Sachinidis, Agapios

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HIGHLIGHT REPORT: CARDIOTOXICITY SCREENING

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EXCLI Journal 2016;15:163-165 – ISSN 1611-2156 
Received: February 02, 2016, accepted: February 16, 2016, published: February 22, 2016 
 
 
 
163 
Guest editorial: 
HIGHLIGHT REPORT: CARDIOTOXICITY SCREENING 
 
Agapios Sachinidis 
 
Prof. Dr., Ph.D., Institute of Neurophysiology and Centre for Molecular Medicine Cologne 
(CMMC), Robert-Koch-Str. 39, 50931 Cologne, Germany 
E-mail: a.sachinidis@uni-koeln.de 
 
 
http://dx.doi.org/10.17179/excli2016-180 
 
This is an Open Access article distributed under the terms of the Creative Commons Attribution License 
(http://creativecommons.org/licenses/by/4.0/). 
 
 
 
Recently, Bin Zhao and colleagues from 
the Chinese Academy of Science in Beijing 
and University of California, Sacramento, 
have published a review about identification 
of cardiotoxic compounds by rapid screening 
methods (Li et al., 2015). Cardiotoxicity is 
one of the most frequent causes for with-
drawal of drugs from the market and also 
during drug development (MacDonald and 
Robertson, 2009; Apostolakis et al., 2013; Li 
et al., 2015). Totally, 81 drugs have been 
taken from the market between 1990 and 
2013 (Li et al., 2015). Other drugs, such as 
the antidiabetic rosiglitazone have been 
amended with cautionary notes informing 
about possible cardiotoxicity (Sager et al., 
2015). Therefore, it is of high relevance to 
establish screening methods for identifica-
tion of cardiotoxic compounds and exclude 
them already during an early stage of drug 
development. 
A relatively high number of withdrawn 
drugs have been shown to cause arrhythmia 
by blocking the hERG channel, a potassium 
channel responsible for repolarizing the car-
diac action potential (Li et al., 2015). The 
likelihood to block hERG increases with 
high lipophilicity, the presence of a positive-
ly charged nitrogen atom and the absence of 
negatively charged oxygen atoms (Villou-
treix and Taboureau, 2015). Meanwhile, 
software is available to identify possible in-
teractions with hERG channel functions (re-
viewed in Li et al., 2015). The authors rec-
ommend to first apply these in silico meth-
ods, followed by in vitro screening which 
also includes non-hERG drug targets. For 
this purpose, simple approaches, such as flu-
orescent imaging plate reader based assays 
and Ca²+ dye technologies represent conven-
ient initial steps. Also, human pluripotent 
stem cells (hPSC) derived cardiomyocytes 
have been introduced and several gene and 
microRNA cardiotoxicity markers have been 
identified (Chaudhari et al., 2015, 2016). 
Currently, large efforts are undertaken to es-
tablish alternative methods for toxicity test-
ing, particularly in the fields of liver (Godoy 
et al., 2009, 2013, 2015; Grinberg et al., 
2014), kidney (Yang et al., 2014; Bulacio 
and Torres 2015; Gong et al., 2015) and neu-
rotoxicity (Rempel et al., 2015; Shinde et al., 
2015; Balmer et al., 2014; Krug et al, 2013), 
which are often supported by mathematical 
modeling (Drasdo et al., 2014; Vartak et al., 
2015; Ghallab et al., 2015; Schliess et al., 
2014; Hoehme et al., 2010). The here dis-
cussed review of Li and colleagues gives a 
practical and helpful overview over currently 
available in silio and in vitro technologies 
for cardiotoxicity testing and critically dis-
cusses their possibilities as well as limita-
tions. 
EXCLI Journal 2016;15:163-165 – ISSN 1611-2156 
Received: February 02, 2016, accepted: February 16, 2016, published: February 22, 2016 
 
 
 
164 
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Highlight report: Cardiotoxicity screening

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Highlight report: Cardiotoxicity screening

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