Evidence map›Paper›PMID 41671375›Full record

ArticleScience advances2026

Structure-based design of an opioid receptor modulator for enhanced morphine analgesia.

Yue Wang, Ping Luo, Haiyan Xu, Li Zhan, Kensuke Sakamoto, Mingyu Li, Jing Wang, Xi-Ping Huang, Jianhui Zhou, Tao Liu and 22 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Science advances, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

32 authors.

Yue WangState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.ORCID 0000-0002-3716-2922
Ping LuoState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.ORCID 0000-0002-8167-1900
Haiyan XuState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Li ZhanState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Kensuke SakamotoDepartment of Pharmacology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA.ORCID 0000-0003-4488-1244
Mingyu LiDepartment of Pharmaceutical and Artificial-Intelligence Sciences, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.
Jing WangDepartment of Pharmacology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA.ORCID 0009-0006-3929-9267
Xi-Ping HuangDepartment of Pharmacology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA.ORCID 0000-0002-2585-653X
Jianhui ZhouDepartment of Pharmaceutical and Artificial-Intelligence Sciences, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.ORCID 0000-0001-5403-4888
Tao LiuState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Yanrui SuoState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.ORCID 0000-0003-4673-4547
Wenjia FanState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Xinheng HeState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.ORCID 0000-0001-7813-5480
Youwei XuState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.ORCID 0000-0001-8069-7511
Yongjie CaiState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Chao WangState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.ORCID 0009-0007-6346-3968
Yuxi ZhaoState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Antao DaiState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.ORCID 0000-0003-4241-5346
Yali LaiState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Qingning YuanState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Wen HuState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.ORCID 0009-0003-8361-6432
Kai WuState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Dehua YangState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.ORCID 0000-0003-3028-3243
Xi ChengState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.ORCID 0000-0003-3081-3750
Xiaojie LuState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.ORCID 0000-0002-3600-288X
Brian KrummDepartment of Pharmacology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA.ORCID 0000-0001-6039-4767
Terry KenakinDepartment of Pharmacology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA.ORCID 0000-0002-1550-707X
Jian ZhangDepartment of Pharmaceutical and Artificial-Intelligence Sciences, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.ORCID 0000-0002-6558-791X
Bryan L RothDepartment of Pharmacology, University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA.ORCID 0000-0002-0561-6520
Zhaobing GaoState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.ORCID 0000-0001-8931-5508
H Eric XuState Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.ORCID 0000-0002-6829-8144
Youwen ZhuangDepartment of Pharmaceutical and Artificial-Intelligence Sciences, School of Medicine, Shanghai Jiao Tong University, Shanghai 200025, China.ORCID 0000-0002-1380-8047

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The alarming rates of deaths due to opioid overdose present an urgent need for safer opioid analgesics. Positive allosteric modulators (PAMs) of opioid receptors (ORs) offer a promising approach to enhance opioid efficacy while reducing risks of overdose. In this study, we unveil the selective mechanism of PAM modulation of the OR family through structure elucidation of the δ-opioid receptor and μ-opioid receptor (μOR) bound to orthosteric agonists and PAMs BMS986187 (BMS187) and BMS986122 (BMS122). In addition, we uncovered an unexpected but conserved allosteric site across the transmembrane helices TM2 to TM4 of ORs, occupied by BMS187 but not BMS122. Leveraging these structural insights, we designed 9-(5-(4-chlorophenyl)furan-2-yl)-3,3,6,6-tetramethyl-3,4,5,6,7,9-hexahydro-1

Indexed as

Analgesics, OpioidDrug DesignMorphineReceptors, OpioidReceptors, Opioid, muAllosteric RegulationAllosteric SiteAnalgesiaAnimalsHumansMolecular Dynamics SimulationReceptors, Opioid, deltaStructure-Activity RelationshipAnalgesics, OpioidMorphineReceptors, OpioidReceptors, Opioid, deltaReceptors, Opioid, mu

Identifiers

PMID41671375
PMCPMC12893318

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.