Abstract
Besides its anti-inflammatory, analgesic and anti-pyretic properties, aspirin is used for the prevention of cardiovascular disease and various types of cancer. The multiple activities of aspirin likely involve several molecular targets and pathways rather than a single target. Therefore, systematic identification of these targets of aspirin can help us understand the underlying mechanisms of the activities. In this study, we identified 23 putative targets of aspirin in the human proteome by using binding pocket similarity detecting tool combination with molecular docking, free energy calculation and pathway analysis. These targets have diverse folds and are derived from different protein family. However, they have similar aspirin-binding pockets. The binding free energy with aspirin for newly identified targets is comparable to that for the primary targets. Pathway analysis revealed that the targets were enriched in several pathways such as vascular endothelial growth factor (VEGF) signaling, Fc epsilon RI signaling and arachidonic acid metabolism, which are strongly involved in inflammation, cardiovascular disease and cancer. Therefore, the predicted target profile of aspirin suggests a new explanation for the disease prevention ability of aspirin. Our findings provide a new insight of aspirin and its efficacy of disease prevention in a systematic and global view.
Highlights
Aspirin, known as acetylsalicylic acid, is a nonsteroidal anti-inflammatory drug (NSAID)
We found several new targets for aspirin which are enriched in the pathways that are strongly involved in inflammatory, cardiovascular disease and cancer, such as vascular endothelial growth factor (VEGF), mitogen-activated protein kinase(MAPK), Fc epsilon RI signaling and arachidonic acid metabolism signaling pathways
We presented a proteome-wide prediction of aspirin targets using structural bioinformatics and system biology approaches
Summary
Known as acetylsalicylic acid, is a nonsteroidal anti-inflammatory drug (NSAID). The primary molecular mechanism of aspirin is the selective acetylaton of Ser-530 of cyclooxygenase-1 (COX-1) (Alfonso et al, 2014; Dovizio et al, 2013; Ghooi, Thatte & Joshi, 1995; Vane, 1971; Vane & Botting, 2003), thereby inhibiting prostaglandin synthesis. This was the basis for its anti-inflammatory, antipyretic, and analgesic effects (Vane & Botting, 2003). Studies on the proteome-wide target profile of aspirin are very limited
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