2. Academic Validation
  3. Synthesis and biological evaluation of anti-cancer agents that selectively inhibit Her2 over-expressed breast cancer cell growth via down-regulation of Her2 protein

Synthesis and biological evaluation of anti-cancer agents that selectively inhibit Her2 over-expressed breast cancer cell growth via down-regulation of Her2 protein

  • Bioorg Med Chem Lett. 2018 Feb 15;28(4):727-731. doi: 10.1016/j.bmcl.2018.01.016.
Anran Zhao 1,  Qiaoyun Zheng 1,  Cody M Orahoske 1,  Nethrie D Idippily 1,  Morgan M Ashcraft 1,  Aicha Quamine 1,  Bin Su 2
Affiliations

Affiliations

  • 1 Department of Chemistry, Center for Gene Regulation in Health and Disease, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH 44115, USA.
  • 2 Department of Chemistry, Center for Gene Regulation in Health and Disease, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH 44115, USA. Electronic address: [email protected].
PMID: 29352646 DOI: 10.1016/j.bmcl.2018.01.016
Abstract

Compound JCC76 selectively inhibited the proliferation of human epidermal growth factor 2 (Her2) over-expressed breast Cancer cells. In the current study, a ligand based structural optimization was performed to generate new analogs, and we identified derivatives 16 and 17 that showed improved activity and selectivity against Her2 positive breast Cancer cells. A structure activity relationship (SAR) was summarized. Compounds 16 and 17 were also examined by western blot assay to check their effect on Her2 protein. The results reveal that the compounds could decrease the Her2 protein, which explains their selectivity to Her2 over-expressed breast Cancer cells. Furthermore, the compounds inhibited the chaperone activity of small chaperone protein that could stabilize Her2 protein.

Keywords

Breast cancer; Her2; Lead optimization; SAR.

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