European Journal of Medicinal Chemistry最新文献_第9页

A novel luteinizing hormone-releasing hormone (LHRH) receptor-targeting peptide LHRH-III': Design and application for targeted breast cancer therapy 一种新的促黄体生成素释放激素受体靶向肽LHRH- iii '：用于乳腺癌靶向治疗的设计与应用

IF 5.9 2区医学

European Journal of Medicinal Chemistry Pub Date : 2026-03-05 Epub Date: 2026-01-07 DOI: 10.1016/j.ejmech.2026.118563

Boxiang Qiu , Ruihua Fan , Guangxu Si , Jing Wang , Kailun Wang , Guojun Zheng , Xinxin Tian

{"title":"A novel luteinizing hormone-releasing hormone (LHRH) receptor-targeting peptide LHRH-III': Design and application for targeted breast cancer therapy","authors":"Boxiang Qiu , Ruihua Fan , Guangxu Si , Jing Wang , Kailun Wang , Guojun Zheng , Xinxin Tian","doi":"10.1016/j.ejmech.2026.118563","DOIUrl":"10.1016/j.ejmech.2026.118563","url":null,"abstract":"<div><div>Breast cancer is one of the most common malignant tumors among women, with approximately 50–60 % of cases overexpressing the luteinizing hormone-releasing hormone receptor (LHRH-R), making it an important therapeutic target. To overcome the limitations of conventional chemotherapy, this study designed and synthesized a novel LHRH-R-targeting peptide, LHRH-III′, based on the structure of natural LHRH-III with rational structural modifications. Fluorescence labeling experiments demonstrated that this peptide binds to 4T1 cells with an affinity comparable to or superior to that of the classical LHRH-R targeting peptide [D-Lys<sup>6</sup>]-LHRH-I, while its cellular internalization efficiency was increased by more than 6-fold. Subsequently, LHRH-III′ was conjugated to camptothecin (CPT) or doxorubicin (Dox) via a disulfide bond linker to construct peptide-drug conjugates (PDCs). Among these conjugates, LHRH-III′–SS–CPT exhibited more efficient glutathione (GSH)-responsive drug release than LHRH-III′–SS–Dox. In antitumor evaluations, LHRH-III′–SS–CPT demonstrated significant antitumor activity both <em>in vitro</em> and <em>in vivo</em>. Biodistribution studies revealed that hepatic accumulation of LHRH-III′ was only one-sixth of that observed with the control peptide [D-Lys<sup>6</sup>]-LHRH-I, substantially reducing the risk of potential hepatotoxicity caused by off-target accumulation. In summary, the novel targeting peptide LHRH-III′ developed in this study exhibits excellent targeting capability for breast cancer. The lead PDC based on LHRH-III′ (LHRH-III′–SS–CPT) demonstrate promising antitumor efficacy and low toxicity, highlighting their potential application value as a targeted therapeutic strategy for breast cancer.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"305 ","pages":"Article 118563"},"PeriodicalIF":5.9,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145920573","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}

引用次数: 0

Rational design of heparin antagonist: Guanidine-based mimetics unveil key carbohydrate-carbohydrate interactions 肝素拮抗剂的合理设计：胍基模拟揭示了关键的碳水化合物-碳水化合物相互作用

IF 5.9 2区医学

European Journal of Medicinal Chemistry Pub Date : 2026-03-05 Epub Date: 2025-12-31 DOI: 10.1016/j.ejmech.2025.118551

Ankita Chandra , Ana Gimeno , María Payá-García , Preeti Ravindra Bhoge , Virendrasinh Mahida , Jesús Jiménez-Barbero , Raghavendra Kikkeri

{"title":"Rational design of heparin antagonist: Guanidine-based mimetics unveil key carbohydrate-carbohydrate interactions","authors":"Ankita Chandra , Ana Gimeno , María Payá-García , Preeti Ravindra Bhoge , Virendrasinh Mahida , Jesús Jiménez-Barbero , Raghavendra Kikkeri","doi":"10.1016/j.ejmech.2025.118551","DOIUrl":"10.1016/j.ejmech.2025.118551","url":null,"abstract":"<div><div>Small-molecule inhibitors targeting heparin (HP)-protein interactions represent a promising strategy for developing therapeutic agents against serious bleeding complications. Herein, we report a rational design and synthesis of a library of eight trisaccharide HP mimetics incorporating positively charged guanidinium residues aimed at disrupting the ionic interactions of HP and modulating HP-mediated biological activities. The introduction of guanidine residue in HP backbone significantly influenced the conformational plasticity of <span>l</span>-idose and <span>l</span>-iduronic acid, shifting the major <sup>4</sup>C<sub>1</sub>-conformation to predominant <sup>2</sup>S<sub>0</sub>-geometries, akin to the role of high sulfation in native HS. Unlike aminoglycosides, the guanidine-based HP mimetics exhibited no antibacterial activity and demonstrated low cytotoxicity towards both cancerous and normal cell lines. When evaluated as potential antidotes for heparin and fondaparinux-mediated blood coagulation, the highly guanidine-substituted HP mimetics displayed sub-micromolar antagonist potency. NMR studies further confirmed the carbohydrate–carbohydrate interactions between fondaparinux and the HP mimetics, providing a mechanistic basis for the observed activity and introducing a new strategy to block HP-mediated biological functions.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"305 ","pages":"Article 118551"},"PeriodicalIF":5.9,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145895283","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}

引用次数: 0

Synthesis, antidepressant evaluation and computational insights on substituted pyrazoles as selective MAO-A inhibitors 取代吡唑作为选择性MAO-A抑制剂的合成、抗抑郁评价和计算见解

IF 5.9 2区医学

European Journal of Medicinal Chemistry Pub Date : 2026-03-05 Epub Date: 2026-01-02 DOI: 10.1016/j.ejmech.2026.118556

Diksha Choudhary , Rajwinder Kaur , Kailash Jangid , Vinod Kumar , Bhupinder Kumar , Thishana Singh , Amritpal Kaur , Shareen Singh , Manjinder Singh , Thakur Gurjeet Singh , Balakumar Chandrasekaran

{"title":"Synthesis, antidepressant evaluation and computational insights on substituted pyrazoles as selective MAO-A inhibitors","authors":"Diksha Choudhary , Rajwinder Kaur , Kailash Jangid , Vinod Kumar , Bhupinder Kumar , Thishana Singh , Amritpal Kaur , Shareen Singh , Manjinder Singh , Thakur Gurjeet Singh , Balakumar Chandrasekaran","doi":"10.1016/j.ejmech.2026.118556","DOIUrl":"10.1016/j.ejmech.2026.118556","url":null,"abstract":"<div><div>A series of pyrazole derivatives was designed, synthesized, and characterized spectroscopically. All the synthesized compounds were pharmacologically evaluated by <em>in vitro</em> and <em>in vivo</em> methods for their antidepressant activity. Amongst, VK16 and VK19 were the most potent inhibitors of the MAO-A enzyme with IC<sub>50</sub> values of 0.06 ± 0.017 μM and 0.09 ± 0.019 μM, respectively, showing comparable efficacy to that of the reference standards. Additionally, these compounds were tested for their reversibility potential and found to be reversible inhibitors of the MAO-A enzyme, as a 100-fold dilution with the substrate solution restored over 68 % enzymatic activity. The <em>in vivo</em> FST and TST results corroborated well with the findings from <em>in vitro</em> MAO inhibition. Further, antioxidant properties were assessed using <em>in vitro</em> assays and the compounds were computationally analyzed through molecular docking, MD simulation, and DFT studies (<em>in silico</em>). The molecular docking results revealed that the compounds showed stronger interactions with key amino acid residues and better docking scores than the studied standard drugs. All selected compounds demonstrated favorable ADME properties, including good blood–brain barrier penetration and gastrointestinal absorption. Molecular dynamics simulations and DFT studies also confirmed the stability of VK16 and VK19 within the MAO-A binding site. Overall, VK16 and VK19 are emerged as promising antidepressant candidates, warranting further investigation for clinical development.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"305 ","pages":"Article 118556"},"PeriodicalIF":5.9,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145895279","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}

引用次数: 0

Scaffold optimization trends in matrix metalloproteinase inhibitors for selective pancreatic cancer Therapy—A review 选择性胰腺癌治疗基质金属蛋白酶抑制剂支架优化趋势综述

IF 5.9 2区医学

European Journal of Medicinal Chemistry Pub Date : 2026-03-05 Epub Date: 2025-12-30 DOI: 10.1016/j.ejmech.2025.118540

Kyathi Kolli, Dileep Kumar

{"title":"Scaffold optimization trends in matrix metalloproteinase inhibitors for selective pancreatic cancer Therapy—A review","authors":"Kyathi Kolli, Dileep Kumar","doi":"10.1016/j.ejmech.2025.118540","DOIUrl":"10.1016/j.ejmech.2025.118540","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, largely due to its dense stromal barrier, aggressive invasion, and resistance to therapy. Matrix metalloproteinases (MMPs), zinc-dependent endopeptidases responsible for extracellular matrix remodeling, play a critical role in PDAC progression, metastasis, and tumor microenvironment modulation. Consequently, selective inhibition of MMP isoforms has emerged as a promising therapeutic strategy. Early hydroxamate-based MMP inhibitors demonstrated potent activity but failed clinically due to poor selectivity, zinc chelation-related toxicity, and limited pharmacokinetic profiles. Recent medicinal chemistry efforts have focused on scaffold modification to overcome these challenges, leading to the evolution of alternative zinc-binding groups (ZBGs) such as carboxylates, phosphonates, thiols, and sulfonamides. This review systematically summarizes scaffold optimization trends in MMP inhibitors, correlating structural features with enzyme selectivity and anticancer efficacy. Structure–activity relationship (SAR) studies highlight the role of aromatic and polar substituents in enhancing binding affinity and isoform discrimination. Additionally, computational modeling, pharmacophore mapping, and molecular docking analyses provide mechanistic insights into ligand-enzyme interactions within the catalytic Zn<sup>2+</sup> site. The review also discusses crystallographic data and structure-based drug design approaches that guide next-generation MMP inhibitor development. Collectively, this work emphasizes medicinal chemistry strategies for designing potent, selective, and bioavailable MMP inhibitors, thereby advancing rational therapeutic approaches for targeted PDAC management.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"305 ","pages":"Article 118540"},"PeriodicalIF":5.9,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145895304","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}

引用次数: 0

Flavonoids as promising drug leads: Structural diversity, synthetic strategies, and drug-likeness optimization 黄酮类化合物作为有前途的药物先导物：结构多样性、合成策略和药物相似性优化

IF 5.9 2区医学

European Journal of Medicinal Chemistry Pub Date : 2026-03-05 Epub Date: 2026-01-06 DOI: 10.1016/j.ejmech.2025.118549

Chao Yang, Qing Gong, Rong Zhu, Yufan Fan, Qiumeng Wang, Guangbo Ge, Ping Wang

{"title":"Flavonoids as promising drug leads: Structural diversity, synthetic strategies, and drug-likeness optimization","authors":"Chao Yang, Qing Gong, Rong Zhu, Yufan Fan, Qiumeng Wang, Guangbo Ge, Ping Wang","doi":"10.1016/j.ejmech.2025.118549","DOIUrl":"10.1016/j.ejmech.2025.118549","url":null,"abstract":"<div><div>Flavonoids are a major class of natural polyphenolic compounds with diverse physiological and pharmacological activities, and their privileged scaffolds have long attracted interest in natural product based drug discovery. As their physicochemical properties and biological functions are strongly structure-dependent, variations in substitution patterns can markedly influence solubility, membrane permeability, metabolic stability and overall bioactivity. However, the relationships between structural diversity, functional activities, and druggability remain insufficiently summarized. In this review, the biological activities associated with four representative flavonoid subclasses, including flavones, isoflavones, flavonols, and dihydroflavones, are first summarized. It then focuses on the chemical synthesis of these core scaffolds, systematically reviewing the main synthetic strategies developed over the past two decades and comparing their efficiency, safety, and practical feasibility. Given that poor solubility and limited metabolic stability commonly restrict the drug-likeness of natural flavonoids, the review further examines how structural modifications influence physicochemical and pharmacokinetic properties, and summarizes strategies for selective methylation, acylation, glycosylation, halogenation, and arylation. Finally, the structure-activity relationships (SARs) of representative flavonoids are summarized to guide rational structural optimization and the design of improved flavonoid derived drug candidates. Overall, this review integrates advances in pharmacology, synthetic chemistry, and medicinal chemistry, providing strategic insights for the future development of flavonoid based therapeutics.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"305 ","pages":"Article 118549"},"PeriodicalIF":5.9,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145903003","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}

引用次数: 0

Tanshinone IIA derivatives inhibits colorectal cancer growth by targeting pyruvate kinase M2 丹参酮IIA衍生物通过靶向丙酮酸激酶M2抑制结直肠癌生长

IF 5.9 2区医学

European Journal of Medicinal Chemistry Pub Date : 2026-03-05 Epub Date: 2025-12-13 DOI: 10.1016/j.ejmech.2025.118477

Jing Bai , Shengli Liu , Zhiguo Mang , Xueqing Duan , Changfeng Song , Weiyi Tian

引用次数: 0

Broadening the horizon: The promise of PROTACs in non-malignant disorders 拓宽视野：PROTACs在非恶性疾病中的前景

IF 5.9 2区医学

European Journal of Medicinal Chemistry Pub Date : 2026-03-05 Epub Date: 2026-01-14 DOI: 10.1016/j.ejmech.2026.118586

Liping Fu , Gongruixue Zeng , Yu Cao , Yueli He , Yaping Zhao , Chongmei Tian , Jinbai Chen , Hualin Feng , Jianjun Xi , Jingsong Shao , Jianhua Tao

引用次数: 0

Autophagy-tethering compounds (ATTECs) as an emerging and potentially transformative drug discovery approach 自噬系固化合物（attec）是一种新兴的、具有潜在变革性的药物发现方法

IF 5.9 2区医学

European Journal of Medicinal Chemistry Pub Date : 2026-03-05 Epub Date: 2026-01-14 DOI: 10.1016/j.ejmech.2026.118585

Zhi Ying Dorothy Wong , Xinyi Kang , Yaoyao Shi , Rui Fan , Chenchen Zhang , Delin Min , Nannan Sun , Youzhen Ma , Mei-Lin Tang

{"title":"Autophagy-tethering compounds (ATTECs) as an emerging and potentially transformative drug discovery approach","authors":"Zhi Ying Dorothy Wong , Xinyi Kang , Yaoyao Shi , Rui Fan , Chenchen Zhang , Delin Min , Nannan Sun , Youzhen Ma , Mei-Lin Tang","doi":"10.1016/j.ejmech.2026.118585","DOIUrl":"10.1016/j.ejmech.2026.118585","url":null,"abstract":"<div><div>Targeted protein degradation (TPD) strategies leveraging the ubiquitin-proteasome system (UPS), such as proteolysis-targeting chimeras (PROTACs), have gained wide recognition. While the UPS predominantly degrades short-lived soluble proteins, the lysosome-mediated system (LMS) excels at processing larger substrates, including protein aggregates, organelles, and macromolecular complexes. Recently, autophagy-tethering compounds (ATTECs) have emerged as a promising strategy for targeted degradation, harnessing the autophagy-lysosome system (ALS) to enable proximity-induced degradation. These heterobifunctional molecules, composed of LC3-binding warheads and TOI (target of interest) ligands linked together, provide therapeutic potential against disease-causing targets. This review outlines the therapeutic applications of ATTECs in human diseases, highlights recent progress in their development, and explores future opportunities for expanding this emerging class of degradation technologies through ALS from medicinal chemistry perspective.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"305 ","pages":"Article 118585"},"PeriodicalIF":5.9,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145974257","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}

引用次数: 0

Rational design, synthesis and characterization of novel chimeric peptides containing the kappa-opioid agonists CR845 and dynorphin A-derived peptides 含有阿片受体激动剂CR845和肌啡肽a衍生肽的新型嵌合肽的合理设计、合成和表征

IF 5.9 2区医学

European Journal of Medicinal Chemistry Pub Date : 2026-03-05 Epub Date: 2026-01-02 DOI: 10.1016/j.ejmech.2025.118534

Xiaodi Zhang , Shichao Zhang , Shuyuan Wu , Biao Xu , Jiamin Feng , Xuanran Hu , Ning Li , Nan Zhang , Mengna Zhang , Quan Fang

{"title":"Rational design, synthesis and characterization of novel chimeric peptides containing the kappa-opioid agonists CR845 and dynorphin A-derived peptides","authors":"Xiaodi Zhang , Shichao Zhang , Shuyuan Wu , Biao Xu , Jiamin Feng , Xuanran Hu , Ning Li , Nan Zhang , Mengna Zhang , Quan Fang","doi":"10.1016/j.ejmech.2025.118534","DOIUrl":"10.1016/j.ejmech.2025.118534","url":null,"abstract":"<div><div>Recently, κ-opioid receptor (KOR) agonists have been attractive therapeutic candidates for the treatment of pain and pruritus. To advance the development of effective and safer peripherally restricted KOR agonists, we designed, synthesized, and evaluated 21 novel chimeric peptides incorporating the N-terminal tetrapeptide sequence of CR845 and the C-terminal “address” domain derived from dynorphin A. <em>In vitro</em> calcium mobilization assays confirmed the selective and full KOR agonism for all the compounds. Among these, analogues <strong>4</strong>, <strong>9</strong>, and <strong>17</strong> emerged as optimized analogues, exhibiting potent analgesic and antipruritic effects comparable to those of CR845 after subcutaneous administration, through the activation of the peripheral KOR. Additionally, subcutaneous administration of these 3 optimized analogues induced sedation without eliciting aversion or depressive-like side effects. Notably, analogue <strong>4</strong> was selected as the final candidate due to its high potency in KOR agonism and minimal sedative effects, making it the most promising drug candidate for the development of efficient and safe antinociceptive and antipruritic therapies.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"305 ","pages":"Article 118534"},"PeriodicalIF":5.9,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145895278","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}

引用次数: 0

Novel 2,4-thiazolidinedione derivatives as selective AMPKα1 activators for renal ischemia-reperfusion injury therapeutics 新型2,4-噻唑烷二酮衍生物作为肾缺血再灌注损伤治疗的选择性AMPKα1激活剂

IF 5.9 2区医学

European Journal of Medicinal Chemistry Pub Date : 2026-03-05 Epub Date: 2025-12-30 DOI: 10.1016/j.ejmech.2025.118544

Yuanbo Hu , Yuanyuan Cao , Qingsong Chen , Wenhua Tan , Yu Wang , Yan Wu , Yunzhen Deng , Yanlin Wen , Zhuo Chen , Gaoyun Hu , Junxiang Chen , Qianbin Li

{"title":"Novel 2,4-thiazolidinedione derivatives as selective AMPKα1 activators for renal ischemia-reperfusion injury therapeutics","authors":"Yuanbo Hu , Yuanyuan Cao , Qingsong Chen , Wenhua Tan , Yu Wang , Yan Wu , Yunzhen Deng , Yanlin Wen , Zhuo Chen , Gaoyun Hu , Junxiang Chen , Qianbin Li","doi":"10.1016/j.ejmech.2025.118544","DOIUrl":"10.1016/j.ejmech.2025.118544","url":null,"abstract":"<div><div>AMP-activated protein kinase (AMPK) plays a key catalytic role in renal energy metabolism. Its activation confers renoprotection through regulating various downstream pathways. Critically, AMPKα2 activation can exacerbate renal injury by promoting uric acid deposition, highlighting the therapeutic advantage of highly selective AMPKα1 activation for renal ischemia-reperfusion injury (RIRI). Given these considerations, we established an effective screening platform to identify initial hits with AMPKα1 activity. Leveraging these hits, we designed and synthesized a series of thiazolidinedione derivatives as selective AMPKα1 activators. Among these, <strong>22f</strong> demonstrated superior <em>in vitro</em> AMPKα1 activity (EC<sub>50</sub> = 35.1 ± 1.20 nM) and selectivity (176-fold over AMPKα2), coupled with a significant protective effect in NRK-52E cells subjected to hypoxia-reoxygenation injury. Furthermore, in an RIRI mice model, <strong>22f</strong> selectively activated renal AMPKα1, significantly attenuating serum creatinine and blood urea nitrogen levels. Notably, <strong>22f</strong> outperformed the comparator <strong>991</strong> in alleviating kidney damage and reducing cellular infiltration. More importantly, our study provided compelling evidence that selective activation of AMPKα1 could effectively protect against RIRI pathogenesis. <strong>22f</strong> thus emerged as a promising lead compound for the development of novel anti-RIRI therapeutics offering potent efficacy and improved safety profile.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"305 ","pages":"Article 118544"},"PeriodicalIF":5.9,"publicationDate":"2026-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145895284","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}

引用次数: 0