2. Academic Validation
  3. 5α-Epoxyalantolactone Inhibits Metastasis of Triple-Negative Breast Cancer Cells by Covalently Binding a Conserved Cysteine of Annexin A2

5α-Epoxyalantolactone Inhibits Metastasis of Triple-Negative Breast Cancer Cells by Covalently Binding a Conserved Cysteine of Annexin A2

  • J Med Chem. 2021 Sep 9;64(17):12537-12547. doi: 10.1021/acs.jmedchem.1c00267.
Mingming Wei 1,  Yunyun Zhou 1 2,  Chong Li 1,  Yuyu Yang 1 2,  Tongtong Liu 1 2,  Yulin Liu 1,  Yujiao Wei 1,  Ning Liu 1,  Shuangwei Liu 1 2,  Qianqian Wang 1,  Sheng Cao 1,  Yue Sun 1 2,  Pengzhen Sheng 1 2,  Cheng Lu 1,  Cheng Yang 1 2,  Xiang Liu 1,  Guang Yang 1
Affiliations

Affiliations

  • 1 The State Key Laboratory of Medicinal Chemical Biology, College of Life Sciences, College of Pharmacy, Nankai University, Tianjin 300071, P. R. China.
  • 2 Tianjin Key Laboratory of Molecular Drug Research, Tianjin International Joint Academy of Biomedicine, Tianjin 300457, P. R. China.
PMID: 34351142 DOI: 10.1021/acs.jmedchem.1c00267
Abstract

Triple-negative breast Cancer (TNBC) has been considered the most aggressive and mortal breast Cancer. Thus far, it remains an important challenge to develop TNBC targeted therapy. As revealed from numerous recent studies, ANXA2 may be a potential target to treat TNBC. In the present study, a natural product 5α-epoxyalantolactone (5α-EAL) was discovered as an anti-breast Cancer Stem Cells (BCSCs) lead compound. Furthermore, 5α-EAL was found to be able to notably suppress the function of ANXA2 by covalently targeting cysteine 9 (Cys9) of ANXA2. To the best of our knowledge, 5α-EAL was recognized as the first small molecule functional inhibitor of ANXA2. It could significantly inhibit the formation of the heterotetrameric complex of ANXA2 and S100A10, which is capable of transporting E-cadherin (E-Ca) to the membrane. The above findings may be used as a possible strategy to develop novel anti-TNBC therapies targeting ANXA2.

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