Thursday, November 21, 2013
This week in techniques
Publication and contact
Analysis of adverse events
database to identify mechanisms underlying side effects
In silico and mouse studies suggest analysis of adverse
events database can identify new targets that separate beneficial therapeutic
effects from adverse events. In the FDA Adverse Event Reporting System
(FAERS) database, incidence of myocardial infarction (MI) was lower in patients
than patients taking Avandia alone. Network interaction analysis showed that
pathways activated by Byetta and Avandia intersected at plasminogen
activator inhibitor 1 (SERPINE1;
In a mouse model of diabetes, Avandia and Byetta normalized Pai1 levels and
decreased clotting dynamics compared with Avandia alone. Next steps include
identifying pathway interaction nodes for other drug combinations and testing
in preclinical models.
Avandia and the glucagon-like
peptide-1 receptor (GLP-1R;
agonist Byetta are marketed to treat diabetes by GlaxoSmithKline
plc and Bristol-Myers
Squibb Co., respectively.
Published online Nov. 21, 2013
Patent application filed;
available for licensing
Zhao, S. et al. Sci.
Transl. Med.; published online Oct. 9, 2013;
Contact: Ravi Iyengar, Icahn School of Medicine at Mount
Sinai, New York, N.Y.
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