Development of novel anti-breast cancer drugs that can induce degradation of estrogen receptor

2016 Fiscal Year Final Research Report

• Project/Area Number: 26860085
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Drug development chemistry
• Research Institution: National Institute of Health Sciences
• Principal Investigator: Shoda Takuji 国立医薬品食品衛生研究所, 有機化学部, 室長 (60435708)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 乳がん治療薬 / 選択的エストロゲン受容体分解薬 / タモキシフェン

Outline of Final Research Achievements

Estrogen receptors (ERs) play a major role in the growth of human breast cancer cells. An antagonist that acts as not only an inhibitor of ligand binding but also an inducer of the down-regulation of ER would be useful for the treatment for ER-positive breast cancer. We designed and synthesized various tamoxifen derivatives that have various lengths and terminal groups of the long alkyl side chain. During the course of our investigation, C10F having a 10-fluorodecyl group on the amine moiety of 4-OHT was shown to be the most potent compound among the tamoxifen derivatives. Moreover, computational docking analysis suggested that the long alkyl chain interacted with the hydrophobic region on the surface of the ER, which is a binding site of helix 12 and coactivator. These results provide useful information to develop promising candidates as SERDs.

Free Research Field

創薬化学