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Current Pharmaceutical Biotechnology

Editor-in-Chief

ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

Research Article

Strategy of Virtual Screening based Discovery of HSP90 C-terminal Inhibitors and Network Pharmacological Analysis

Author(s): Lihong Li, Man Yang, Chenyao Li, Hongyu Xue, Meiyun Shi and Yajun Liu*

Volume 23, Issue 14, 2022

Published on: 11 January, 2022

Page: [1637 - 1646] Pages: 10

DOI: 10.2174/1389201022666210910101419

Price: $65

Abstract

Background: HSP90 has been considered 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 view of rare examples of structure-based identification of HSP90 C-terminal inhibitors, we report 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 towards HSP90 C-terminus were predicted by molecular docking and refined by molecular dynamics simulation.

Conclusion: Further network pharmacological analysis predicted overall possible targets involved in the pathways in cancer and revealed that 8 molecules possibly interact with HSP90. A structure based virtual screening strategy was established for the discovery of HSP90 Cterminal inhibitors.

Keywords: HSP90, virtual screening, network pharmacology, anticancer, molecular dynamics simulation, licorice.

Graphical Abstract

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