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.

中文翻译：

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基于虚拟筛选的 HSP90 C 末端抑制剂发现策略和网络药理学分析。

背景技术几十年来，HSP90一直被认为是重要的抗癌靶点，但传统的HSP90 N-末端抑制剂经常遭受器官毒性和/或耐药性。方法 HSP90 C 末端抑制剂的开发代表了一种可靠的替代策略。鉴于基于结构鉴定 HSP90 C 末端抑制剂的罕见例子，我们报告了一种基于虚拟筛选的策略，用于从天然产物中发现 HSP90 C 末端抑制剂作为抗癌剂。结果与讨论 来自甘草的 13 种化学成分被确定为可能的 HSP90 抑制剂，其中 3 种已被报道为抗癌剂。通过分子对接预测HSP90 C-末端的结合模式并通过分子动力学模拟进行改进。结论 进一步的网络药理学分析预测了参与癌症通路的总体可能靶点，并揭示了 8 个分子可能与 HSP90 相互作用。建立了基于结构的虚拟筛选策略以发现 HSP90 C 末端抑制剂。