European Journal of Medicinal Chemistry最新文献

{"title":"Repurposing FDA-approved drugs to target G-quadruplexes in breast cancer","authors":"Federica Moraca, Valentina Arciuolo, Simona Marzano, Fabiana Napolitano, Giuliano Castellano, Federica D’Aria, Anna Di Porzio, Laura Landolfi, Bruno Catalanotti, Antonio Randazzo, Bruno Pagano, Anna Maria Malfitano, Jussara Amato","doi":"10.1016/j.ejmech.2025.117245","DOIUrl":"https://doi.org/10.1016/j.ejmech.2025.117245","url":null,"abstract":"Breast cancer, a leading cause of cancer-related mortality in women, is characterized by genomic instability and aberrant gene expression, often influenced by noncanonical nucleic acid structures such as G-quadruplexes (G4s). These structures, commonly found in the promoter regions and 5’-untranslated RNA sequences of several oncogenes, play crucial roles in regulating transcription and translation. Stabilizing these G4 structures offers a promising therapeutic strategy for targeting key oncogenic pathways. In this study, we employed a drug repurposing approach to identify FDA-approved drugs capable of binding and stabilizing G4s in breast cancer-related genes. Using ligand-based virtual screening and biophysical methods, we identified several promising compounds, such as azelastine, belotecan, and irinotecan, as effective G4 binders, with significant antiproliferative effects in breast cancer cell lines. Notably, belotecan and irinotecan exhibited a synergistic mechanism, combining G4 stabilization with their established topoisomerase I inhibition activity to enhance cytotoxicity in cancer cells. Our findings support the therapeutic potential of G4 stabilization in breast cancer, validate drug repurposing as an efficient strategy to identify G4-targeting drugs, and highlight how combining G4 stabilization with other established drug activities may improve anticancer efficacy.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"21 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925209","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":"Functionalized regioisomers of the natural product phenazines myxin and iodinin as potent inhibitors of Mycobacterium tuberculosis and human acute myeloid leukemia cells","authors":"Goraksha Machhindra Khose, Siva Krishna Vagolu, Reidun Aesoy, Ísak Máni Stefánsson, Snorri Geir Ríkharðsson, Dagmar Ísleifsdóttir, Maonian Xu, Håvard Homberset, Tone Tønjum, Pål Rongved, Lars Herfindal, Elvar Örn Viktorsson","doi":"10.1016/j.ejmech.2025.117244","DOIUrl":"https://doi.org/10.1016/j.ejmech.2025.117244","url":null,"abstract":"The natural bioactive products myxin and iodinin are phenazine 5,10-dioxides possessing potent anti-bacterial and anti-cancer activity in vitro. This work describes the synthesis and derivatization of new myxin and iodinin regioisomers, developed from 1,3-dihydroxyphenazine 5,10-dioxide. Compounds were evaluated for activity towards <em>M. tuberculosis</em> (<em>Mtb</em>) strains, a human AML cell line (MOLM-13), and two non-cancerous mammalian cell lines (NRK and H9c2). Highly potent analogs were developed having IC₅₀ values against MTB down to 20 nM and 1.4 μM for human AML cells. 1-OH-3-<em>O</em>-alkyl substituted derivatives demonstrated high efficacy against <em>Mtb</em> and low toxicity in normal cells. 2,3-substituted regioisomers of myxin and iodinin were shown to be inactive, highlighting the importance of oxygen substituent in position 1 of the scaffold. A strong positive correlation between anti-MTB and anti-AML activity was revealed, suggesting a common mechanism of action in bacteria and cancer cells. These findings demonstrate the therapeutic potential of 1,3-<em>O</em>-functionalized phenazine 5,10-dioxides in chemotherapy for <em>Mtb</em> and AML and contribute to the structure-activity understanding of phenazine 5,10-dioxides with respect to their biological activity.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"14 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-01-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142925210","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":"Overview of the Epigenetic/Cytotoxic Dual-Target Inhibitors for Cancer Therapy","authors":"Hailiu Liang, Shuqing Li, Xiaopeng Peng, Hao Xiao","doi":"10.1016/j.ejmech.2024.117235","DOIUrl":"https://doi.org/10.1016/j.ejmech.2024.117235","url":null,"abstract":"Epigenetic dysregulation plays a pivotal role in the initiation and progression of various cancers, influencing critical processes such as tumor growth, invasion, migration, survival, apoptosis, and angiogenesis. Consequently, targeting epigenetic pathways has emerged as a promising strategy for anticancer drug discovery in recent years. However, the clinical efficacy of epigenetic inhibitors, such as HDAC inhibitors, has been limited, often accompanied by resistance. To overcome these challenges, innovative therapeutic approaches are required, including the combination of epigenetic inhibitors with cytotoxic agents or the design of dual-acting inhibitors that target both epigenetic and cytotoxic pathways. In this review, we provide a comprehensive overview of the structures, biological functions and inhibitors of epigenetic regulators (such as HDAC, LSD1, PARP, and BET) and cytotoxic targets (including tubulin and topoisomerase). Furthermore, we discuss recent advancement of combination therapies and dual-target inhibitors that target both epigenetic and cytotoxic pathways, with a particular focus on recent advances, including rational drug design, pharmacodynamics, pharmacokinetics, and clinical applications.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"159 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924473","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 proteolytically stable monocyte locomotion inhibitory factor peptide through systematic structural optimization","authors":"Yajing Ji, Yuan Gao, Xiang Li, Honggang Hu, Yuefan Zhang, Yejiao Shi","doi":"10.1016/j.ejmech.2025.117237","DOIUrl":"https://doi.org/10.1016/j.ejmech.2025.117237","url":null,"abstract":"The identification of novel molecular candidates capable of treating osteoarthritis (OA) has significant clinical implications. Monocyte locomotion inhibitory factor peptide (MLIF) is a pentapeptide derived from <em>Entamoeba histolytica</em>. It has been found possesses selective anti-inflammatory effects both <em>in vitro</em> and <em>in vivo</em>. Nonetheless, like many peptide therapeutics, MLIF has relatively poor proteolytic stability and short half-life <em>in vivo</em>, hindering its effective clinical applicability. To overcome these limitations, structural optimizations are needed to enhance the stability of MLIF while preserving or even enhancing its anti-inflammatory activities. Herein, a series of MLIF derivatives were designed and synthesized based on diverse structural modifications including <em>N</em>-terminal modifications, _D-amino acid replacement, <em>N</em>-methylation, sulfhydryl modification, cyclization, and splicing strategy. Among all the MLIF derivatives, MLIF 30 with replacing _L-methionine (Met) with _D-Met and linking the polyethylene glycol (PEG) to cysteine (Cys) of MLIF displayed enhanced <em>in vitro</em> anti-inflammatory activities. Further <em>in vivo</em> experiment demonstrated MLIF 30 could reduce cartilage inflammation and attenuate cartilage damage more effectively in the collagenase induced osteoarthritis (CIOA) mice due to its improved serum stability compared to the linear MLIF. These findings laid foundation for the development of potent and stable anti-inflammatory peptide therapeutics and pushed the frontier of MLIF for clinical OA treatment.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"122 9 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142917487","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":"Targeting JNK3 for Alzheimer's Disease: Design and Synthesis of Novel Inhibitors with Aryl Group Diversity utilizing Wide Pocket","authors":"Hyejin Kim, Haebeen Park, Joonhong Jun, Jihyun Moon, Jooyoung Oh, Swapnil P. Bhujbal, Jung-Mi Hah","doi":"10.1016/j.ejmech.2024.117209","DOIUrl":"https://doi.org/10.1016/j.ejmech.2024.117209","url":null,"abstract":"JNK3, a brain-specific stress-activated protein kinase, plays a critical role in Alzheimer's disease pathogenesis through phosphorylation of Tau and APP. This study aimed to develop selective JNK3 inhibitors based on a pyrazole scaffold, focusing on (<em>E</em>)-1-(2-aminopyrimidin-4-yl)-4-styryl-1<em>H</em>-pyrazole-3-carboxamide derivatives. Through systematic structural modifications and extensive SAR analysis, we identified compounds <strong>24a</strong> and <strong>26a</strong> as highly potent JNK3 inhibitors, with IC₅₀ values of 12 and 19 nM, respectively. Especially, <strong>24a</strong> revealed its potent and selective inhibition of JNK3, coupled with inhibition of the GSK3α/β kinases involved in Tau phosphorylation. <em>In vitro</em> studies revealed significant neuroprotective effects against Aβ_1-42-induced toxicity in primary neuronal cells and western blot analyses confirmed the compounds' ability to mitigate Aβ_1-42-induced c-Jun and APP phosphorylation, suggesting a multi-faceted approach to neuroprotection. Docking studies validated the retention of optimal interactions within the JNK3 binding pocket. Importantly, BBB PAMPA assays and ADME predictions indicated favorable blood-brain barrier permeability and pharmacokinetic profiles for the lead compounds. These findings represent a significant advancement in the development of selective JNK3 inhibitors, providing a strong foundation for further preclinical development of potential Alzheimer's disease therapeutics.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"6 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142924571","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 1H-indole-3-carbonitrile derivatives as potent TRK Inhibitors","authors":"Shaoshan Xu, Xiaosheng Jiang, Mengdi Xu, Chengjian Ai, Guanyi Zhao, Tao Jiang, Yang Liu, Zhen Tian, Meihui Zhang, Jinhua Dong","doi":"10.1016/j.ejmech.2024.117231","DOIUrl":"https://doi.org/10.1016/j.ejmech.2024.117231","url":null,"abstract":"Tropomyosin receptor kinase (TRK) has emerged as a promising therapeutic target in cancers driven by <em>NTRK</em> gene fusions. Herein, we report a highly potent TRK inhibitor, <strong>C11</strong>, developed using bioisosteric replacement and computer-aided drug design (CADD) strategies. Compound <strong>C11</strong> demonstrated significant antiproliferative effects against TRK-dependent cell lines (Km-12), and exhibited a dose-dependent inhibition of both colony formation and cell migration. Mechanistic study revealed that <strong>C11</strong> induced cancer cell death by arresting the cell cycle, triggering apoptosis, and reducing phosphorylated TRK levels. <em>In vitro</em> stability assays showed that compound <strong>C11</strong> possessed excellent plasma stability (t_1/2 &gt; 480 min) and moderate liver microsomal stability (t_1/2 = 38.9 min). Pharmacokinetic evaluation further indicated an oral bioavailability of 15.2% for compound <strong>C11.</strong> These results highlight compound <strong>C11</strong> as a promising lead compound for the further development of TRK inhibitors.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"34 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142917488","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 Potent and Orally Bioavailable FGFRs Inhibitor for Fibrotic Treatment","authors":"Lin Yue, Zui Tan, Wei Wei, Hongyao Liu, Taixiong Xue, Xingping Su, Xiuli Wu, Yuting Xie, Peilin Li, Doudou Wang, Zhihao Liu, Cailing Gan, Tinghong Ye","doi":"10.1016/j.ejmech.2024.117232","DOIUrl":"https://doi.org/10.1016/j.ejmech.2024.117232","url":null,"abstract":"Organ fibrosis, such as lung fibrosis and liver fibrosis, is a progressive and fatal disease. Fibroblast growth factor receptors (FGFRs) play an important role in the development and progression of fibrosis. Through scaffold hopping, bioisosteric replacement design, and structure-activity relationship optimization, we developed a series of highly potent FGFRs inhibitors, and the indazole-containing candidate compound <strong>A16</strong> showed potent kinase activity comparable to that of <strong>AZD4547</strong>. In addition, <strong>A16</strong> effectively suppressed the activation of lung fibroblasts and hepatic stellate cells (HSCs) induced by TGF-β1, leading to a reduction in collagen deposition. Notably, <strong>A16</strong> exhibited potent anti-fibrotic effects through the inhibition of the FGFR pathway <em>in vitro</em>. Compound <strong>A16</strong> also showed reasonable pharmacokinetic properties (<em>F</em> = 21.84%) and favorable cardiac safety (hERG IC₅₀ &gt; 20 μM). Moreover, in models of pulmonary fibrosis, <strong>A16</strong> ameliorated (in the prevention model) and reversed (in the treatment model) bleomycin-induced lung fibrosis, as well as mitigated inflammatory immune response in the lung. Furthermore, in the CCl₄-induced liver fibrosis model, when <strong>A16</strong> was administrated orally at a dose of 30 mg/kg/day for 3 weeks, it effectively improved liver function, restored damaged liver structures, and reduced collagen deposition. Taken together, these results suggest that <strong>A16</strong> could be a potential drug candidate for the treatment of organ fibrosis.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"26 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911571","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":"Functional and Structural Polypharmacology of Indazole-based Privileged Ligands to Tackle the Undruggability of Membrane Transporters","authors":"Katja Stefan, Sachin Puri, Muhammad Rafehi, Ganesh Latambale, Maria Neif, Franziska Tägl, Nike Sophia Arlt, Zeinab Nezafat Yazdi, Éva Bakos, Xiang Chen, Bohan Zhang, Wouroud Ismail Al-Khalil, Hauke Busch, Zhe-Sheng Chen, Csilla Özvegy-Laczka, Vigneshwaran Namasivayam, Kapil Juvale, Sven Marcel Stefan","doi":"10.1016/j.ejmech.2024.117234","DOIUrl":"https://doi.org/10.1016/j.ejmech.2024.117234","url":null,"abstract":"Despite the significant roles of solute carrier (SLC) and ATP-binding cassette (ABC) transporters in human health and disease, most remain poorly characterized as intrinsic and/or xenobiotic ligands are unknown, rendering them as ‘undruggable’. Polypharmacology, defined as the simultaneous engagement of multiple targets by a single ligand, offers a promising avenue for discovering novel lead compounds addressing these emerging pharmacological challenges – a major focus in contemporary medicinal chemistry. While common structural motifs among phylogenetically diverse proteins have been proposed to underlie polypharmacology through the concept of 'multitarget binding sites', a comprehensive analysis of these functional and structural aspects from a medicinal chemistry perspective has yet to be undertaken. In our study, we synthesized 65 distinct indazole derivatives and evaluated their activity across a broad biological assessment platform encompassing 17 specific and polyspecific SLC and ABC transporters. Notably, ten indazole compounds exhibited cross-target activity against challenging transporter targets associated with neurodegeneration (ABCA1), metabolic reprogramming (MCT4), and cancer multidrug resistance (ABCC10). One lead molecule demonstrated exceptional potency against these assessed targets. Furthermore, molecular blind docking experiments and advanced binding site analyses revealed, for the first time, conserved binding motifs across MCTs, organic anion transporting polypeptides (OATPs), organic cation transporters (OCTs), and ABC transporters, characterized by specific and recurring residues of tyrosine, phenylalanine, serine, and threonine. These findings highlight not only the potential of polypharmacology in drug discovery but also provide insights into the structural underpinnings of ligand binding across membrane transporters.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"93 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142911574","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":"Synthesis and biological evaluation of novel pyrrolo[2,3-b]pyridine derivatives as potent GSK-3β inhibitors for treating Alzheimer’s disease","authors":"Qing-Qing Xun, Jing Zhang, Yan-Peng Li, Ying Li, Yu-Ying Ma, Zhao-Bin Chen, Le-Ping Ding, Xiao-Long Shi","doi":"10.1016/j.ejmech.2025.117236","DOIUrl":"https://doi.org/10.1016/j.ejmech.2025.117236","url":null,"abstract":"The development of potent glycogen synthase kinase-3β (GSK-3β) inhibitor has been increasingly recognized as the candidate treatment against the multifactorial pathogenic mechanism of Alzheimer’s disease (AD). This study prepared various new pyrrolo[2,3-<em>b</em>]pyridine derivatives, evaluated the anti-AD activities and detected the security based on the structure-guided rational design. Our results indicated that many pyrrolo[2,3-<em>b</em>]pyridine derivatives had strong GSK-3β inhibitory activities, particularly compounds <strong>41</strong>, <strong>46</strong> and <strong>54</strong>, with the half maximal inhibitory concentrations (IC₅₀) of 0.22, 0.26 and 0.24 nM, respectively, and each of them generally possessed GSK-3β selectivity over 24 structurally similar kinases. In addition, further targeting studies at the cellular level revealed that compound <strong>41</strong> increased GSK-3β phosphorylation at Ser9 site dose-dependently for inhibiting GSK-3β activity, therefore inhibiting the hyperphosphorylation of tau protein by decreasing the p-tau-Ser396 abundance. Moreover, <strong>41</strong> up-regulated β-catenin and neurogenesis-related markers (GAP43 and MAP-2), thereby promoting neurite outgrowth of neurons in SH-SY5Y cells. According to the <em>in vitro</em> cells assay, <strong>41</strong> showed the lower cytotoxicity to SH-SY5Y cells with a survival rate of over 70% at the concentration of 100 μM. <em>In vivo</em> efficacy and acute toxicity experiments showed that, <strong>41</strong> effectively ameliorated the dyskinesia in AlCl₃-induced zebrafish AD models and exhibited its low‐toxicity nature in C57BL/6 mice. Overall, the pyrrolo[2,3-<em>b</em>]pyridine derivative <strong>41</strong> could serve as a promising GSK-3β inhibitor for treating AD.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"82 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142917786","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 new inhibitors of nuclease MRE11","authors":"Fedor Nikulenkov, Benoit Carbain, Raktim Biswas, Stepan Havel, Jana Prochazkova, Alexandra Sisakova, Magdalena Zacpalova, Melita Chavdarova, Victoria Marini, Vit Vsiansky, Veronika Weisova, Kristina Slavikova, Dhanraj Biradar, Prashant Khirsariya, Marco Vitek, David Sedlak, Petr Bartunek, Lukas Daniel, Jan Brezovsky, Jiri Damborsky, Lumir Krejci","doi":"10.1016/j.ejmech.2024.117226","DOIUrl":"https://doi.org/10.1016/j.ejmech.2024.117226","url":null,"abstract":"MRE11 nuclease is a central player in signaling and processing DNA damage, and in resolving stalled replication forks. Here, we describe the identification and characterization of new MRE11 inhibitors <strong>MU147</strong> and <strong>MU1409</strong>. Both compounds inhibit MRE11 nuclease more specifically and effectively than the relatively weak state-of-the-art inhibitor mirin. They also abrogate double-strand break repair mechanisms that rely on MRE11 nuclease activity, without impairing ATM activation. Inhibition of MRE11 also impairs nascent strand degradation of stalled replication forks and selectively affects BRCA2-deficient cells. Herein, we illustrate that our newly discovered compounds <strong>MU147</strong> and <strong>MU1409</strong> can be used as chemical probes to further explore the biological role of MRE11 and support the potential clinical relevance of pharmacological inhibition of this nuclease.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"29 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908660","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}