2. Academic Validation
  3. Chemically synthesized LYRM03 could inhibit the metastasis of human breast cancer MDA-MB-231 cells in vitro and in vivo

Chemically synthesized LYRM03 could inhibit the metastasis of human breast cancer MDA-MB-231 cells in vitro and in vivo

  • Bioorg Med Chem Lett. 2019 Jul 15;29(14):1719-1726. doi: 10.1016/j.bmcl.2019.05.027.
Yun-Kai Yang 1,  Da-Dong Shen 2,  Peng He 1,  Liang-Dong Du 3,  Ding-Jian Wan 3,  Pu Wang 2,  Tao Wang 4,  Mei-Qing Feng 5
Affiliations

Affiliations

  • 1 Department of Microbiology and Biochemical Pharmacy, School of Pharmacy, Fudan University, Shanghai 201203, PR China.
  • 2 College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310032, Zhejiang, PR China.
  • 3 Shanghai Laiyi Center for Biopharmaceuticals R&D, 5B, Building 8 200 Niudun Road Pudong District, Shanghai 201203, PR China.
  • 4 Shanghai Laiyi Center for Biopharmaceuticals R&D, 5B, Building 8 200 Niudun Road Pudong District, Shanghai 201203, PR China. Electronic address: [email protected].
  • 5 Department of Microbiology and Biochemical Pharmacy, School of Pharmacy, Fudan University, Shanghai 201203, PR China. Electronic address: [email protected].
PMID: 31126854 DOI: 10.1016/j.bmcl.2019.05.027
Abstract

Aminopeptidase N (APN) belongs to the Aminopeptidase family, which is widely distributed throughout the animal and plant kingdoms. APN is thought to be a very important target for Cancer therapy as it is linked to Cancer progression and metastasis. However, bestatin (Ubenimex) is the only approved drug that targets various aminopeptidases for the treatment of acute myelocytic leukemia and lymphedema. A compound 3-amino-2-hydroxy-4-phenylbutanoylvalylisoleucine (also known as LYRM03), isolated from a Streptomyces strain HCCB10043, exhibited more potent inhibitory activity than bestatin. In this work, we applied a chemical synthesis strategy to generate LYRM03 to overcome the low yields typically achieved from fermentation. Finally, we explored a suite of experiments to determine the bioactivity of LYRM03 and revealed that the metastasis of MDA-MB-231 cells was significantly restrained with LYRM03 treatment or injection both in vitro and in vivo. Because of its anti-metastasis capacity, further structure modifications of LYRM03 will be of interest for its use alone or in combination as a therapy in Cancer.

Keywords

APN/CD13; Breast cancer; LYRM03; MDA-MB-231; Metastasis.

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