Systems pharmacology strategies for anticancer drug discovery based on natural products
Fang Luo1, Jiangyong Gu, Lirong Chen
1Beijing National Laboratory for Molecular Sciences, State Key Lab of Rare Earth Material Chemistry and Applications, College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, P. R. China. lirongc@pku.edu.cn xiaojxu@pku.edu.cn.
Abstract:
Cancer is a complex disease, known medically as malignant neoplasm. Natural products (NPs) play a very important role in anticancer drug discovery and a large number of NPs have been proven to have potential anticancer effects. Compared with newly synthesized chemical compounds, NPs show a favorable profile in terms of their absorption and metabolism in the body with low toxicity. Searching for multi-target natural drugs can be regarded as a solution to improve therapeutic efficacy and safety. In this work, we collected 104 cancer-associated target proteins from the Protein Data Bank. Based on the Universal Natural Products Database, all of the NPs were docked to 104 cancer-associated target proteins. Then we explored the potential of NPs and several herbs in anticancer drug discovery by using a network-based multi-target computational approach. The NPs with the most potential for anticancer drug discovery and their indications were predicted based on a docking score-weighted prediction model. We also explored the interactions between NPs and cancer target proteins to find the pathological networks, potential drug candidates and new indications.
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