Quantitative and systems pharmacology 4. Network-based analysis of drug pleiotropy on coronary artery disease

Despite recent advance of therapeutic development, coronary artery disease (CAD) remains one of the major issues to public health. The use of genomics and systems biology approaches to inform drug discovery and development have offered the possibilities for new target identification and in silico drug repurposing. In this study, we propose a network-based, systems pharmacology framework for target identification and drug repurposing in pharmacologic treatment and chemoprevention of CAD. Specifically, we build in silico models by integrating known drug-target interactions, CAD genes derived from the genetic and genomic studies, and the human protein-protein interactome. We demonstrate that the proposed in silico models can successfully uncover approved drugs and novel Natural Products in potentially treating and preventing CAD. In case studies, we highlight several approved drugs (e.g., fasudil, parecoxib, and dexamethasone) or Natural Products (e.g., resveratrol, luteolin, daidzein and caffeic acid) with new mechanism-of-action in chemical intervention of CAD by network analysis. In summary, this study offers a powerful systems pharmacology approach for target identification and in silico drug repurposing on CAD.

Coronary artery disease; Drug repurposing; Drug-target network; Genomics; Natural product; Protein-protein interaction; Systems pharmacology.