Research and development of novel mu and delta opioid receptor-specific analgesics

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K08686
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Pain science
• Research Institution: National Cancer Center Japan
• Principal Investigator: Uezono Yasuhito 国立研究開発法人国立がん研究センター, 研究所, 分野長 (20213340)
• Co-Investigator(Renkei-kenkyūsha): FUJII Hideaki 北里大学, 薬学部, 教授 (30458757)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: GPCR / オピオイド受容体 / μ/δ二量体化受容体 / トランスレーショナルリサーチ / オピオイド耐性

Outline of Final Research Achievements

ML335, an opioid mu/delta heterodimer-specific agonist discovered in 2013, was reported to have analgesic effects without tolerance. However, in our assay system with mu/delta heterodimerized receptor-expressing cells, the compound seemed to have low efficacy and low potency to the mu/delta receptors. Based on the fact, we sought to construct and discover compounds that have more specific activities to the mu/delta receptors than that of ML335. In the course of screening assay with approximately 100 newly constructed compounds, we found 5 compounds out of 100 possessing higher affinity to the mu/delta receptors but lower affinity to each of mu or delta opioid receptors. We are now trying to take patents of these compounds and also have been constructing novel compounds extremely specific to the mu/delta heterodimerized opioid receptors.

Free Research Field

分子薬理学、疼痛学、緩和医療学