European Journal of Medicinal Chemistry最新文献

{"title":"Discovery and exploration of disubstituted [1,2,5]oxadiazolo- [3,4-b]pyrazines as novel C-C chemokine receptor type 5 signaling inhibitors targeting the intracellular allosteric binding pocket","authors":"Margaux Billen ,&nbsp;Sten Reynders ,&nbsp;Sandra Claes ,&nbsp;Silke Kleinboelting ,&nbsp;Jef Rozenski ,&nbsp;Radu-George Bulai ,&nbsp;Edoardo Rocca ,&nbsp;Natalie Z.M. Homer ,&nbsp;Scott P. Webster ,&nbsp;Tim P. Kaminski ,&nbsp;Eveline Lescrinier ,&nbsp;Dominique Schols ,&nbsp;Peter Verwilst","doi":"10.1016/j.ejmech.2025.117600","DOIUrl":"10.1016/j.ejmech.2025.117600","url":null,"abstract":"<div><div>The C-C chemokine receptor type 5 is a G protein-coupled receptor expressed on various immune cells, playing a crucial role in inflammation and chemotaxis. Beyond its physiological functions, C-C chemokine receptor type 5 is implicated in numerous diseases, including cardiovascular, central nervous system, immune system, and infectious diseases, as well as in the progression of cancer. The therapeutic potential of C-C chemokine receptor type 5 inhibition has been demonstrated by antagonists targeting the extracellular domain, notably maraviroc, a Food and Drug Administration-approved Human Immunodeficiency Virus entry inhibitor. However, challenges such as suboptimal pharmacokinetics and efficacy necessitate new antagonists with unique modes of action. Recent advancements in G protein-coupled receptor structural characterization have identified a novel intracellular allosteric binding site in chemokine receptors. This study introduces a series of disubstituted [1,2,5]oxadiazolo-[3,4-<em>b</em>]pyrazines targeting the intracellular allosteric binding pocket of C-C chemokine receptor type 5. Among these, compound <strong>3ad</strong> emerged as a promising C-C chemokine receptor type 5-selective allosteric antagonist with an half-maximal inhibitory concentration of 1.09 μM and an almost 30-fold selectivity over C-C chemokine receptor type 2. Molecular dynamics simulations and a competition assay with a Gα_q11 mimetic were used to confirm the intracellular binding mode of these compounds. This novel class of C-C chemokine receptor type 5-selective intracellular antagonists offers a foundation for developing molecular tools and therapeutic agents, potentially overcoming the limitations of current extracellular C-C chemokine receptor type 5 antagonists.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"291 ","pages":"Article 117600"},"PeriodicalIF":6.0,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776196","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 potent focal adhesion kinase (FAK) inhibitor A8 with enhanced antitumor activity","authors":"Ye Li ,&nbsp;Yong He ,&nbsp;Chenyu Zhang ,&nbsp;Lu Gan ,&nbsp;Huabei Zhang","doi":"10.1016/j.ejmech.2025.117593","DOIUrl":"10.1016/j.ejmech.2025.117593","url":null,"abstract":"<div><div>FAK has emerged as a promising therapeutic target for cancer treatment due to its role in tumor survival, metastasis, and invasion. Herein, we report the rational design, synthesis, and comprehensive evaluation of a novel FAK inhibitor, compound <strong>A8</strong>. Our structure-activity relationship (SAR) studies identified <strong>A8</strong> as a potent FAK inhibitor, with an FAK-IC₅₀ value of 0.87 nM, superior to <strong>VS6063</strong> (1.49 nM). <em>In vitro</em> studies demonstrated that <strong>A8</strong> significantly suppressed tumor cell viability, cancer stem cell activity, and cell migration in A549 and SKOV-3 cell lines. Mechanistic insights were provided by surface plasmon resonance (SPR) analysis, revealing high-affinity binding of <strong>A8</strong> to FAK with a Kd value of 15 <em>μ</em>M. Radiolabeling studies with <strong>[¹⁸F]A8</strong> highlighted favorable tumor uptake and retention in S180 tumor-bearing mice. Notably, <strong>A8</strong> efficiently penetrated the blood-brain barrier, with brain uptake values reaching 2.63 ± 0.63 %ID/g at 15 min and 1.62 ± 0.77 %ID/g at 120 min. <em>In vivo</em> antitumor efficacy trials in A549 and SKOV-3 tumor models confirmed <strong>A8's</strong> robust activity, with tumor inhibition rates of 59.15 % and 57.9 %, respectively, surpassing <strong>VS6063</strong> and standard chemotherapeutics. Combination therapy with paclitaxel further enhanced <strong>A8's</strong> antitumor effects in SKOV-3 models. Acute toxicity studies indicated that <strong>A8</strong> was well-tolerated up to 2000 mg/kg in mice, with no observed acute toxicity. Molecular docking and dynamics simulations substantiated the stable binding of <strong>A8</strong> to the FAK protein. Collectively, our findings underscore the potential of compound <strong>A8</strong> as a lead candidate for FAK-targeted cancer therapeutics, warranting further preclinical and clinical investigations.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"291 ","pages":"Article 117593"},"PeriodicalIF":6.0,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782976","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 non-electrophilic TRPA1 channel agonists with anti-nociceptive effects via rapid current desensitization","authors":"Nan Yang ,&nbsp;Zhen Qiao ,&nbsp;Qiqi Zhou ,&nbsp;Xiuying Chang ,&nbsp;Chaoyue Sun ,&nbsp;Yanru Zhang ,&nbsp;Ningning Wei ,&nbsp;KeWei Wang","doi":"10.1016/j.ejmech.2025.117586","DOIUrl":"10.1016/j.ejmech.2025.117586","url":null,"abstract":"<div><div>Desensitizing transient receptor potential ankyrin 1 (TRPA1) cation channel through agonists emerges as an effective strategy for developing analgesics. Many TRPA1 agonists are electrophilic irritants, including BITC and iodoacetamide (IA), which covalently bind to cysteine residues in the cytoplasmic region of the channel. The electrophile JT010 is also recognized as a potent TRPA1 agonist <em>via</em> covalent modification of Cys621, whose irritant effects have been confirmed in humans, highlighting a commonly undesirable property of these electrophilic agonists. Cryo-electron microscopy (cryo-EM) structures have shown that these electrophiles induce a strong driving force for conformational change through electrophilic modification of TRPA1. However, the stable activated conformation induced by electrophiles might delay subsequent desensitization, leading to prolonged TRPA1-mediated nociception responses <em>in vivo</em>. Therefore, developing non-electrophilic TRPA1 agonists may mitigate the irritation associated with electrophilic agonists by accelerating the desensitizing process. To test this hypothesis, we designed and synthesized a series of novel TRPA1 agonists by removing the electrophilic functional group of JT010. Among these synthetic compounds, whole-cell patch clamp recording assays identified compound <strong>21</strong> as a selective TRPA1 agonist with an EC₅₀ of 25.47 ± 1.56 μM for <em>h</em>TRPA1, exhibiting faster desensitization (τ = 20.02 ± 1.66 s) of <em>m</em>TRPA1 compared to electrophiles JT010 (41.71 ± 4.10 s) and BITC (68.05 ± 5.57 s). Importantly, compound <strong>21</strong> demonstrated effective analgesic properties without irritation in mice. Our findings support the hypothesis that facilitating rapid desensitization of TRPA1 by non-electrophilic channel agonists enhances anti-nociceptive effects. Compound <strong>21</strong> may serve as a promising lead for further optimization.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"291 ","pages":"Article 117586"},"PeriodicalIF":6.0,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776199","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 adamantane scaffold: Beyond a lipophilic moiety","authors":"Chianna Dane,&nbsp;Andrew P. Montgomery,&nbsp;Michael Kassiou","doi":"10.1016/j.ejmech.2025.117592","DOIUrl":"10.1016/j.ejmech.2025.117592","url":null,"abstract":"<div><div>Adamantyl-based compounds have been successful clinically for the treatment of neurological disorders and viral infections. Whilst the effects of incorporating adamantane into a drug scaffold is contextual by nature, its unique structural and physicochemical properties have attracted considerable attention. Previous reviews have highlighted its ability to alter physicochemical properties such as lipophilicity. However, with the movement to incorporate structural complexity and escape the ‘flat land’ of modern drug discovery, adamantane provides value beyond a hydrophobic substituent. The non-planar three-dimensional rigid scaffold allows for the precise positioning of substituents to probe drug targets more effectively. This review evaluates the synthetic accessibility and subsequent integration of multi-substituted and hetero-adamantane containing ligands in drug discovery programs. The vast benefits of adamantyl-based motifs beyond increasing the lipophilicity of a target compound are discussed thus emphasising its multi-dimensional value in drug discovery.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"291 ","pages":"Article 117592"},"PeriodicalIF":6.0,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Towards new antibiotics: P. aeruginosa FabF ligands discovered by crystallographic fragment screening followed by hit expansion","authors":"Charis Georgiou ,&nbsp;Ludvik Olai Espeland ,&nbsp;Hemalatha Bukya ,&nbsp;Vladyslav Yadrykhins'ky ,&nbsp;Bengt Erik Haug ,&nbsp;Prathama S. Mainkar ,&nbsp;Ruth Brenk","doi":"10.1016/j.ejmech.2025.117563","DOIUrl":"10.1016/j.ejmech.2025.117563","url":null,"abstract":"<div><div>There is an urgent need for new antibiotics. FabF (3-oxoacyl-[acyl-carrier-protein] synthase 2), which catalyses the rate limiting condensation reaction in the fatty acid synthesis II pathway, is an attractive target. Very few inhibitors of FabF are known and most are derived from natural products. In an effort to further explore the chemical space of FabF ligands, we have carried out fragment screening by X-ray crystallography against an intermediated state-mimicking variant of <em>P. aeruginosa</em> FabF (<em>Pa</em>FabF C164Q). This screen has resulted in 48 hits out of which 16 bind in or close to the malonyl-CoA or fatty acid binding site or an adjacent dimer interface. None of the closer investigated fragments were active in a binding assay, but the same was the case for fragments derived from a potent FabF inhibitor. For hit optimization, we focused on the two fragments binding close to the catalytic residues of FabF. Different strategies were followed in the optimization process: exploration of commercially available analogues, fragment merging, virtual screening of a combinatorial make-on-demand space, and design and in-house synthesis of analogues. In total, more than 90 analogues of the hit compounds were explored, and for 10 of those co-crystal structures could be determined. The most potent ligand was discovered using manual structure-based design and has a binding affinity of 65 μM. This data package forms a strong foundation for the development of more potent and diverse FabF inhibitors.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"291 ","pages":"Article 117563"},"PeriodicalIF":6.0,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143776198","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 sodium–hydrogen exchanger 1 inhibitors with diphenyl ketone scaffold: Design, Synthesis, mechanism and evaluation in mice model of heart failure","authors":"Meng Cao ,&nbsp;Yating Guo ,&nbsp;Wenhua Tan ,&nbsp;Chunyu Feng ,&nbsp;Qingsong Chen ,&nbsp;Mengmeng Yao ,&nbsp;Jie Xu ,&nbsp;Zhuo Chen ,&nbsp;Qianbin Li","doi":"10.1016/j.ejmech.2025.117585","DOIUrl":"10.1016/j.ejmech.2025.117585","url":null,"abstract":"<div><div>Sodium-hydrogen exchanger 1 (NHE1) is a potential target for drug discovery of heart failure (HF). Cardioprotection effect of empagliflozin (EMPA) was reported to be related to binding with NHE1 protein. Herein, a series of NHE1 inhibitors bearing benzhydryl and diphenyl ketone skeleton were rationally designed and efficiently synthesized. Cell viability assay and pH recovery experiment based on H9c2 cells were conducted and compound <strong>7g</strong> was found to have equal NHE1 inhibitory activity to cariporide (0.64 μM) with the IC₅₀ values of 0.78 μM. <em>In vitro</em>, <strong>7g</strong> at 1 μM effectively rescued glucose deprivation (GD)-induced cellular damage by decreased overload of Ca²⁺ concentration and reactive oxygen species (ROS), improved mitochondrial dysfunction and autophagy. <em>In vivo</em>, compared with the clinically approved drug empagliflozin (30 mg/kg), <strong>7g</strong> alleviated left ventricular systolic dysfunction in a heart failure model induced by isoproterenol (ISO) at lower concentration (10 mg/kg). In summary, this study supplies a promising lead compound with novel scaffold for NHE1 inhibitor and also provide a feasible strategy for HF drug discovery.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"291 ","pages":"Article 117585"},"PeriodicalIF":6.0,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766994","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 sinomenine derivatives inhibiting macrophage polarization against rheumatoid arthritis through selectively targeting heme oxygenase-1","authors":"Yong-Zhe Zheng, Yao Kong, Fang-Fang Zhuo, Yue Shen, Yu-qi Wang, Zhuo Yang, Tao Wang, Si-Miao Yu, Ling Li, Ming Yu, Tian-Tian Wei, Dan Liu, Lu-Zheng Xu, Bo Han, Fen Liu, Zhengren Xu, Ke-Wu Zeng, Peng-Fei Tu","doi":"10.1016/j.ejmech.2025.117596","DOIUrl":"https://doi.org/10.1016/j.ejmech.2025.117596","url":null,"abstract":"Sinomenine (<strong>SIN</strong>) is clinically available for the treatment of rheumatoid arthritis (RA), but the side effects of <strong>SIN</strong> limit clinical applications. In this study, we designed and synthesized <strong>SIN</strong> derivatives that incorporated a novel ring fragment and assessed bioactivities in macrophages. Among the compounds, <strong>SIN 14</strong> exhibited significantly more potent inhibitory effects on inflammatory mediator production compared to the other derivatives, which induced macrophage polarization from M1 to M2 phenotype. Through thermal proteome profiling (TPP), we demonstrated that <strong>SIN 14</strong> specifically targeted heme oxygenase 1 (HO-1) and induced the activation through an allosteric mechanism. In particular, <strong>SIN 14</strong> exhibited the distal helix and the surface-exposed loop (CD-loop), which facilitates substrate binding and product release, ultimately leading to the liberation of anti-inflammatory metabolites. In vivo, <strong>SIN 14</strong> could inhibit RA-related inflammatory edema in collagen-induced arthritis (CIA) mice. Single-cell RNA transcriptome sequencing was employed to elucidate the cellular and transcriptional landscape in CIA mice after <strong>SIN 14</strong> treatment. These results indicated that <strong>SIN 14</strong> reduced the M1/M2 polarization ratio of macrophages, thereby alleviating the severity of inflammation in synovial tissues. Taken together, our study identifies <strong>SIN 14</strong> as a promising candidate for anti-RA drug discovery. Furthermore, we emphasize HO-1 as a distinctive cellular target for RA therapy.","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"216 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766954","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":"Enabling electrochemical, decarboxylative C(sp2)–C(sp3) cross-coupling for parallel medicinal chemistry","authors":"Jennifer Morvan ,&nbsp;Bingqing Tang ,&nbsp;Pavel Ryabchuk ,&nbsp;Evelien Renders ,&nbsp;Stefaan Last ,&nbsp;Lars Van Eynde ,&nbsp;Karolina Bartkowiak ,&nbsp;Peter J.J.A. Buijnsters ,&nbsp;Alexander X. Jones ,&nbsp;Mary-Ambre Carvalho ,&nbsp;Justin B. Diccianni","doi":"10.1016/j.ejmech.2025.117583","DOIUrl":"10.1016/j.ejmech.2025.117583","url":null,"abstract":"<div><div>Herein we report the development of an automated protocol for coupling aliphatic carboxylic acids and aryl halides under mild, electrochemical conditions. Carboxylic acids are one of the largest pools of commercially available building blocks utilized in parallel medicinal chemistry to expand structure-activity relationships. However, their usage in decarboxylative cross-coupling reactions to forge C(<em>sp</em>^<em>2</em>)–C(<em>sp</em>^<em>3</em>) bonds is low due to challenges associated with direct decarboxylation. Redox-active esters (RAE) are commonly employed to increase the reactivity of carboxylic acids for decarboxylative cross-coupling reactions. Previously, coupling reagent byproducts from in situ generated RAEs proved detrimental to transition metal catalysis. We have developed a purification-free protocol for activating carboxylic acids as <em>N</em>-hydroxyphthalimide (NHPI) esters, which are employed in electrochemical decarboxylative cross-coupling in a high-throughput, automated fashion. This automated workflow enables the preparation of compound libraries including PROTACs. By enabling the pool of commercial aliphatic carboxylic acids to be rapidly incorporated into drug-like molecules, this protocol can potentially impact how C(<em>sp</em>^<em>2</em>)–C(<em>sp</em>^<em>3</em>) cross-coupling reactions are performed in drug discovery campaigns.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"291 ","pages":"Article 117583"},"PeriodicalIF":6.0,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766993","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":"Effect of stereochemistry at position C20 on the antiproliferative activity and selectivity of N-acylated derivatives of salinomycin","authors":"Michał Antoszczak ,&nbsp;Julia Krzywik ,&nbsp;Greta Klejborowska ,&nbsp;Michał Sulik ,&nbsp;Szymon Sobczak ,&nbsp;Dominika Czerwonka ,&nbsp;Ewa Maj ,&nbsp;Małgorzata Ullrich ,&nbsp;Tomasz Sobierajski ,&nbsp;Jarosław Sukiennik ,&nbsp;Joanna Wietrzyk ,&nbsp;Witold Mozga ,&nbsp;Przemysław Pilaszek ,&nbsp;Adam Huczyński","doi":"10.1016/j.ejmech.2025.117598","DOIUrl":"10.1016/j.ejmech.2025.117598","url":null,"abstract":"<div><div>Salinomycin (<strong>SAL</strong>), a natural polyether ionophore, exhibits a broad spectrum of pharmacological activities, including potent anticancer activity. Over the past decade, much effort has been put into developing methods for rational chemical modification of <strong>SAL</strong> to obtain semisynthetic analogs with higher anticancer activity than the native structure. In this paper, we describe an optimized procedure for synthesizing C20-aminosalinomycin <strong>2</strong> with native stereochemistry at position C20, which was confirmed by single-crystal X-ray diffraction analysis. We further transformed amine precursor <strong>2</strong> into a series of 48 C20–<em>N</em>-(thio)acylated products, including <em>N</em>-(sulfon)amides, <em>N</em>-(thio)ureas, and <em>N</em>-carbamates (urethanes), along with their sulfur analogs, i.e., <em>S</em>-substituted thiocarbamates and dithiocarbamates. This previously unreported class of derivatives showed superior cytotoxicity mostly in the nano- and subnanomolar concentration range and improved selectivity toward human cancer cells compared to those of chemically unmodified <strong>SAL</strong> and a commonly used oncological drug cisplatin. Of note, the obtained products inhibited the proliferation of reference cancer cells more effectively than their C20-<em>epi</em>-<em>N</em>-acylated counterparts, pointing out the pivotal role of stereochemistry at position C20. Our findings support the premise that the modification of <strong>SAL</strong> is a fruitful strategy for products with promising biological activity profiles. Moreover, the straightforward protocols should be of significant value for more elaborate modifications of <strong>SAL</strong> in the future.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"291 ","pages":"Article 117598"},"PeriodicalIF":6.0,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766991","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":"Research progress of active compounds from traditional Chinese medicine in the treatment of stroke","authors":"Xinyi Yin ,&nbsp;Shutang Li ,&nbsp;Junwei Wang ,&nbsp;Meng Wang ,&nbsp;Jinfei Yang","doi":"10.1016/j.ejmech.2025.117599","DOIUrl":"10.1016/j.ejmech.2025.117599","url":null,"abstract":"<div><div>Stroke is a serious cerebrovascular disease that is categorized into two types: ischemic and hemorrhagic. The pathological mechanisms of ischemic stroke are complex and diverse, encompassing processes such as neuroinflammation and apoptosis. The pathological processes of hemorrhagic stroke primarily involve the disruption of the blood-brain barrier and cerebral edema. Western medical treatment methods show certain effectiveness during the acute phase of stroke, but they are limited by a narrow therapeutic window and secondary injuries. Traditional Chinese medicine (TCM) has a long history and unique advantages in treating stroke. Studies confirm that active compounds derived from TCM exert multi-pathway, multi-target effects, significantly improving therapeutic outcomes and reducing adverse reactions. However, due to the complexity of the components in TCM, research on monomeric components still faces challenges. This article reviews the relevant research progress published in domestic and international journals over the past twenty years regarding the mechanisms of action of monomeric components of TCM in the treatment of stroke, aiming to provide insights and references for the clinical application of TCM in stroke treatment and further new drug development.</div></div>","PeriodicalId":314,"journal":{"name":"European Journal of Medicinal Chemistry","volume":"291 ","pages":"Article 117599"},"PeriodicalIF":6.0,"publicationDate":"2025-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143766953","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}