Strategy of Virtual Screening Based Discovery of HSP90 C-terminal Inhibitors and Network Pharmacological Analysis
Background: HSP90 has been considered as an important anticancer target for several decades, but traditional HSP90 N-terminal inhibitors often suffered from organ toxicity and/or drug resistance. Methods: The development of HSP90 C-terminal inhibitors represents a reliable alternative strategy. In the view of rare examples of structure based identification of HSP90 C-terminal inhibitors, we reported a virtual screening based strategy for the discovery of HSP90 C-terminal inhibitors as anticancer agents from natural products. Results & Discussion: 13 chemical ingredients from licorice were identified as possible HSP90 inhibitors and 3 of them have been reported as anticancer agents. The binding modes of them towards HSP90 C-terminus were predicted by molecular docking and refined by molecular dynamics stimulation. Conclusion: Further network pharmacological analysis predicted overall possible targets involved in the pathways in cancer and revealed that 8 molecules possibly interact with HSP90.