Development of new analgesics based on spinal cord Cyr61-integrin binding inhibition

2020 Fiscal Year Final Research Report

• Project/Area Number: 18K07365
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 51030:Pathophysiologic neuroscience-related
• Research Institution: University of Toyama
• Principal Investigator: Takasaki Ichiro 富山大学, 学術研究部工学系, 准教授 (00397176)
• Project Period (FY): 2018-04-01 – 2021-03-31
• Keywords: Cyr61 / 機械的アロディニア / インテグリン / 小分子拮抗薬 / ケモカイン

Outline of Final Research Achievements

Cyr61 induces pain by binding to β1 integrin. In this study, we aimed to develop an integrin β1 small molecule antagonist. Ten candidate compounds were selected by in silico screening using the Cry61-integrin β1 binding model, and one compound (F) was obtained by in vitro inhibitory activity. However, Compound F did not show a strong analgesic effect. Therefore, we designed a chimeric compound of an existing peptide antagonist and compound F, and succeeded in obtaining compound K, which has a strong inhibitory activity. Compound K exhibited an analgesic effect superior to that of compound F. In the future, we plan to work on the synthesis of derivative compounds of compound K with the aim of acquiring compounds with more potent analgesic effects.

Free Research Field

疼痛学

Academic Significance and Societal Importance of the Research Achievements

Cyr61の痛み慢性化への関与に関する研究は，国内外において我々の研究グループしか行っておらず独自性・新規性は非常に高い。新規鎮痛薬の開発においてターゲット分子の探索研究に限界が生じている現状において，われわれが着目しているCyr61-β1インテグリン系を標的とした創薬は，新薬開発に大きな風穴を開けることができると考えている。本研究において，新規インテグリン阻害化合物の獲得に成功した。引き続き本研究を遂行し成し遂げることで，超高齢化社会の到来と共に，今後本邦で大きく増大することが予想される慢性疼痛患者の福祉に大きく貢献できると考えている。