European Journal of Medicinal Chemistry最新文献

{"title":"PET imaging of the opioid system using radioligands: Synthetic approaches and translational applications","authors":"Carlo Reale ,&nbsp;Giuliana Costanzo ,&nbsp;Giuseppe Cosentino,&nbsp;Carmela Parenti ,&nbsp;Lorella Pasquinucci","doi":"10.1016/j.ejmech.2025.117865","DOIUrl":"10.1016/j.ejmech.2025.117865","url":null,"abstract":"<div><div>Opioid receptors (ORs) are members of the G-protein coupled receptor (GPCR) superfamily and are classified into three primary subtypes: mu (MOR), delta (DOR), and kappa (KOR), in addition to the more recently identified opioid receptor-like 1 (ORL-1) subtype. The elucidation of high-resolution crystallographic structures of all opioid receptor subtypes has substantially advanced the rational design and development of opioid-based therapeutics, which are widely employed in the treatment of pain, substance use disorders, addiction, and mood disorders. The opioid system has also been investigated through Positron Emission Tomography, a powerful imaging modality that enables both qualitative and quantitative evaluation of opioid receptor-mediated signalling in the central and peripheral nervous system. Over the past decades, several radioligands with high affinity and selectivity for opioid receptors have been successfully developed for use in preclinical and clinical research. This review provides a comprehensive overview of the main synthetic approaches utilized for the development of opioid receptor radioligands. In addition, the preclinical and clinical applications of the most widely characterized opioid radioligands are critically discussed.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"296 ","pages":"Article 117865"},"PeriodicalIF":6.0,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144268945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to “Synthesis and clinical application of new drugs approved by NMPA in 2023” [European Journal of Medicinal chemistry 283 (2025) 117181/EJMECH-d-24-03758]","authors":"Lijuan Xie, Yingying Wang, Kunyu Wang, Wanying Chen, Fuwei Yang","doi":"10.1016/j.ejmech.2025.117853","DOIUrl":"https://doi.org/10.1016/j.ejmech.2025.117853","url":null,"abstract":"The authors regret &lt; insert corrigendum text&gt;.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"21 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144260321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, synthesis, and biological evaluation of caffeic acid-based novel multifunctional molecules for the management of Alzheimer's disease","authors":"Sunil Kumar, Gyan Modi","doi":"10.1016/j.ejmech.2025.117831","DOIUrl":"https://doi.org/10.1016/j.ejmech.2025.117831","url":null,"abstract":"Alzheimer’s disease (AD) is a multifaceted neurodegenerative disorder characterized by low levels of acetylcholine, oxidative stress, amyloid-beta (Aβ) aggregation, and metal dysregulation. This study aimed to address the limitations associated with natural products for Alzheimer's disease (AD) management by designing and synthesizing in vivo efficacious caffeic acid derivatives as multifunctional cholinesterase inhibitors. A comprehensive structure-activity relationship (SAR) analysis was carried out in a calibrated manner to improve upon the cholinesterase inhibitory potential of caffeic acid along with its multifunctional properties. Among the synthesized compounds, <strong>12d</strong> emerged as a lead molecule, exhibiting selective AChE inhibition (IC₅₀=3.72±0.34 μM) over BChE (IC₅₀=9.65±0.08 μM), with significant improvement over parent caffeic acid (AChE and BChE 35.39 ± 0.66 % and 18.94 ± 0.91 %, respectively). Enzyme kinetic studies revealed <strong>12d</strong> as a mixed inhibition mechanism against human AChE (<em>h</em>AChE) and equine BChE (<em>eq</em>BChE). Molecular docking and molecular dynamics simulations demonstrated that <strong>12d</strong> interacts with key active-site residues of AChE (TRP86, HIS447, SER293, and ARG296), and BChE (TRP82, LEU286, HIS438, PHE329, G197, and TRP231). Additionally, <strong>12d</strong> displayed potent antioxidant activity in the DPPH assay, exhibiting a strong free radical scavenging effect with an IC₅₀ value of 6.32 ± 0.15 μM. <strong>12d</strong> also demonstrated metal-chelating properties, suggesting its potential to prevent metal-induced neurotoxicity. Furthermore, blood-brain barrier (BBB) permeability predictions (<em>Pe</em> = 4.12 ± 0.40) indicated that <strong>12d</strong> can cross the BBB. <strong>12d’s</strong> ability to modulate Aβ_1-42 self-aggregation was confirmed through Thioflavin T (ThT) fluorescence and transmission electron microscopy (TEM) analyses. The neuroprotective potential of <strong>12d</strong> against oxidative stress was further evaluated in SH-SY5Y neuronal cells. Pretreatment followed by the co-treatment with <strong>12d</strong> at varying concentrations effectively protected the cells from H₂O₂-induced neurotoxicity. Also, <strong>12d</strong> significantly reduced intracellular reactive oxygen species (ROS), as MitoSOX and H₂DCFDA assays demonstrated. Finally, in an in vivo scopolamine-induced AD mouse model, <strong>12d</strong> improved spatial memory in the Y-maze test. Moreover, it effectively restored AChE and BChE levels while displaying potent ex vivo antioxidant activity. These findings collectively highlight <strong>12d</strong> as a promising multitarget-directed ligand (MTDL) with therapeutic potential for AD management.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"6 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144260274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bacterial cytidine deaminases as versatile activators of fluoropyrimidine nucleoside prodrugs","authors":"Viktorija Preitakaitė, Arūnas Kazlauskas, Agota Aučynaitė, Kamilė Butkutė, Ringailė Lapinskaitė, Nina Urbelienė, Audrius Laurynėnas, Rolandas Meškys","doi":"10.1016/j.ejmech.2025.117860","DOIUrl":"https://doi.org/10.1016/j.ejmech.2025.117860","url":null,"abstract":"A platform for modification of 5-fluoropyrimidine nucleosides as potential prodrugs has been developed utilizing bacterial-derived cytidine deaminases (CDAs) for activation. It has been demonstrated that CDA_EH, CDA_F14, and CDA_Lsp effectively convert 5-fluoropyrimidine analogs into 5-fluoro-(2'-deoxy)uridine exhibiting cytotoxic effects. Prodrug activation, leading to reduced viability in CDA-expressing cells, has been observed in HCT116, MCF7, and U87MG cancer cell lines. This framework allows the evaluation of various <em>N</em>⁴-acyl/alkyl-5-fluorocytidines, 4-alkylthio-5-fluorouridines, 4-alkoxy-5-fluoro- and 4-alkoxy-5-fluoro-2'-deoxyuridines for their potential use in enzyme-prodrug therapy. Overall, the developed platform provides valuable guidance on selecting both enzyme and prodrug components for the development of effective enzyme-prodrug strategies.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"25 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144260273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, synthesis and evaluation of anti-heart failure activity of O-glucoside derivatives","authors":"Yu Liu, Heng Liu, Xutong Wang, Bing Wang, Xiaodong Fang, Qiming Li, Meng Sun, Kejing Ma, Zeyu Gao, Yong Zhang, Weina Han","doi":"10.1016/j.ejmech.2025.117802","DOIUrl":"https://doi.org/10.1016/j.ejmech.2025.117802","url":null,"abstract":"Heart failure (HF) is a progressive disease characterized by persistent or episodic worsening of symptoms, leading to functional deterioration. Clinically, guidelines recommend the use of SGLT2 inhibitors for the treatment of heart failure. However, the SGLT2 inhibitors exist potential risks including weight loss and euglycemic diabetic ketoacidosis. We designed and synthesized a series of <em>O</em>-glucoside derivatives by introducing nitrogen-containing heterocyclic fragments. Among them, compound E9 showed the most protective effect on the glucose-free DMEM-induced injured cardiomyocytes, and the structure-activity relationships (SAR) of these compounds were preliminarily evaluated in cardiomyocyte injury model. Furthermore, compound E9 significantly enhanced the inhibition of SGLT2, NHE1, and SOD enzyme activity, increased ATP levels in damaged cardiomyocytes, and suppressed Ang II-induced myocardial fibrosis, the autophagy receptor protein P62 and the expression of cell injury markers. Additionally, compound E9 significantly improved cardiac function in TAC-induced HF mice, inhibited cardiomyocyte hypertrophy and collagen deposition, ameliorated myocardial tissue damage, enhanced mitochondrial autophagy in injured cardiomyocytes, and ultimately increased survival rates in HF mice. In conclusion, this study reveals that the novel <em>O</em>-glucoside derivative E9 was a promising compound for the treatment of heart failure.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"51 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144252637","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"AR-A014418-based dual Glycogen Synthase Kinase 3β/Histone Deacetylase inhibitors as potential therapeutics for Alzheimer's disease","authors":"Alan Santini ,&nbsp;Elisa Tassinari ,&nbsp;Alessandra Altomare ,&nbsp;Manuela Loi ,&nbsp;Elisabetta Ciani ,&nbsp;Stefania Trazzi ,&nbsp;Rebecca Piccarducci ,&nbsp;Simona Daniele ,&nbsp;Claudia Martini ,&nbsp;Barbara Pagliarani ,&nbsp;Andrea Tarozzi ,&nbsp;Matteo Bersani ,&nbsp;Francesca Spyrakis ,&nbsp;Daniela Danková ,&nbsp;Eleonora Poeta ,&nbsp;Simone Raimondi ,&nbsp;Lara Davani ,&nbsp;Giancarlo Aldini ,&nbsp;Vincenza Andrisano ,&nbsp;Angela De Simone ,&nbsp;Andrea Milelli","doi":"10.1016/j.ejmech.2025.117838","DOIUrl":"10.1016/j.ejmech.2025.117838","url":null,"abstract":"<div><div>Alzheimer's disease (AD), the most common type of dementia, currently represents an unmet medical need worldwide. It is considered the result of a systemic breakdown of multiple physiological networks which might be adequately tackled by multitarget drugs (MTDs) aimed at restoring the perturbed networks. Accumulating evidence suggests that Glycogen Synthase Kinase 3β (GSK-3β) and Histone Deacetylases (HDACs) synergistically contribute to disease pathogenesis. In a continuation of our efforts to develop MTDs for AD, we manipulated the structure of a previously reported GSK-3β inhibitor, AR-A014418, to develop a new class of dual GSK-3β/HDACs binding agents. Among the 34 synthesized derivatives, compound <strong>19</strong> showed encouraging results, inhibiting GSK-3β (IC₅₀ = 0.04 ± 0.01 μM) HDAC2 (IC₅₀ = 1.05 ± 0.11 μM), and HDAC6 (IC₅₀ = 1.52 ± 0.06 μM). In addition, compound <strong>19</strong> inhibits HDAC2 and 6 activities in cells and blocks tau hyperphosphorylation. Interestingly, it is nontoxic in SH-SY5Y cells up to 100 μM, and exerts neuroprotective effects. Moreover, to better elucidate the mode of action of compound <strong>19</strong>, its effects on the molecular pathways of SH-SY5Y cells were studied using a proteome-wide analysis. We uncovered the potential of compound <strong>19</strong>, which represents a promising hit for the development of innovative disease-modifying agents.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"296 ","pages":"Article 117838"},"PeriodicalIF":6.0,"publicationDate":"2025-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144260275","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, synthesis, and biological evaluation of novel PI3Kδ/HDAC6 dual inhibitors for the treatment of non-Hodgkin's lymphoma","authors":"Yueqi Zuo ,&nbsp;Yongxia Zhu ,&nbsp;Peng Luo ,&nbsp;Nan Huang ,&nbsp;Kun Yao ,&nbsp;Ke Zhang ,&nbsp;Ningyu Wang ,&nbsp;Xingchun Gou","doi":"10.1016/j.ejmech.2025.117852","DOIUrl":"10.1016/j.ejmech.2025.117852","url":null,"abstract":"<div><div>PI3Kδ and HDAC6 inhibitors play important roles in the treatment of lymphoma. Herein, a novel series of purine-based PI3Kδ/HDAC6 dual inhibitors have been rationally designed and synthesized by incorporating an HDAC pharmacophore into our previously reported PI3Kδ inhibitor scaffold. Structure-activity relationship (SAR) studies led to the discovery of the lead compound <strong>22E</strong>, which showed potent inhibitory activity towards PI3Kδ and HDAC6, with IC₅₀ values of 2.4 nM and 6.2 nM, respectively. Compound <strong>22E</strong> showed significantly enhanced antiproliferative activities against multiple non-Hodgkin's lymphoma (NHL) cells compared with either selective PI3Kδ inhibitor or HDAC6 inhibitor, with IC₅₀ values of 34 nM and 53 nM against SU-DHL-6 and JEKO-1 cells, respectively. Subsequent mechanistic studies revealed that compound <strong>22E</strong> effectively arrested the cell cycle in the G0/G1 phase and induced cell apoptosis in SU-DHL-6 and JEKO-1 cells. Meanwhile, <strong>22E</strong> could simultaneously block the PI3K/AKT/mTOR signaling pathway as well as increase the acetylation of α-tubulin and histone H3 levels. In addition, <strong>22E</strong> prevented tumor growth in both SU-DHL-6 and JEKO-1 xenograft models, and there was no observable toxicity. These results demonstrated that <strong>22E</strong> is a promising lead candidate with novel antitumor mechanism for the treatment of NHL.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"296 ","pages":"Article 117852"},"PeriodicalIF":6.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144252624","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design, synthesis, and biological evaluation of novel pyridazinone-based EED inhibitors for prostate cancer","authors":"Zhang-Xu He, Shi-xuan Tan, Zengyangzong Dan, Guan-jun Dong, Yu-lin Liu, Li-Ying Ma, Wen Zhao","doi":"10.1016/j.ejmech.2025.117837","DOIUrl":"https://doi.org/10.1016/j.ejmech.2025.117837","url":null,"abstract":"Aberrant activity of histone methyltransferase polycomb repressive complex 2 (PRC2) is associated with cancers and other diseases. Recently, compounds that bind to the EED subunit of PRC2 have emerged as allosteric inhibitors of PRC2, suggesting that targeting EED represents a novel strategy for human diseases. In this study, we designed and synthesized a new array of pyridazinone-based EED inhibitors derived from hit <strong>6</strong> identified through virtual screening, which was further optimized <em>via</em> extensive structure−activity relationship (SAR) studies. Ultimately, molecule <strong>39</strong> (IC₅₀= 0.62 μM) was identified as a potent EED inhibitor, which not only exhibited potent anti-proliferative activity and high selectivity against prostate cancer PC3 cells, but also could significantly suppress its colony formation and migration. Importantly, compound <strong>39</strong> showed acceptable PK properties and robust tumor regression in the PC3 xenograft model with the tumor growth inhibition reaching nearly 80%. Overall, our study identifies pyridazinone derivative <strong>39</strong> as a novel EED inhibitor, emerging as a promising lead compound warrant further optimization and development for prostate cancer.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"19 1","pages":"117837"},"PeriodicalIF":6.7,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144252601","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel trimethyl lock-based prostate-specific membrane antigen targeted Conjugates: Design, synthesis, and biological activity evaluation","authors":"Jiangzhu Zhan,&nbsp;Lijun Xu,&nbsp;Shuaibing Ding,&nbsp;Ning Ding,&nbsp;Wei Zhang","doi":"10.1016/j.ejmech.2025.117857","DOIUrl":"10.1016/j.ejmech.2025.117857","url":null,"abstract":"<div><div>Prostate cancer, a leading malignancy in men globally, faces challenges such as poor targeting, systemic toxicity, and drug resistance. This study developed an innovative multifunctional linker based on the trimethyl lock (TML) system, enabling parallel conjugation of key modules for targeted drug delivery. The linker integrates three functional components: (1) a targeting module (ACUPA), (2) a drug module (docetaxel, <strong>DTX</strong>), and (3) a trigger module (GSH-responsive disulfide bond). This “three-in-one” design allows flexible adjustment of physicochemical properties. Two conjugates were designed and formulated into nanoparticles. Physicochemical characterization demonstrated their excellent self-assembly and GSH-responsive release properties. Cellular assays showed that the conjugates exhibited comparable inhibitory activity against PSMA-positive 22Rv1 cells to <strong>DTX</strong>, while their activity against PSMA-negative PC 3 cells was lower. Cellular uptake confirmed higher internalization in 22Rv1 cells than in PC 3 cells. In vivo, low-dose <strong>PEG_3.4k-TML-DTX</strong> nanoparticles (10 mg/kg) achieved tumor inhibition rates similar to free <strong>DTX</strong> without causing weight loss, demonstrating favorable biosafety. This study provides a novel strategy for targeted chemotherapy with tumor microenvironment responsiveness and low toxicity.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"296 ","pages":"Article 117857"},"PeriodicalIF":6.0,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144252599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Design of spiro-heterocyclic substituted diaminonaphthalene Keap1-Nrf2 protein-protein interaction inhibitors as novel anti-depressant agents","authors":"Yitong Chen ,&nbsp;Qingqing Qin ,&nbsp;Wenxin Ding ,&nbsp;Ruizhi Yu ,&nbsp;Rui Wang ,&nbsp;Hualong Ji ,&nbsp;Jianyu Yan ,&nbsp;Hao Ma ,&nbsp;Cheng-Shi Jiang ,&nbsp;Yi Sun ,&nbsp;Chunlin Zhuang","doi":"10.1016/j.ejmech.2025.117848","DOIUrl":"10.1016/j.ejmech.2025.117848","url":null,"abstract":"<div><div>Oxidative stress, inflammation and the Keap1-Nrf2 pathway are validated to be related to depression. Theoretically, modulating Keap1 and Nrf2 protein-protein interaction (PPI) should be an effective method to activate Nrf2 for the treatment of major depressive disorders. We previously reported NXPZ-2, a 1,4-diaminonaphthalene, as a Keap1-Nrf2 PPI inhibitor that exhibited promising effects in an Alzheimer's disease (AD) mouse model. However, its pharmacokinetic properties were limited. Herein, we, for the first time, developed a series of heterocyclic substituted diaminonaphthalenes by an “Escape from Flatland” strategy to improve sp³ hybridized carbons. These compounds exhibited strong binding affinity for Keap1. A crystallographic analysis revealed the high-resolution (1.44 Å) binding of <strong>CD-10</strong> with the Keap1 protein, elucidating the complexity of <strong>CD-10</strong>'s binding mechanism. In an LPS-stimulated BV2 cell model, <strong>CD-10</strong> demonstrated the best anti-oxidative stress and anti-inflammatory potential. Furthermore, <strong>CD-10</strong>'s ability to penetrate the blood-brain barrier has been significantly improved. In a chronic unpredictable mild stress (CUMS) mouse model, treatment with <strong>CD-10</strong> effectively alleviated anxiety and depressive behaviors and restored serum neurotransmitter levels by promoting Nrf2 nuclear translocation. Overall, our findings validate that the Keap1-Nrf2 PPI inhibitor holds promise as a preclinical candidate for the treatment of depression.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"296 ","pages":"Article 117848"},"PeriodicalIF":6.0,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144237459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}