Abstract-Angiotensin II (Ang II) type 1 receptor (AT 1 ) antagonists such as losartan (LOS) are widely used for the treatment of hypertension and elicit antiinflammatory and antiaggregatory in vitro and in patients, although the underlying mechanism are unclear. Following computer-based molecule similarity, we proposed that on cytochrome-P450 degradation, the LOS metabolite EXP3179 is generated, which shows molecule homology to indomethacin, a cyclooxygenase inhibitor with antiinflammatory and antiaggregatory properties. Subsequently, serum-levels of EXP3179 were determined for 8 hours in patients receiving a single oral dose of 100 mg LOS. High-performance liquid chromatography followed by liquid chromatography-mass spectrometry (LC-MS) from serum samples revealed a maximum of 10 Ϫ7 mol/L for EXP3179 peaking between 3 to 4 hours. The increase in serum-EXP3179 levels was associated with a significant reduction in platelet aggregation in vivo (Ϫ35Ϯ4%, PϽ0.001 versus control). EXP3179 generation was investigated in a chemical reaction mimicking the liver cytochrome-P450 -dependent LOS-degradation and human endothelial cells were exposed to Ang II or lipopolysaccharides (LPS) in the presence of EXP3179 (10