Development of a New Selective Estrogen Receptor Modulator for the Treatment of Endometriosis

• Project/Area Number: 18K09290
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56040:Obstetrics and gynecology-related
• Research Institution: Tottori University
• Principal Investigator: HARADA Tasuku 鳥取大学, 医学部, 教授 (40218649)
• Co-Investigator(Kenkyū-buntansha): 谷口 文紀 鳥取大学, 医学部, 准教授 (40322218)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Project Status: Completed (Fiscal Year 2020)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2020: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2018: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 子宮内膜症 / Estrogen受容体 / 選択的Estrogen受容体調整薬 / 子宮内膜症間質細胞 / 炎症性サイトカイン / 卵巣チョコレート嚢胞 / エストロゲン受容体調整薬 / SR-16234 / 選択的Estrogen受容体調節薬

Outline of Final Research Achievements

The aim of this study is to develop the novel selective estrogen receptor modulators for endometriosis.Our goal is to develop a novel drugs with a completely different mechanism from existing drugs using the endometriosis model mouse and the endometriosis derived-cell culture system.Using a endometriosis model mouse, the efficacy of a new SERM, SR-16234 , on changes in the number of lesions and anti-inflammation action in was investigated.We performed ChIP-seq analysis to validate the responsive genes to SR-16234, and examine their usefulness.

Academic Significance and Societal Importance of the Research Achievements

現在、子宮内膜症の治療としては外科的治療と薬物治療が行われるが、外科的治療の術後再発率が高いことや、現在使用されている薬物治療の薬剤の副作用は問題であり、より安全に長期的に使用できる新しい効果を持った薬剤の開発が必要とされている。現在の薬物療法は
ホルモン剤による薬物療法が主体であり、基本的に排卵抑制による無月経が主要な作用機序である。既存の薬剤とは全く異なる作用機序を持った薬物の開発は長期の症状コントロールや治療を行いながらの妊娠治療に結びつき、子宮内膜症の薬物療法に新しい展開をもたらす。

Research Products

• [Journal Article] Efficacy of Tokishakuyakusan add-on therapy with low-dose oral contraceptive pills on endometriosis patients with dysmenorrhea (2020)
  • Author(s): Izawa M.Taniguchi F.Harada T.
  • Journal Title: J Obstet Gynaecol Res. Volume: 11 Pages: 2280-2286
  • Peer Reviewed / Open Access
• [Journal Article] GATA6 expression promoted by an active enhancer may become a molecular marker in endometriosis lesions (2019)
  • Author(s): Izawa Masao、Taniguchi Fuminori、Harada Tasuku
  • Journal Title: American Journal of Reproductive Immunology Volume: 81 Issue: 2 Pages: 81-81
  • DOI: 10.1111/aji.13078
  • Peer Reviewed / Open Access
• [Journal Article] New insights into the efficacy of SR-16234, a selective estrogen receptor modulator, on the growth of murine endometriosis-like lesions (2018)
  • Author(s): Khine Yin Mon、Taniguchi Fuminori、Nagira Kei、Nakamura Kazuomi、Ohbayashi Tetsuya、Osaki Mitsuhiko、Harada Tasuku
  • Journal Title: American Journal of Reproductive Immunology Volume: 80 Issue: 5 Pages: 80-80
  • DOI: 10.1111/aji.13023
  • Peer Reviewed / Open Access