European Journal of Medicinal Chemistry最新文献

{"title":"Targeting RIPK1-mediated necroptosis, oxidative stress, and ferroptosis: A novel multitarget therapy for ischemic stroke","authors":"Ziwei Song ,&nbsp;Liang Ye ,&nbsp;Yunjie Wang ,&nbsp;Wenyan Wang ,&nbsp;Chunjiao Liu ,&nbsp;Jing Lu ,&nbsp;Jiajing Zhang ,&nbsp;Hongbo Wang ,&nbsp;Jianzhao Zhang ,&nbsp;Yifei Yang ,&nbsp;Jingwei Tian","doi":"10.1016/j.ejmech.2025.117884","DOIUrl":"10.1016/j.ejmech.2025.117884","url":null,"abstract":"<div><div>Ischemic stroke is characterized by high mortality and disability rates, and involves complex pathological processes mediated by multiple damage cascade mechanisms. While current clinical investigational drugs predominantly target antioxidant stress pathways, there remains an urgent need for multi-target therapeutic agents with enhanced therapeutic potential. Notably, RIPK1-mediated necroptosis and neuroinflammation have emerged as critical drivers of secondary brain injury, impacting stroke severity and clinical prognosis. Guided by these mechanistic insights, we rationally designed and synthesized a structurally diverse series of novel 4,5-dihydro-1H-pyrazole derivatives, followed by comprehensive biological evaluations. Compound <strong>23a</strong> demonstrated potent RIPK1 kinase inhibitory activity (IC₅₀ = 0.115 μM), and exhibited superior antioxidant efficacy (IC₅₀ = 9.72 μM) compared to the clinically approved drug edaravone (IC₅₀ = 22.79 μM). Furthermore, <strong>23a</strong> demonstrated remarkable anti-ferroptosis activity by suppressing PTGS2 mRNA expression (IC₅₀ = 0.156 μM). <em>In vivo</em> studies showed that <strong>23a</strong> markedly reduced cerebral infarction volume and improved neurological function scores in transient middle cerebral artery occlusion (tMCAO) model, outperforming edaravone, and demonstrated multi-target effects against oxidative stress, necroptosis, and ferroptosis in the ischemic penumbra tissue. These findings collectively highlight <strong>23a</strong> as a promising triple-target lead compound for ischemic stroke therapy, warranting further optimization and development.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"296 ","pages":"Article 117884"},"PeriodicalIF":6.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319617","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":"Unveiling ortho-phenolic Mannich ciprofloxacin-chalcone conjugates with potential antineoplastic activity: synthesis, mechanistic study, in silico docking and molecular dynamic simulation","authors":"Islam M. Abdel-Rahman ,&nbsp;Mohamed Abdel-Aziz ,&nbsp;Heba Ali Hassan ,&nbsp;Dalia H. Abu-Baih ,&nbsp;Mohamed badr ,&nbsp;Moustafa Fathy ,&nbsp;Ibrahim M. Salem ,&nbsp;Tarek S. Ibrahim ,&nbsp;Alaa M. Hayallah ,&nbsp;GamalEl-Din A. Abuo-Rahma","doi":"10.1016/j.ejmech.2025.117891","DOIUrl":"10.1016/j.ejmech.2025.117891","url":null,"abstract":"<div><div>A new series of ortho-phenolic Mannich ciprofloxacin-chalcone hybrids <strong>5a-j</strong> were synthesized and evaluated against the NCI-60 cancer cell lines, unveiling their promising potential as cytotoxic agents. Notably, compounds <strong>5a, 5d a</strong>nd <strong>5j</strong> exhibited notable anti-proliferative efficacy against both LOX IMVI and HCT 116 cell lines, indicating promising cytotoxic potential, with IC₅₀ = 2.53, 2.01, 17.36, 12.23 and 3.1 μM for HCT-116 cells, respectively and IC₅₀ = 0.73, 0.64, 3.32, 13.72 and 1.17 μM for leukemia SR cells, respectively. Mannich base <strong>5j</strong> achieved excellent inhibitory effect on Topo IIβ in both LOX IMVI and HCT-116 cell lines with inhibition value of 75.51 % and 76.39 %. Cell cycle analysis and expression analysis of Bax, Bcl2, P53 and P21 genes were performed on LOX IMVI and HCT-116 cell lines with compound <strong>5j</strong> and also on caspase 3 actifundation in HCT-116 and LOX- IMIV cell lines. The docking outcomes aligned with the biological screening revealed higher affinity of the most active compound <strong>5j</strong> against topoisomerase-I and topoisomerase-II biotargets, serving it as promising antineoplastic agent. Besides, using atomistic standard 100 ns dynamic simulation consideration, the stability of the formed complexes between compound <strong>5j</strong> and the topoisomerase-1 and topoisomerase-2 active sites was considered under dynamic behavior. Hence, Mannich base <strong>5j</strong> is considered a promising antineoplastic candidate that requires further <em>in vivo</em> investigation.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"296 ","pages":"Article 117891"},"PeriodicalIF":6.0,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329445","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 “Hypoxia-selective prodrug restrains tumor cells through triggering mitophagy and inducing apoptosis” [Europ. J. Med. Chem. 283 (2025) 17155]","authors":"Fangjie Wang, Lairong Song, Qianqian Xu, Ang Jia, Xiangwei Meng, Hongfei Jiang, Renshuai Zhang","doi":"10.1016/j.ejmech.2025.117881","DOIUrl":"https://doi.org/10.1016/j.ejmech.2025.117881","url":null,"abstract":"The authors regret &lt; that in Fig. 5E, the concentration label was incorrectly marked as “10 μM”. The correct concentration should be “5 μM”. Additionally, the same concentration label in the Graphical Abstract needs to be updated to reflect this change&gt;.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"16 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144329255","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":"Homoisoflavones: Structural diversity, pharmacological activities, and photocatalytic synthesis strategies - A comprehensive review","authors":"Juan Liu,&nbsp;Qi Zhang,&nbsp;Da-Le Guo,&nbsp;Mei-Mei Li,&nbsp;Yun Deng","doi":"10.1016/j.ejmech.2025.117864","DOIUrl":"10.1016/j.ejmech.2025.117864","url":null,"abstract":"<div><div>Homoisoflavones, a rare subclass of flavonoids distinguished from isoflavones by an additional carbon atom in their parent structure, have garnered attention for their significant pharmacological properties. Firstly, this review methodically analyzes the structural diversity of all documented homoisoflavone variants and their pharmacological activities, including antibacterial, antitumor, anti-inflammatory, and other biological effects, based on studies spanning from 1973 to the latest accessible data (March 2025). Secondly, the photo-induced synthesis methodologies for homoisoflavones are meticulously scrutinized and elaborated upon, compared with traditional synthetic approaches, as photo-mediated organic synthesis strategy continue to gain prominence as a valuable tool in medicinal chemistry. Finally, based on the structural features, pharmacological activities, and photo-induced synthesis strategies of homoisoflavones, potential future development prospects are proposed. For the first time, this article analyzes the medicinal chemistry potential of homoisoflavones from the perspective of photocatalysis, highlighting their structural features, pharmacological activities, and innovative synthesis strategies. It is hoped that this review will provide valuable guidance for the development of homoisoflavones in medicinal chemistry.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"296 ","pages":"Article 117864"},"PeriodicalIF":6.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144312196","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":"Discovery of a potential anti-ischemic stroke agent by suppressing ferroptosis through the ATF3/SLC7A11/GPX4 pathway","authors":"Xiangyi Kong ,&nbsp;Penghui Wei ,&nbsp;Liying Meng ,&nbsp;Zongjiang Yu ,&nbsp;Xuemeng Liu ,&nbsp;Mei Li ,&nbsp;Yanan Zou ,&nbsp;Jianjun Li ,&nbsp;Guanzhao Wu","doi":"10.1016/j.ejmech.2025.117873","DOIUrl":"10.1016/j.ejmech.2025.117873","url":null,"abstract":"<div><div>Ischemic stroke is a leading cause of morbidity and mortality worldwide. Despite its widespread impact, effective treatments remain limited. Idebenone (IDE) has shown promise in promoting recovery following stroke; however, its efficacy during the acute phase of ischemic stroke remains suboptimal. Therefore, the development of novel IDE analogs is of significant importance for improving outcomes in ischemic stroke treatment. Herein, we designed and synthesized a series of novel IDE analogs (<strong>1a</strong>–<strong>1g</strong>). An oxygen-glucose deprivation/reoxygenation (O/R) cell model and middle cerebral artery occlusion (MCAO) animal model were employed to investigate the effects of these drugs <em>in vitro</em> and <em>in vivo</em>, respectively. <strong>1c</strong> was identified as the most promising candidate owing to its potent neuroprotective effects. Experimental analyses demonstrated that treatment with <strong>1c</strong> reduced infarct size following ischemic injury and enhanced neuronal survival. <strong>1c</strong> further alleviated neurodegeneration following ischemia/reperfusion (I/R) injury by inhibiting ferroptosis. Furthermore, our findings revealed that the expression of activating transcription factor 3 (ATF3) was upregulated after I/R injury, but markedly suppressed upon treatment with <strong>1c</strong>. ATF3 overexpression downregulates the expression of SLC7A11 and GPX4, which are critical regulators of ferroptosis, thereby facilitating ferroptosis following I/R injury. Overall, our findings highlight the therapeutic potential of <strong>1c</strong> in ischemic stroke and provide insight into the underlying mechanisms of its neuroprotective effects.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"296 ","pages":"Article 117873"},"PeriodicalIF":6.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319619","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":"Recent advance of KRAS-G12C inhibitors for cancer therapy","authors":"Mengqi Li ,&nbsp;Huan Wang ,&nbsp;Fei Wang ,&nbsp;Dan Liu ,&nbsp;Chong Feng ,&nbsp;Guangxin Yan ,&nbsp;Xiaoxue Fan","doi":"10.1016/j.ejmech.2025.117878","DOIUrl":"10.1016/j.ejmech.2025.117878","url":null,"abstract":"<div><div>The RAS gene family encodes key oncoproteins that play a central role in cellular signal transduction and tumorigenesis. KRAS exhibits the highest mutation frequency in human cancers, accounting for approximately 80 % of RAS-driven malignancies, with the glycine-to-cysteine substitution at codon 12 (G12C) being one of the most prevalent oncogenic variants. RAS proteins regulate downstream signaling pathways by modulating transcription and translation processes, while at the cellular level, they promote malignant phenotypes such as uncontrolled proliferation and metastasis, making them critical therapeutic targets. In 2021, the FDA approved AMG510 (Sotorasib), the first covalent inhibitor targeting the KRAS-G12C mutation. Nevertheless, emerging resistance mechanisms necessitate continuous medicinal chemistry innovations. Currently, many highly KRAS-G12C inhibitors have been approved or are undergoing various clinical stages. This review provides an overview of contemporary medicinal chemistry approaches in KRAS-G12C inhibitor development. The collective insights from this analysis, combined with existing literature, provide valuable frameworks for designing novel KRAS-G12C targeted therapeutics.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"296 ","pages":"Article 117878"},"PeriodicalIF":6.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144312232","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":"Focal adhesion kinase inhibitors in fibrotic diseases therapy: Development and therapeutic potential","authors":"Cailing Gan ,&nbsp;Wei Wei ,&nbsp;Taixiong Xue ,&nbsp;Yuting Xie ,&nbsp;Lin Yue ,&nbsp;Xingping Su ,&nbsp;Yan Yu ,&nbsp;Zhihao Liu ,&nbsp;Tinghong Ye","doi":"10.1016/j.ejmech.2025.117882","DOIUrl":"10.1016/j.ejmech.2025.117882","url":null,"abstract":"<div><div>Organ fibrosis, characterized by dysregulated extracellular matrix deposition due to abnormal tissue repair, remains a significant challenge in medical research. Although nintedanib and pirfenidone have been approved for pulmonary fibrosis, effective treatments for hepatic, cardiac, and renal fibrosis remain markedly limited. The focal adhesion kinase (FAK) has been extensively implicated in the pathogenesis of organ fibrosis, with FAK kinase inhibition emerging as a pivotal therapeutic strategy for fibrosis modulation. In this review, we present a comprehensive analysis of FAK's biological functions in fibrotic progression and review preclinical advancements in FAK inhibitor development. We focus on the classification of FAK inhibitors, emphasizing their binding patterns, pharmacodynamic efficacy, and selectivity profiles from the perspective of pharmaceutical chemists. Additionally, we propose strategic frameworks for development of novel drugs targeting FAK for the treatment of fibrosis. The findings discussed in this review can guide the development of FAK inhibitors for treating organ fibrosis and underscore potential challenges in the drug development process.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"296 ","pages":"Article 117882"},"PeriodicalIF":6.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319618","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":"The role of quinoline in the development of near-infrared fluorescent probes for diagnosis of Alzheimer's disease","authors":"Lúcia Melo,&nbsp;Artur M.S. Silva,&nbsp;Hélio M.T. Albuquerque","doi":"10.1016/j.ejmech.2025.117874","DOIUrl":"10.1016/j.ejmech.2025.117874","url":null,"abstract":"<div><div>Alzheimer's disease (AD) is a common neurodegenerative disorder, having some negative impacts, affecting memory and other cognitive abilities, caused by injuries in brain cells. It is widely accepted that early diagnosis is essential for the successful management of AD. Since the current diagnosing strategies for imaging Aβ and tau proteins face limitations, near-infrared fluorescence (NIRF) has been pursued as alternative for <em>in vivo</em> applications. As described in recent dedicated literature, quinoline (and its analogues) is a valuable scaffold for creating new fluorescent probes due to its compact molecular size, the presence of a nitrogen atom in its ring which enhances coordination properties, and its capacity to form hydrogen bonds, as well as the easy chemical manipulation to tune several properties. In recent years, numerous fluorescent probes incorporating this moiety have been developed. This review focuses on the quinoline moiety as key component of several fluorescent probes, highlighting their design strategies, optical characteristics, and <em>in vitro</em> and <em>in vivo</em> performance, based on their distinct detection mode such as aggregation induced emission (AIE), intramolecular charge transfer (ICT) and twisted intramolecular charge transfer (TICT).</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"296 ","pages":"Article 117874"},"PeriodicalIF":6.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319621","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 a dual-action agent targeting bromodomain and extraterminal domain and H2S release for the treatment of hepatic and pulmonary injury","authors":"Yanghui Zhu ,&nbsp;Lian Wang ,&nbsp;Zhaoping Pan ,&nbsp;Mingxia Liu ,&nbsp;Fengbo Wu ,&nbsp;Xiang Wen ,&nbsp;Gu He","doi":"10.1016/j.ejmech.2025.117887","DOIUrl":"10.1016/j.ejmech.2025.117887","url":null,"abstract":"<div><div>Organ injury represents one of the leading causes of mortality worldwide, severely impacting patients' quality of life while imposing substantial economic and psychological burdens. Both hepatic and pulmonary injuries can trigger pro-inflammatory cascades, subsequently promoting fibrosis, cirrhosis, and ultimately organ failure. Organ fibrosis is characterized by excessive extracellular matrix deposition and is strongly associated with increased morbidity and mortality. In this study, we designed and synthesized a series of novel compounds based on JQ-1 and anethole trithione (ATT) that simultaneously release hydrogen sulfide (H₂S) and inhibit bromodomain and extraterminal domain proteins (BET), with the aim of attenuating liver and lung injuries. Among these compounds, <strong>11r</strong> demonstrated exceptional efficacy in H₂S release and significantly suppressed the CCl₄-induced upregulation of fibrosis markers (α-SMA and fibronectin), c-Myc, and CDC25B, while also reducing cellular apoptosis in LO2 hepatocytes. In a CCl₄-induced murine liver fibrosis model, daily oral administration of <strong>11r</strong> (30 mg/kg) for three consecutive days significantly improved hepatic function, restored damaged liver architecture, and reduced collagen deposition, exhibiting superior therapeutic efficacy compared to JQ-1 or ATT monotherapy. Furthermore, <strong>11r</strong> extended the survival duration of CCl₄-treated mice and mitigated systemic damage including spleen and lungs. Notably, <strong>11r</strong> also enhanced pulmonary function and diminished collagen accumulation in a bleomycin (BLM)-induced murine pulmonary fibrosis model. Our studies demonstrate that compound <strong>11r</strong> represents a promising therapeutic candidate for the treatment of hepatic and pulmonary fibrosis. This study not only highlights the potential synergistic benefits of combining BRD4 inhibition with H₂S donation for fibrotic disease management but also establishes a foundation for future clinical investigations and mechanistic studies to further elucidate the underlying pharmacological mechanisms.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"296 ","pages":"Article 117887"},"PeriodicalIF":6.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144312197","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":"Therapeutic targeting of ubiquitin-specific protease 7 (USP7): Mechanistic insights, dysregulation, and advances in drug discovery","authors":"Anwar A. El-Hamaky,&nbsp;Mervat H. El-Hamamsy,&nbsp;Tarek F. El-Moselhy,&nbsp;Nabaweya Sharafeldin,&nbsp;Haytham O. Tawfik","doi":"10.1016/j.ejmech.2025.117872","DOIUrl":"10.1016/j.ejmech.2025.117872","url":null,"abstract":"<div><div>The ubiquitin-proteasome system (UPS) is a crucial regulator of many proteins, tagging them with ubiquitin as a post-translational modification (PTM) to be identified by proteasome for degradation. The ubiquitination process utilizes a cascade of enzymes involving ubiquitin-activating enzymes (E1), ubiquitin-conjugating enzymes (E2), and ubiquitin-ligases (E3), to covalently attach ubiquitin with pervasive assembly possibilities, known as the ubiquitin code. As part of physiological homeostasis, ubiquitin is reversibly cleaved from proteins <em>via</em> deubiquitylating enzymes (DUBs) in a well-orchestrated process, altering the protein's fate. Among the DUBs, ubiquitin-specific protease 7 (USP7) is considered a pivotal member due to its role in regulating the stability of multiple proteins involved in various biological activities, including p53 stability, DNA damage response, transcription, epigenetics, immune response, and viral infection. However, overexpression of USP7 is involved in many tumors and viral infections, rendering USP7 a promising target for therapeutic intervention. This review provides a brief discussion of the USP7 structure, its biological functions, and its role in disease pathology. The development of USP7 inhibitors is systematically summarized, ranging from irreversible covalent inhibitors, such as thiophene, thiazole, and tetrahydroacridine derivatives, to FT827 and XL177A, to reversible non-covalent inhibitors, including derivatives of indeno[1,2-<em>b</em>]pyrazine, 2-aminopyridine, pyrimidinone, imidazopyridine, 7-pyridyl-2,3-dihydrobenzofuran, and tetrahydroquinoline bi-aryl. Also, natural products, USP7 degraders, and computational efforts were covered. Reported activities and SAR are highlighted to assist drug discovery scientists in rationalizing the subsequent generation of USP7 inhibitors.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"296 ","pages":"Article 117872"},"PeriodicalIF":6.0,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144312194","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}