2. Academic Validation
  3. Identification of a Potent Oridonin Analogue for Treatment of Triple-Negative Breast Cancer

Identification of a Potent Oridonin Analogue for Treatment of Triple-Negative Breast Cancer

  • J Med Chem. 2020 Aug 13;63(15):8157-8178. doi: 10.1021/acs.jmedchem.0c00408.
Hong Yao 1,  Shaowen Xie 1,  Xiaoqian Ma 1,  Junkai Liu 1,  Hongyu Wu 1,  Aijun Lin 1,  Hequan Yao 1,  Dahong Li 2,  Shengtao Xu 1,  Dong-Hua Yang 3,  Zhe-Sheng Chen 3,  Jinyi Xu 1
Affiliations

Affiliations

  • 1 State Key Laboratory of Natural Medicines and Department of Medicinal Chemistry, China Pharmaceutical University, 24 Tong Jia Xiang, Nanjing 210009, P. R. China.
  • 2 Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, China.
  • 3 College of Pharmacy and Health Sciences, St. John's University, 8000 Utopia Parkway, Queens, New York 11439, United States.
PMID: 32610904 DOI: 10.1021/acs.jmedchem.0c00408
Abstract

Triple-negative breast Cancer (TNBC) is one of the most highly invasive and metastatic breast cancers without safe and effective therapeutic drugs. The natural product oridonin is reported to be a potential anti-TNBC agent. However, its moderate activity and complex structure hampered its clinical application. In this study, the novel oridonin analogues were first identified by removal of multiple hydroxyl groups and structural simplification of oridonin. The representative analogue 20 exhibited potent Anticancer effects. Further structural modification on 20 generated the most potent derivative 56, which possessed 120-fold more potent antiproliferative activity than oridonin in the TNBC cell line HCC1806. Importantly, compound 56 exhibited more potent Anticancer activity than paclitaxel in TNBC xenograft nude mice. Moreover, 56 could attenuate the expression of MMP-2, MMP-9, p-FAK, and Integrin β1 to inhibit TNBC cell metastasis. All results suggest that compound 56 may warrant further investigation as a promising candidate agent for the treatment of TNBC.

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