (poorer graphic quality)  : www.scaptest.com/medias/files/scaptest-in-silico-cardiac-safety-profile-of-drugs-compresse1.pdf

 

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