Current medicinal chemistry最新文献

{"title":"Key Toxic Genes and Mechanisms of Di(2-ethylhexyl) Phthalate-Induced Non-Alcoholic Fatty Liver Disease: A Multi-Omics Study.","authors":"Xuemeng Zhao, Zhuoyu Gu, Jingya Yan","doi":"10.2174/0109298673439900260125080319","DOIUrl":"https://doi.org/10.2174/0109298673439900260125080319","url":null,"abstract":"<p><strong>Introduction: </strong>Non-alcoholic fatty liver disease (NAFLD) has emerged as the most prevalent chronic liver disease, with di(2-ethylhexyl) phthalate (DEHP) potentially exacerbating its progression. The toxicological mechanisms through which DEHP induces NAFLD remain elusive. This study aims to identify critical toxic genes involved in the development of DEHP-induced NAFLD.</p><p><strong>Methods: </strong>The carcinogenic potential of DEHP was predicted based on its Simplified Molecular Input Line Entry System (SMILES) notation. Biomarkers were identified through differential expression analysis, and a nomogram was constructed and validated. The functional roles of these biomarkers were explored through enrichment analysis, immune cell infiltration, molecular docking, and molecular dynamics simulations. Single- cell analysis pinpointed the key cellular players in the process.</p><p><strong>Results: </strong>The study identified activating transcription factor 3 (ATF3) and mitogen-activated protein kinase 8 (MAP3K8) as critical biomarkers. Pathways enriched by these biomarkers included \"electron transfer from variant/mutation-inactivated PINK1 to complex I\". Both ATF3 and MAP3K8 showed significant negative correlations with M2 macrophages and strong positive associations with activated mast cells. Binding affinities of ATF3 and MAP3K8 to DEHP were calculated at -5.9 kcal/mol and -7.7 kcal/mol. Hepatic stellate cells were ultimately identified as pivotal in the disease mechanism.</p><p><strong>Discussion: </strong>Compared to traditional research approaches, this study employs network toxicology and molecular docking techniques, integrating single-cell sequencing and spatial transcriptomics to provide a comprehensive framework for investigating the potential toxic effects of di(2-ethylhexyl) phthalate (DEHP) in non-alcoholic fatty liver disease (NAFLD).</p><p><strong>Conclusion: </strong>This study provides valuable insights into the molecular processes underlying DEHP-induced NAFLD.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147765166","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Significance of HBOT in Hypoxia-Induced Pathophysiological Conditions: A Comprehensive Investigative Study.","authors":"Rashi Bhargava, Kanchan Bhardwaj, Patrik Oleksak, Kamil Kuca","doi":"10.2174/0109298673341721260326075727","DOIUrl":"https://doi.org/10.2174/0109298673341721260326075727","url":null,"abstract":"<p><p>Hyperbaric oxygen therapy involves breathing pure oxygen at high pressure (around 2-2.5 atmospheres), leading to increased blood oxygen levels in tissues. The therapeutic efficacy of hyperbaric oxygen therapy (HBOT) is often dose-dependent, correlating with the number of applications, particularly within hypoxic tissues. HBOT provides neuroprotection following central nervous system trauma and serves as a critical intervention for non-neurological conditions, including Fournier's gangrene, chronic osteomyelitis, and carbon monoxide poisoning. It has also been applied as an adjunctive treatment in surgical site infections, radiation-induced tissue damage, and, more recently, in COVID-19-associated hypoxemia. HBOT enhances recovery in hypoxic and ischemic tissues; relative contraindications such as uncontrolled hypertension and untreated ulcers require careful consideration. Current applications of HBOT are guided by evidence- based protocols established by international and national hyperbaric medicine associations such as the Undersea and Hyperbaric Medical Society (UHMS) and the European Underwater and Baromedical Society (EUBS). In this review, we have discussed the properties of HBOT and explored in depth the physiological relevance of oxygen in the treatment of several disorders, based on clinical evidence, including current indications and underlying mechanisms. HBOT has demonstrated promising outcomes in neurological and neuropsychological disorders, with reports of improved neuronal activation, cognitive performance, and functional recovery in both acute and chronic disease patients. In clinical reports, HBOT was found to be effective in activating nerves and treating neuropsychological disorders in both non-chronic and chronic disease patients.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147671194","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Non-Coding RNAs and Common Neurosurgical Conditions: A Key to Future Personalized Molecular Therapy.","authors":"Ilgiz Gareev, Ozal Beylerli","doi":"10.2174/0109298673501096260403082528","DOIUrl":"https://doi.org/10.2174/0109298673501096260403082528","url":null,"abstract":"","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147671230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cold-Induced Gouty Arthritis: Exploring the Pathophysiological Link between Hyperuricemia and Gout Flare Triggers.","authors":"Zhijian Lin, Anjana Goel, Faiyazur Rahman Faizi, Mohsin Maqbool, Siying Chen, Krishan Kumar, Ayushi Sharma","doi":"10.2174/0109298673390853251016115256","DOIUrl":"https://doi.org/10.2174/0109298673390853251016115256","url":null,"abstract":"<p><p>Cold temperatures have been recognized as a possible catalyst for gouty arthritis exacerbations in individuals with hyperuricemia. The mechanisms underlying cold-induced gout are, however, minimally recognized. The article examines the pathophysiological connection between hyperuricemia and cold-induced gout flare triggers, emphasizing the molecular and physiological mechanisms involved. Genetic predisposition significantly influences an individual's risk of developing hyperuricemia and subsequent gout, underscoring the relevance of genetic variables in disease susceptibility. The diagnosis of gout depends on a combination of laboratory testing, such as blood uric acid levels, synovial fluid examination for urate crystals, and imaging to evaluate joint damage. Cold exposure is a significant environmental element that promotes the crystallization of monosodium urate in synovial fluid, initiating an inflammatory response. Activating the NLR family pyrin domain-containing 3 (NLRP3) inflammasome triggers the production of pro-inflammatory cytokines, consequently contributing to the pathophysiology of gout flares. The NLRP3 inflammatory system gets activated, leading to the secretion of pro-inflammatory cytokines. Low temperatures additionally impair blood circulation and the efficacy of immune cells, hence exacerbating inflammation. This review highlights the recent findings on epidemiology, pathophysiology, and diagnostic techniques of gouty arthritis, providing insights into prospective preventive strategies, therapies for those affected, and offering hope for the future. Overall, it provides an overview of the mechanisms behind cold-induced gout flares.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147671223","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Poly Beta-Amino Esters Nanoparticles as a Promising Strategy for Colon Cancer Therapy: Covering Synthesis Mechanisms, Characterization, Preclinical and Clinical Progress, and Regulatory Challenges.","authors":"Aakruti Shingare, Sankha Bhattacharya","doi":"10.2174/0109298673392295251112052529","DOIUrl":"https://doi.org/10.2174/0109298673392295251112052529","url":null,"abstract":"<p><p>Colon cancer is still one of the biggest health challenges globally, and most of the available treatments are hindered by drug resistance, systemic toxicity, and suboptimal efficacy. The Poly (beta-amino esters) (PBAE)-based nanoparticles have emerged as a promising nanotechnology-driven solution to these challenges. This review begins with the synthesis and functionalization of PBAE nanoparticles by focusing on polymerization techniques, targeting strategies, and scalability for clinical applications. The physicochemical properties of these nanoparticles, such as particle size, surface morphology, zeta potential, stability, biodegradability, and drug loading efficiency, are discussed in relation to their impact on therapeutic performance. Mechanistic insights into drug encapsulation, controlled release, tumour targeting, and the potential to overcome Multidrug Resistance (MDR) are also provided. Mechanistic insights are provided, including hydrophobic interaction-based drug encapsulation for efficient drug loading, pH-responsive controlled release in acidic tumor microenvironments, receptor-mediated tumour targeting using surface-functionalized ligands, and strategies to overcome Multidrug Resistance (MDR). Thereafter, preclinical studies are assessed, which include in-vitro cytotoxicity experiments and in-vivo animal models that test for efficacy, pharmacokinetics, and biodistribution. The review will then assess the status of PBAE nanoparticles in clinical trials, focusing on safety, efficacy, and the effects on patient outcomes in colorectal cancer treatment. Finally, regulatory approval, toxicity assessments, and commercialization challenges are discussed along with recommendations for overcoming these barriers. The review concludes by highlighting advancements in nanoparticle design, emerging therapeutic strategies, and the future potential of PBAE nanoparticles to transform colorectal cancer treatment.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147671207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Novel Indole Derivatives as SRC/EGFR Inhibitors: Synthesis, Biological Evaluation, and <i>In Silico</i> Analysis.","authors":"Sureyya Olgen, Banu Taktak Karaca, Sevde Nur Biltekin Kaleli, Ural U Demirel, Abdulilah Ece","doi":"10.2174/0109298673421543251205124008","DOIUrl":"https://doi.org/10.2174/0109298673421543251205124008","url":null,"abstract":"<p><strong>Introduction: </strong>Recent studies have reported a correlation between SRC and EGFR as key factors contributing to tumor aggressiveness in cancers, such as glioblastoma, colon, breast, and lung cancers. Resistance to therapy remains a major obstacle in cancer treatment. Therefore, the discovery of novel compounds with inhibitory potential is crucial. In this study, urea- and pyrimidine-containing compounds structurally similar to osimertinib were designed as potential inhibitors of both SRC and EGFR kinases, with the aim of identifying compounds that may also overcome resistance conferred by mutations.</p><p><strong>Methods: </strong>The compounds were synthesized through the development of new synthetic routes. Their structure-activity relationships (SAR) were evaluated using in vitro enzyme inhibition assays, cell culture experiments, molecular docking, and molecular dynamics studies.</p><p><strong>Results: </strong>Compounds 19, 20, and 21, which bear substitutions at the third position of the indole ring, inhibited SRC kinase with 77.75-89.22% activity. These compounds also demonstrated notable cytotoxicity against the PC3 cell line, with IC₅₀ values of 7.89, 6.92, and 9.85 μM, respectively, comparable to reference compounds cisplatin (IC₅₀ = 5.16 μM) and dasatinib (IC₅₀ = 0.9 μM). Notably, compound 20 was active against both EGFR and SRC kinases, with IC₅₀ values of 3.91 μM and 0.00058 μM, respectively. Compound 20 also exhibited the strongest cytotoxic effect on prostate cancer cells (IC₅₀ = 6.92 μM). Further analyses indicated that compound 20 induced apoptosis in cancer cells by increasing the levels of caspase-3, caspase-8, and Bax, while reducing Bcl-2 expression. Molecular docking and dynamics studies revealed strong interactions of compound 20 with the target receptors.</p><p><strong>Discussion: </strong>Docking and biological activity studies indicated that compound 20 (1-(2- Fluoro-4-methoxy-5-((4-(1-methyl-1H-indol-3-yl)pyrimidine-2-yl)amino)phenyl)-3- phenylurea) is a promising dual inhibitor of both EGFR and SRC kinases. <i>In silico</i> analyses further support the potential therapeutic efficacy of compound 20.</p><p><strong>Conclusion: </strong>Overall, compound 20 emerged as the most promising candidate from this study, warranting further investigation for its therapeutic potential.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147671256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of N-Glycolylneuraminic Acid and N-Acetylneuraminic Acid Glycans in Cancer Diagnosis and Therapeutic Strategies.","authors":"Sankha Bhattacharya, Khushi Gupta, Mayank Sharma, Dhrubojyoti Mukherjee, Bhupendra Prajapati","doi":"10.2174/0109298673384438251018113546","DOIUrl":"https://doi.org/10.2174/0109298673384438251018113546","url":null,"abstract":"<p><p>This review examines the function of N-glycolylneuraminic acid (Neu5Gc) and N-acetylneuraminic acid (Neu5Ac) glycans in cancer diagnosis and treatment, specifically in their interaction with biodegradable polymeric nanoparticles. Glycans play a central role in cellular communication, immune response, and adhesion, with structural changes usually indicative of precancerous conditions, thus making them key to diagnostic and therapeutic innovations. Neu5Gc, a dietary non-human sialic acid found in red meat and other foods, becomes a part of cell membranes, evoking immune reactions through anti-Neu5Gc antibodies that promote chronic inflammation, tumour formation, and metastasis. In contrast, Neu5Ac is compatible with human physiology and holds promise in antiviral and genetic disease therapies. This review explores the uses of biodegradable polymeric nanoparticles, including those from natural polymers such as chitosan and alginate, in Neu5Gc targeting for cancer diagnosis, immunotherapy, and drug delivery. It emphasizes their biocompatibility, controlled release, and improved targeting of Neu5Gc-containing tumour antigens. The review also addresses developments in electrochemical biosensors for Neu5Gc detection and computational glycan modeling, highlighting their potential in personalized oncology. By emphasizing biodegradable polymer-based approaches, this research highlights their promise as novel agents for cancer treatment, necessitating continued investigation into glycan-polymer interactions to further improve therapeutic outcomes.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147670579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting Clinical Outcomes and Immunotherapy Responses in Lung Adenocarcinoma Based on Nicotine Response Characteristics.","authors":"Haizhou Yue, Qianxin Zhou, Qinghua Xu, Shuyan Meng","doi":"10.2174/0109298673435756260219085341","DOIUrl":"https://doi.org/10.2174/0109298673435756260219085341","url":null,"abstract":"<p><strong>Introduction: </strong>Nicotine facilitates the progression of Lung Adenocarcinoma (LUAD) by activating signaling pathways and remodeling the Tumor Microenvironment (TME). However, the molecular classification based on nicotine response spectrum and its clinical relevance remained unclear.</p><p><strong>Materials and methods: </strong>We retrieved 52 nicotine response-related genes from the MSigDB database and analyzed RNA-seq data obtained from TCGA-LUAD and GSE31210 cohorts. Distinct molecular subtypes were identified by consensus clustering analysis. Next, differential gene expression analysis and functional enrichment analysis were conducted. A prognostic RiskScore model was constructed using LASSO and Cox regression, and validated via Kaplan-Meier and ROC analyses. Immune microenvironment features were assessed using CIBERSORT, ESTIMATE, and TIDE algorithms, while pathway associations were explored via GSEA.</p><p><strong>Results: </strong>Two distinct molecular subtypes (C1 and C2) were identified, with C1 showing a more favorable prognosis. A RiskScore model developed based on five genes (KCNK1, CPS1, ABCC2, TCN1, PGC) can effectively stratify patients into high- and low-risk groups, with the high-risk group exhibiting a worse overall survival (OS) (p < 0.001). The two risk groups demonstrated distinct enrichment of pathways. Notably, the low-risk group exhibited increased infiltration of regulatory T cells and M2 macrophages and lower TIDE scores, suggesting better immunotherapy response. A nomogram combining RiskScore and AJCC stage demonstrated strong predictive accuracy.</p><p><strong>Discussion: </strong>This study was the first to classify nicotine response-related molecular subtypes for LUAD, offering novel insights into nicotine-driven progression of LUAD. The RiskScore and nomogram may aid in risk stratification and personalized management, though further experimental validation is still needed.</p><p><strong>Conclusion: </strong>This study established a nicotine response-related prognostic model for LUAD, revealing its utility in predicting survival and immune therapy responses. Our findings provided novel biomarkers for personalized precision medicine in LUAD.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147671253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research Advances in the Structural Characterization and Biological Activity Assessment of Neocryptotanshinone.","authors":"Yingjie Wang, Jiaming Li, Sunliang Cui","doi":"10.2174/0109298673413967251201080735","DOIUrl":"https://doi.org/10.2174/0109298673413967251201080735","url":null,"abstract":"<p><p>Neocryptotanshinone (NCTS), a rare diterpene quinone bioactive compound isolated from Salvia miltiorrhiza, was first reported in 1941 and structurally characterized in 1987. The phenanthraquinone core has been extensively characterized in terms of structural confirmation and synthesis. Due to its low natural abundance, NCTS is challenging to extract but can be obtained through semisynthesis. Mechanistically, NCTS was identified in 2015 as an inhibitor of the nuclear factor kappa-B (NF-κB) pathway, inducing a cascade of downstream effects. Its low cytotoxicity, minimal induction of cyclooxygenase-2 (COX-2) expression, and other favorable pharmacological properties suggest therapeutic potential. Recent research has focused on NCTS's therapeutic applications. By modulating multiple pathways, it exerts beneficial effects on heart failure, myocardial ischemia/ reperfusion injury, cerebral ischemia, and type 2 diabetes mellitus. Pharmacokinetic studies are progressing; its promising bioavailability and absorption kinetics require validation. This review summarizes research progress on NCTS and its derivative 16-Ooleoylneocryptotanshinone, covering structural characterization, synthetic routes, structural modifications, pharmacological activities, traditional Chinese medicine applications, and pharmacokinetics. Our goal is to provide a reference for further development of NCTS, which remains in its nascent research phase.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147670612","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predicting Clinical Prognosis and Treatment Response in Glioblastoma Based on Gene Replication Stress-Related Features.","authors":"Qinghua Yuan, Weida Gao, Mian Guo","doi":"10.2174/0109298673423740260217112719","DOIUrl":"https://doi.org/10.2174/0109298673423740260217112719","url":null,"abstract":"<p><strong>Introduction: </strong>Glioblastoma (GBM) is a frequent malignant glioma among astrocytic tumors. Traditional pathological diagnostic criteria inadequately capture the underlying biological heterogeneity, highlighting the need for novel biomarkers to improve the diagnostic and prognostic accuracy of GBM.</p><p><strong>Methods: </strong>Based on the GBM-related data from The Cancer Genome Atlas (TCGA), Replication Stress-related Genes (RSGs) were collected. The RSG feature scores were calculated by ssGSEA and combined with WGCNA to screen target module genes. Enrichment analysis of the modular signature genes was conducted using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses. Prognostic genes were screened by univariate Cox and multivariate Cox regression analyses to establish a prognostic model for GBM. The Tumor Microenvironment (TME) was assessed using MCPcounter and TIMER methods. Immunotherapeutic responses and drug sensitivity responses were evaluated using the TIDE method. Finally, the role of PDCL3 in GBM was explored via immunohistochemistry, qRT-PCR, wound-healing, and transwell assays.</p><p><strong>Results: </strong>WGCNA identified RSG-associated module genes enriched in DNA replication, DNA-dependent ATPase activity, and other pathways. Four characterized genes (PDCL3, STEAP2, NXPH4, MPST) were selected to establish a Riskscore model for GBM. The risk score of the model was significantly related to the infiltration of myeloid dendritic cells, endothelial cells, and fibroblasts. The Riskscore was significantly positively correlated with the TIDE score, indicating higher immune escape potential in the high-risk group. The high-risk group was sensitive to Vinorelbine and Crizotinib. Through in vitro experiments, it was observed that knocking down PDCL3 noticeably inhibited the viability, migration, and invasion capacities of U87 cells.</p><p><strong>Discussion: </strong>This study validated the correlation between Oncogene-induced Replication Stress (ORS) characteristics and the prognosis of GBM, and screened RSGs to develop a Riskscore for GBM applying multiple types of regression analyses.</p><p><strong>Conclusion: </strong>We constructed and verified a four-gene ORS-based prognosis model for GBM, linking replication stress to immune evasion and drug sensitivity for the first time. Experimental validation confirmed the pro-tumorigenic role of PDCL3, offering potential biomarkers and therapeutic targets.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147670659","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}