國家衛生研究院 NHRI:Item 3990099045/15995

NHRI > Institute of Biotechnology and Pharmaceutical Research > Shiu-Hwa Yeh > Periodical Articles > Item 3990099045/15995

Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/15995

Title:	Discovery of a mu-opioid receptor modulator that in combination with morphinan antagonists induces analgesia
Authors:	Huang, YH;Lin, SY;Ou, LC;Huang, WC;Chao, PK;Chang, YC;Chang, HF;Lee, PT;Yeh, TK;Kuo, YH;Tien, YW;Xi, JH;Tao, PL;Chen, PY;Chuang, JY;Shih, C;Chen, CT;Tung, CW;Loh, HH;Ueng, SH;Yeh, SH
Contributors:	Institute of Biotechnology and Pharmaceutical Research;Center for Neuropsychiatric Research;NHRI Graduate Student Program
Abstract:	Morphinan antagonists, which block opioid effects at mu-opioid receptors, have been studied for their analgesic potential. Previous studies have suggested that these antagonists elicit analgesia with fewer adverse effects in the presence of the mutant mu-opioid receptor (MOR; S196A). However, introducing a mutant receptor for medical applications represents significant challenges. We hypothesize that binding a chemical compound to the MOR may elicit a comparable effect to the S196A mutation. Through high-throughput screening and structure-activity relationship studies, we identified a modulator, 4-(2-(4-fluorophenyl)-4-oxothiazolidin-3-yl)-3-methylbenzoic acid (BPRMU191), which confers agonistic properties to small-molecule morphinan antagonists, which induce G protein-dependent MOR activation. Co-application of BPRMU191 and morphinan antagonists resulted in MOR-dependent analgesia with diminished side effects, including gastrointestinal dysfunction, antinociceptive tolerance, and physical and psychological dependence. Combining BPRMU191 and morphinan antagonists could serve as a potential therapeutic strategy for severe pain with reduced adverse effects and provide an avenue for studying G protein-coupled receptor modulation.
Date:	2024-07-17
Relation:	Cell Chemical Biology. 2024 Jul 17;Article in Press.
Link to:	http://dx.doi.org/10.1016/j.chembiol.2024.06.013
JIF/Ranking 2023:	http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=2451-9448&DestApp=IC2JCR
Cited Times(Scopus):	https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85200421803
Appears in Collections:	[Shiu-Hwa Yeh] Periodical Articles [Shau-Hua Ueng] Periodical Articles [Chun-Wei Tung] Periodical Articles [Chiung-Tong Chen] Periodical Articles [Chuan Shih(2014-2017)] Periodical Articles [Teng-Kuang Yeh] Periodical Articles [Pao-Luh Tao] Periodical Articles [Others] Periodical Articles [Shu-Yu Lin] Periodical Articles

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