Abstract：
:Adverse events resulting from drug therapy can be a cause of drug withdrawal, reduced and or restricted clinical use, as well as a major economic burden for society. To increase the safety of new drugs, there is a need to better understand the mechanisms causing the adverse events. One way to derive new mechanistic hypotheses is by linking data on drug adverse events with the drugs' biological targets. In this study, we have used data mining techniques and mutual information statistical approaches to find associations between reported adverse events collected from the FDA Adverse Event Reporting System and assay outcomes from ToxCast, with the aim to generate mechanistic hypotheses related to structural cardiotoxicity (morphological damage to cardiomyocytes and/or loss of viability). Our workflow identified 22 adverse event-assay outcome associations. From these associations, 10 implicated targets could be substantiated with evidence from previous studies reported in the literature. For two of the identified targets, we also describe a more detailed mechanism, forming putative adverse outcome pathways associated with structural cardiotoxicity. Our study also highlights the difficulties deriving these type of associations from the very limited amount of data available.
journal_name
Chem Res Toxicoljournal_title
Chemical research in toxicologyauthors
Svensson F,Zoufir A,Mahmoud S,Afzal AM,Smit I,Giblin KA,Clements PJ,Mettetal JT,Pointon A,Harvey JS,Greene N,Williams RV,Bender Adoi
10.1021/acs.chemrestox.8b00159subject
Has Abstractpub_date
2018-11-19 00:00:00pages
1119-1127issue
11eissn
0893-228Xissn
1520-5010journal_volume
31pub_type
杂志文章abstract：:Witch hazel ( Hammamelis virginiana) bark is a rich source of both condensed and hydrolizable oligomeric tannins. From a polyphenolic extract soluble in both ethyl acetate and water, we have generated fractions rich in pyrogallol-containing polyphenols (proanthocyanidins, gallotannins, and gallates). The mixtures were...
journal_title：Chemical research in toxicology
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journal_title：Chemical research in toxicology
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journal_title：Chemical research in toxicology
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pub_type： 杂志文章
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更新日期：2011-11-21 00:00:00
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journal_title：Chemical research in toxicology
pub_type： 杂志文章
doi：10.1021/tx990116c
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pub_type： 杂志文章
doi：10.1021/acs.chemrestox.9b00107
更新日期：2019-08-19 00:00:00
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doi：10.1021/tx970140v
更新日期：1998-05-01 00:00:00
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