Bioorganic & Medicinal Chemistry最新文献

{"title":"Design, synthesis, and evaluation of antipyrine and nicotinic acid derivatives as anti-inflammatory agents: in vitro and in vivo studies","authors":"Rasha A. Hassan ,&nbsp;Soha H. Emam ,&nbsp;Demiana S. Mikhail ,&nbsp;Soha O. Hassanin ,&nbsp;Mona G. Khalil ,&nbsp;Amr M. Abdou ,&nbsp;Eman O. Osman","doi":"10.1016/j.bmc.2025.118439","DOIUrl":"10.1016/j.bmc.2025.118439","url":null,"abstract":"<div><div>A series of new antipyrine and nicotinic acid-based scaffolds were synthesized and evaluated for their inhibitory activity against cyclooxygenase-1 and cyclooxygenase-2, using indomethacin and celecoxib as reference drugs. Among the synthesized compounds, <strong>4d</strong> and <strong>6b</strong> demonstrated the most potent COX-2 inhibition, exhibiting IC₅₀ values of 0.940 ± 0.05 μM and 0.614 ± 0.03 μM, respectively, in comparison to celecoxib (IC₅₀ = 0.844 ± 0.04 μM). Compound <strong>4d</strong> displayed the highest COX-2 selectivity index (SI = 13.57), surpassing that of celecoxib (SI = 7.92), thereby indicating superior COX-2 selectivity. Consequently, the <em>in vivo</em> anti-inflammatory activity of compound <strong>4d</strong> was comparable to that of indomethacin. Compound <strong>4d</strong> significantly reduced paw edema, achieving edema inhibition percentages of 14.75 %, 30.77 %, and 45.33 % at the first, second, and third hours, respectively. In contrast, celecoxib exhibited the most pronounced anti-inflammatory effect, achieving edema inhibition percentages of 59.02 %, 69.23 %, and 78.67 % at the corresponding time points. Histopathological examination confirmed the absence of gastric ulceration following oral administration of compound <strong>4d</strong>. Furthermore, it effectively lowered serum levels of prostaglandin E2 and interleukin-1β. To elucidate its selectivity and binding affinity, molecular docking of compound <strong>4d</strong> into the COX-2 active site was conducted, revealing favorable interactions consistent with its biological activity. Collectively, these findings identify compound <strong>4d</strong>, an antipyrine–urea hybrid with para-Cl and meta-CF₃ substitutions, as a useful lead scaffold for effective, safe, and selective COX-2 inhibitors.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"132 ","pages":"Article 118439"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145297737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Helix stabilization by i,i + 7 amine-containing hydrocarbon Staples: Effects of length, stereochemistry, and orientation","authors":"Ha T.N. Nguyen ,&nbsp;Su-Yeon Lee ,&nbsp;Duc V.H. Tran ,&nbsp;Young-Woo Kim","doi":"10.1016/j.bmc.2025.118443","DOIUrl":"10.1016/j.bmc.2025.118443","url":null,"abstract":"<div><div>We previously introduced the <em>i</em>,<em>i</em> + 4 amine-containing hydrocarbon (ACH) stapling system as a helix-stabilizing alternative to conventional all-hydrocarbon (AHC) staples, offering improved aqueous compatibility and chemical tunability. Here, we extend this approach to the <em>i</em>,<em>i</em> + 7 topology, which spans two helical turns and enables long-range conformational control. Systematic variation of cross-link length, stereochemistry, and orientation identified a 13-atom butylaminoalkenyl tether with <em>S</em><img><em>S</em> configuration as the most effective helix-stabilizing <em>i</em>,<em>i</em> + 7 ACH staple. Notably, orientation reversal substantially enhanced helicity relative to the canonical arrangement, and this effect proved transferable across helical registers. Furthermore, the orientation-optimized staple not only reinforced α-helical conformation but also conferred significant proteolytic resistance, thereby revealing a direct link between structural preorganization and biochemical resilience. Taken together with earlier <em>i</em>,<em>i</em> + 4 variants, <em>i</em>,<em>i</em> + 7 ACH staples constitute a coherent design platform that expands the chemical and functional space of peptide stapling, with broad implications for structurally reinforced, therapeutically relevant α-helical peptides.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"132 ","pages":"Article 118443"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145311930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel trifluoromethylquinoline derivatives as potent tubulin polymerization inhibitors with antitumor activity","authors":"Mengsha Mao ,&nbsp;Liangliang Hu ,&nbsp;Xiangkai Kong ,&nbsp;Shijiao Wei ,&nbsp;Ping Yi ,&nbsp;Gang Yu ,&nbsp;Guangcan Xu ,&nbsp;Jia Yu ,&nbsp;Sha Cheng ,&nbsp;Xiaoping Zeng ,&nbsp;Kun Liu ,&nbsp;Bixue Xu ,&nbsp;Heng Luo ,&nbsp;Xueling Meng","doi":"10.1016/j.bmc.2025.118472","DOIUrl":"10.1016/j.bmc.2025.118472","url":null,"abstract":"<div><div>Herein, two series of <em>N</em>-aryl-2-trifluoromethyl-quinoline-4-amine derivatives as tubulin polymerization inhibitors were designed and synthesized. Compounds <strong>14b</strong> exhibited potency inhibitory activity against LNCaP cells (IC₅₀ = 0.0027 μM and Selectivity Index = 4.07) which was more effective than the positive control colchicine, while compounds <strong>12</strong>, <strong>16a</strong>, and <strong>14e</strong> exhibited moderate activity against LNCaP cells with IC₅₀ values of 0.28, 0.0413, and 0.43 μM, respectively. Moreover, mechanism studies showed that <strong>14b</strong> could disrupt tubulin polymerization effectively, block cell cycle in G2/M phase, and induced cellular apoptosis. <strong>14b</strong> significantly inhibited LNCaP cell migration and invasion. Meanwhile, SwissADME predictions showed that <strong>14b</strong> has good pharmacokinetic properties and molecular docking confirmed that it may bind to the colchicine binding site. In brief, these data suggested that <strong>14b</strong> was a promising lead compound with antitumor activity for discovering novel tubulin polymerization inhibitors.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"132 ","pages":"Article 118472"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145494235","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis and degradation effect of PROTACs targeting EGFR triple mutants","authors":"Xiao-Xiao Xi,&nbsp;Hong-Yi Zhao,&nbsp;Minhang Xin,&nbsp;Shuai Mao,&nbsp;San-Qi Zhang","doi":"10.1016/j.bmc.2025.118427","DOIUrl":"10.1016/j.bmc.2025.118427","url":null,"abstract":"<div><div>Drug resistance caused by epidermal growth factor receptor (EGFR) mutation has significantly limited the clinical efficacy of EGFR tyrosine kinase inhibitors (EGFR-TKIs). In this study, we selected fourth-generation EGFR-TKIs (compounds <strong>A</strong>, <strong>B</strong>, and <strong>C</strong>) and EGFR-TKI <strong>D</strong> as ligands for EGFR, along with VHL-L1 and VHL-L2 as ligands for the E3 ligase, using acyl linkers to design novel PROTACs targeting EGFR triple mutants. We synthesized and evaluated compounds EP1–EP12. Among them, <strong>EP7</strong>, <strong>EP8</strong>, <strong>EP9</strong>, <strong>EP11</strong> and <strong>EP12</strong> exhibited potent antiproliferative activities against cells expressing EGFR mutants. Notably, <strong>EP9</strong> and <strong>EP12</strong> effectively induced the degradation of EGFR triple mutants (EGFR^{Del19/T790M/C797S} and EGFR^{L858R/T790M/C797S}) and significantly suppressed EGFR pathway signal transduction. Mechanism studies revealed that the degradation process requires the formation of ternary complexes and the ubiquitination of the EGFR protein, with the degradation being associated with lysosomal activity. In conclusion, compounds EP9 and EP12 were identified as potent degraders of EGFR triple mutants, offering new insights into the development of PROTACs for targeting these mutations.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"132 ","pages":"Article 118427"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145264923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of novel 20S proteasome activators for hypoxic cardiomyocyte protection via endoplasmic reticulum stress alleviation","authors":"Dan Wu ,&nbsp;Yu Cao ,&nbsp;Yubing Han ,&nbsp;Linhao Xu ,&nbsp;Han Han ,&nbsp;Yaoli Shi ,&nbsp;Jiayi Ma ,&nbsp;Qingyi Wang ,&nbsp;Lixin Gao ,&nbsp;Mingzhi Wang ,&nbsp;Jianjun Xi ,&nbsp;Jingjing Sun ,&nbsp;Huajian Zhu ,&nbsp;Jiaan Shao ,&nbsp;Bin Ju ,&nbsp;Yizhou Xu ,&nbsp;Yubo Zhou ,&nbsp;Jiankang Zhang","doi":"10.1016/j.bmc.2025.118452","DOIUrl":"10.1016/j.bmc.2025.118452","url":null,"abstract":"<div><div>Under hypoxic stress, cardiomyocytes predominantly depend on 20S proteasome-mediated degradation to clear accumulated and misfolded proteins. The resultant proteotoxic stress from impaired protein homeostasis contributes significantly to the pathogenesis of cardiovascular disorders. Pharmacological enhancement of 20S proteasome activity thus represents a novel therapeutic paradigm for ischemic cardiomyopathy by restoring proteostasis in myocardial cells. In this study, the hit compound <strong>X-1</strong> was identified through screening of proteasome activation profile. Subsequent structure-activity relationship optimization yielded a series of highly potent activators. Intracellular protein degradation assessment revealed that these compounds possessed abilities to alleviate endoplasmic reticulum stress, as demonstrated by the luciferase reporter system. Additionally, selected compound <strong>B3</strong> exhibited superior cytoprotection, increasing viability of hypoxia-injured cardiomyocytes while downregulating ER stress markers CHOP and Grp78 at the protein level. AlphaFold3-predicted binding modes and 100 ns molecular dynamics simulations revealing its stabilization of the <em>α</em> region to induce proteasome gate opening, thereby establishing a structure-function rationale for its 20S activation mechanism.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"132 ","pages":"Article 118452"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145407808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of Psidium meroterpenoids with anti-hepatocellular carcinoma activities","authors":"Zhuo Wang ,&nbsp;Chunngai Hui","doi":"10.1016/j.bmc.2025.118481","DOIUrl":"10.1016/j.bmc.2025.118481","url":null,"abstract":"<div><div>Liver cancer presents as a significant human disease, and hepatocellular carcinoma appears as the most common form of liver cancer. Several therapeutic agents, such as sorafenib, are currently in Phase III clinical trials for the treatment of liver cancer. However, the development of potent and effective pharmaceuticals is undoubtedly crucial to managing the status of liver cancer and improving the quality of life of patients. <em>Psidium</em> meroterpenoids are natural products isolated from the leaves of <em>Psidium guajava</em> L., exhibiting potent cytotoxicity to hepatocellular carcinoma cell lines. Being synthetically accessible, <em>Psidium</em> meroterpenoids show tremendous potential as a therapeutic agent for hepatocellular carcinoma. This perspective outlines the biological profile, biosynthetic pathway, and chemical synthesis of <em>Psidium</em> meroterpenoids, as well as future directions and opportunities.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"132 ","pages":"Article 118481"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145538274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"D-DARTS: an alternative method for NaV1.5 affinity molecules identification based on dual-drug affinity responsive target stability","authors":"Zirui Lü,&nbsp;Xiandong Dai,&nbsp;Huixia Li,&nbsp;Cunlin Wang,&nbsp;Fanhua Meng","doi":"10.1016/j.bmc.2025.118436","DOIUrl":"10.1016/j.bmc.2025.118436","url":null,"abstract":"<div><div>Drug affinity responsive target stability (DARTS) is a powerful label-free technique for detecting target engagement by measuring the increased resistance of a protein to proteolytic degradation upon ligand binding. However, its application to multi-transmembrane channel proteins has been limited due to their intrinsic structural instability and general resistance to protease digestion. To address this challenge, we developed a novel strategy termed Dual-DARTS (D-DARTS), which employs controlled proteolysis in an SDS-containing denaturing buffer to evaluate a target protein's dual stability—namely, resistance to both chemical denaturation and enzymatic degradation. Using this approach, we successfully identified affinity ligands for the NaV1.5 channel, including both inhibitors and agonists. Notably, D-DARTS enabled the discovery of poneratoxin, a peptide derived from bullet ants, as a high-affinity binder to NaV1.5, a finding validated through electrophysiological assays. Preliminary molecular docking analyses suggested that poneratoxin binds to an epitope analogous to that of the alkaloid agonist BTX<img>B. The general utility of the D-DARTS method was further corroborated by its successful application to the mitochondrial membrane protein VDAC1. By enabling target profiling based on binding affinity rather than functional activity, D-DARTS provides a complementary alternative to electrophysiology-based screening for NaV1.5 channel binders, with advantages including operational simplicity, cost-efficiency, and reduced reliance on specialized equipment. This strategy is anticipated to be applicable to target identification and active molecule screening for a wide range of channel proteins and other multi-transmembrane proteins.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"132 ","pages":"Article 118436"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145290492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tissue transglutaminase inhibitors over the past decade","authors":"Brianna Ryan ,&nbsp;Sarah Tribe ,&nbsp;Jeffrey W. Keillor","doi":"10.1016/j.bmc.2025.118476","DOIUrl":"10.1016/j.bmc.2025.118476","url":null,"abstract":"<div><div>Tissue transglutaminase (TG2) is a multifunctional protein that functions as a protein cross-linking enzyme and also as an intracellular G-protein. It has been implicated in numerous disorders such as celiac disease, fibrosis and different cancers. Due to these diverse pathologies, there is a need to develop a range of inhibitors that can target the different functionalities of TG2. In this review, we present the latest inhibitors published over the past decade, specifically focussing on irreversible inhibitors (peptidomimetic and small-molecule), probes, and reversible inhibitors.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"132 ","pages":"Article 118476"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145522588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacophore-based high-throughput virtual screening (HTVS) to identify new c-Src kinase inhibitors with anticancer potential","authors":"Ali M. Alaseem ,&nbsp;Summya Rashid ,&nbsp;J. Puneetha ,&nbsp;M. Arockia Babu ,&nbsp;Glowi Alasiri ,&nbsp;Thakur Gurjeet Singh ,&nbsp;Yogita Tyagi ,&nbsp;Mohammad Suhail Akhter ,&nbsp;Anand Mohan Singh ,&nbsp;Nisha Bansal","doi":"10.1016/j.bmc.2025.118451","DOIUrl":"10.1016/j.bmc.2025.118451","url":null,"abstract":"<div><div>c-Src is the non-receptor kinase commonly overexpressed in numerous cancer isoforms. As potential anticancer target, these receptors are difficult to target with drugs because of their continuous shuttling between cellular and nuclear compartments and role in relaying of vital signals for gene expression, cell growth, and survival. Besides this high structural homology to other kinases, the involvement of compensatory pathways and the availability of multiple domains within the same proteins further complicate the targeting by drugs. The toxicity and resistance issue with the handful of c-Src inhibitors available, which are again non-selective in approach, further complicate this process. Considering the gap, we employed a drug identification strategy for a plausible c-Src inhibition and its anticancer potential. We selected 500,000 small molecules from the ChemBridge commercial library (database) for the virtual screening. These molecules were filtered via the development of a pharmacophore model, in silico pharmacokinetics (ADME) analysis, and high-throughput virtual screening (HTVS). The top-ranked molecules based on the docking scores, which represent computational binding affinity between a protein and a ligand, were selected and eventually led to 29 best docked molecules. The visual inspection further resulted in refinement of 4 molecules (5280699, 9797370, 11200016, and 71736582), demonstrating protein–ligand interactions the most at the c-Src kinase binding site. To validate their optimal binding, we carried out 200 ns MD simulations on these four selected proteins–ligand complexes. MD analysis revealed that the inhibitors 11200016 and 71736582 were found to be exceptionally stable at the c-Src kinase binding site, meeting the essential prerequisite. The top hit, 71736582, was further corroborated biologically. 71736582 portrayed excellent anticancer potential towards various cancer cell lines (A549, MDAMB-231, HCT-116, DU-145, and PC-3). It was found to inhibit the c-Src-mediated kinase activity (IC₅₀: 517 nM) in comparison to the positive control, bosutinib (IC₅₀: 408 nM). The compound was also able to increase the oxidative stress and induce apoptosis in the colorectal cancer cells employed. The study thus may pave the way for exploration of the top identified ligands further to develop and establish their potential as c-Src kinase inhibitors with anticancer potential.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"132 ","pages":"Article 118451"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145399252","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery, SAR, and molecular basis of (R)-1-((3R,4S)-3-((dimethylamino)methyl)-4-hydroxy-4-(3-methoxyphenyl)piperidin-1-yl)-3-(3-fluorophenyl)-2-methylpropan-1-one as a novel potent analgesic","authors":"Xiaodi Xu ,&nbsp;Haoran Zhu ,&nbsp;Qingbo Shao ,&nbsp;Baiyu Chen ,&nbsp;Jing Lin ,&nbsp;Yang Gao ,&nbsp;Zhenzhou He ,&nbsp;Wei Fu ,&nbsp;Wei Li","doi":"10.1016/j.bmc.2025.118474","DOIUrl":"10.1016/j.bmc.2025.118474","url":null,"abstract":"<div><div>Opioid analgesics remain a cornerstone of pain management, among which μ-opioid receptor (MOR) agonists dominate clinical practice due to their well-established efficacy. However, dose related adverse effects (<em>e.g.</em>, respiratory depression, addiction potential) constrain their therapeutic utility, driving sustained efforts to develop novel MOR agonists with improved safety profiles. Building upon our previously identified lead compound <strong>FWB2</strong>, a series of 3-((dimethylamino)methyl)-4-(3-methoxyphenyl)piperidin-4-ol derivatives was designed <em>via</em> structure-based drug design (SBDD), synthesized, and systematically evaluated through comprehensive <em>in vitro</em> and <em>in vivo</em> pharmacological profiling. Systematic structure-activity relationship (SAR) exploration identified (<em>R,</em> (3<em>R,</em>4<em>S</em>))-<strong>6c</strong> as a novel and selective MOR agonist (MOR <em>K</em>_<em>i</em> = 0.9 nM, MOR: DOR: KOR = 1: 561.1: 188.3; MOR EC₅₀ = 89.9 nM), demonstrating potent antinociceptive activity (ED₅₀ = 1.63 mg/kg) in the hot plate model. Molecular docking studies elucidated the binding mode of (<em>R,</em>(3<em>R,</em>4<em>S</em>))-<strong>6c</strong> with the MOR, identifying its molecular interactions with four critical residues W318^7.35, D147^3.32, H54 and W293^6.48, while delineating the structural features of the ligand-receptor binding pocket.</div></div>","PeriodicalId":255,"journal":{"name":"Bioorganic & Medicinal Chemistry","volume":"132 ","pages":"Article 118474"},"PeriodicalIF":3.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145450274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}