SLL-023ACP, a KOR/MOR dual agonist, produces potent antinociception with fewer side effects
文献类型：期刊论文
| 作者 | Shen, Yi-Quan3,4; Liu, Pan-Wen2,3; Zhang, Deng-Gao5; Liu, Min3; Luo, Jia-Wen1,3; Lin, Yu-Liang5; Gui, Jiang-Wen1,3; Feng, Li-Jin3; Liu, Jing-Gen2,3,4; Li, Wei5 |
| 刊名 | BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
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| 出版日期 | 2026-03-26 |
| 卷号 | 806页码:10 |
| 关键词 | Dual KOR/MOR agonist Antinociception Sedation Conditioned place preference Constipation |
| ISSN号 | 0006-291X |
| DOI | 10.1016/j.bbrc.2026.153411 |
| 通讯作者 | Liu, Jing-Gen(jgliu@simm.ac.cn) ; Li, Wei(wei-li@fudan.edu.cn) ; Wang, Yu-Jun(yjwang@simm.ac.cn) |
| 英文摘要 | Opioids have served as the first-line treatment for pain management. However, their side effects such as addiction potential and constipation have limited their clinical use. Here, we characterized a novel 4,5-epoxymorphinan-based derivative SLL-023ACP, which we previously identified as a high affinity ligand towards x-opioid receptor (KOR) and mu -opioid receptor (MOR). SLL-023ACP was identified as a full KOR agonist (EC50 = 12.84 nM, Emax = 85.69%) and MOR partial agonist (EC50 = 31.21 nM, Emax = 54.49%) in vitro functional cAMP inhibition assay. In vivo, SLL-023ACP displayed potent antinociceptive effects with ED50 values of 2.6 mg/kg in the hot plate test and 0.15 mg/kg in the abdominal constriction test, exhibiting greater potency than KOR agonist U50,488H and MOR agonist Morphine. Its antinociceptive action is effectively reversed by the non-selective opioid antagonist naloxone and the MOR antagonist CTAP in the hot plate test, and by the KOR antagonist nor-BNI in the abdominal constriction test, indicating its analgesic effects was via MOR and KOR. Importantly, at analgesic doses (2.6 and 5 mg/kg), SLL-023ACP induced no conditioned place preference (CPP) and caused less constipation than morphine, although it did produce significant sedation. Taken together, these results suggest that SLL-023ACP is a potent dual KOR/MOR agonist with a favorable profile of potent analgesia with reduced addiction liability and gastrointestinal dysfunction. |
| WOS关键词 | OPIOID RECEPTOR AGONIST ; DISCOVERY ; LIGANDS ; ANALOGS |
| 资助项目 | Natural Science Foundation of Shanghai[2021ZD0203500] ; National Natural Science Foundation of China[23ZR1474900] ; National Natural Science Foundation of China[24ZR1413700] ; Fundamental Research Projects of Science & Technology Innovation and development Plan in Yantai City[82571743] ; Taishan Scholars Program[2024JCYJ045] ; Shandong Laboratory Program ; [SYS202205] |
| WOS研究方向 | Biochemistry & Molecular Biology ; Biophysics |
| 语种 | 英语 |
| WOS记录号 | WOS:001686587000001 |
| 出版者 | ACADEMIC PRESS INC ELSEVIER SCIENCE |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/322984]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Liu, Jing-Gen; Li, Wei; Wang, Yu-Jun |
| 作者单位 | 1.Anhui Univ Chinese Med, Sch Pharm, Hefei 230012, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, 555 Zuchongzhi Rd, Shanghai 201203, Peoples R China 3.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai 264117, Shandong, Peoples R China 4.Zhejiang Chinese Med Univ, Affiliated Hosp 3, Dept Neurobiol & Acupuncture Res, Key Lab Acupuncture & Neurol Zhejiang Prov, 548 Binwen Rd, Hangzhou 310053, Zhejiang, Peoples R China 5.Fudan Univ, Sch Pharmaceut Sci, Dept Med Chem, 826 Zhangheng Rd, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Shen, Yi-Quan,Liu, Pan-Wen,Zhang, Deng-Gao,et al. SLL-023ACP, a KOR/MOR dual agonist, produces potent antinociception with fewer side effects[J]. BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,2026,806:10. |
| APA | Shen, Yi-Quan.,Liu, Pan-Wen.,Zhang, Deng-Gao.,Liu, Min.,Luo, Jia-Wen.,...&Wang, Yu-Jun.(2026).SLL-023ACP, a KOR/MOR dual agonist, produces potent antinociception with fewer side effects.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,806,10. |
| MLA | Shen, Yi-Quan,et al."SLL-023ACP, a KOR/MOR dual agonist, produces potent antinociception with fewer side effects".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 806(2026):10. |
入库方式： OAI收割
来源：上海药物研究所
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