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May 2013

Doherty KR, Wappel RL, Talbert DR, Trusk PB, Moran DM, Kramer JW, Brown AM, Shell SA, and Bacus S

Multiparameter In Vitro Toxicity Testing of Crizotinib, Sunitinib, Erlotinib, and Nilotinib in Human Cardiomyocytes

Toxicol Appl Pharmacol 272(1):245-55

Publication Date: May 21, 2013

Product Type: iCell Cardiomyocytes

Summary:

Tyrosine kinase inhibitors (TKi) have an established therapeutic value but also have associated cardiotoxicity that is not detected by standard pre-clinical models. iCell Cardiomyocytes and multiparametric analysis correctly predicted the cardiotoxic profile of four FDA-approved TKi molecules that showed unexpected toxicity in humans.

Impact:

The data here demonstrate the value of utilizing functional human cardiac biology in pre-clinical testing to alleviate and avoid costly adverse events in clinical trials and the general population.

Harris K, Aylott M, Cui Y, Louttit JB, McMahon NC, and Sridhar A

Comparison of Electrophysiological Data from Human Induced Pluripotent Stem Cell Derived Cardiomyocytes (hiPSC-CMs) to Functional Pre-clinical Safety Assays

Toxicol Sci 134(2):412-26

Publication Date: May 20, 2013

Product Type: iCell Cardiomyocytes

Summary:

Analysis of the cardiotoxic responses to known ion channel blockers and proprietary GSK compounds using iCell Cardiomyocytes and a multielectrode array (MEA) platform. iCell Cardiomyocytes demonstrate relevant pharmacology that correlates with existing pre-clinical assays.

Impact:

This is the first study to demonstrate that in addition to showing relevant human physiology and pharmacology, iCell Cardiomyocytes’ responses to known cardiotoxic agents correlate to existing pre-clinical assays. Translation between novel iCell Cardiomyocytes assays and other pre-clinical assays is critical for drug discovery and safety studies to be considered in the regulatory environment.