Chemical Biology & Drug Design最新文献

{"title":"Molecular Mechanisms and Efficacy of Tislelizumab, a PD-1 Inhibitor Developed in China, in Non-Small Cell Lung Cancer","authors":"Yihao Liu,&nbsp;Wenjun Meng,&nbsp;Lu Pan,&nbsp;Haoling Zhang,&nbsp;Qinqin He","doi":"10.1111/cbdd.70252","DOIUrl":"10.1111/cbdd.70252","url":null,"abstract":"<div>\u0000 \u0000 <p>Lung cancer remains the leading cause of cancer incidence and mortality worldwide, with non-small cell lung cancer (NSCLC) accounting for approximately 85% of all lung cancer cases. Tislelizumab, a PD-1 inhibitor developed in China, has shown promising efficacy as a monotherapy and in combination with chemotherapy. This study examines the molecular structure of tislelizumab and its interaction with PD-1, along with its therapeutic effects and adverse reactions in NSCLC patients. Using GRAMM (Global Range Molecular Matching), protein–protein docking was conducted to analyze the binding affinity of tislelizumab with PD-1. A comprehensive search in PubMed, Embase, Cochrane Library, and Web of Science identified eligible studies, including randomized controlled trials (RCTs) and single-arm studies reporting survival outcomes, tumor responses, or adverse events. Tislelizumab significantly improved event-free survival (RR = 1.40, 95% CI: 1.19–1.65) and median progression-free survival (mPFS) by 1.77 months in RCTs, and reduced the risk of disease progression or death by 41% (HR = 0.59, 95% CI: 0.52–0.67). The overall survival risk was reduced by 35% (HR = 0.65, 95% CI: 0.59–0.73). The overall response rate (ORR) was higher in the tislelizumab group (RR = 1.86). In single-arm studies, the 1-year overall survival rate was 73.8%, with an ORR of 59.5%. AEs were generally manageable, with more frequent elevated ALT/AST, hypothyroidism, and rash, but fewer cases of anemia and neutropenia compared to chemotherapy. Tislelizumab significantly improves survival outcomes and tumor response rates in NSCLC patients, with an overall acceptable safety profile. For patients with suboptimal responses, dose adjustments or combination strategies may help improve efficacy.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"107 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146148211","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":"Thiazole- and 1,3,4-Thiadiazole-Based Hybrids: Synthesis and In Vitro Cytotoxicity Against Human Cancer Cell Lines","authors":"Emine Terzi,&nbsp;Tuba Ozdemir Sanci,&nbsp;Beyza Ecem Oz Bedir,&nbsp;Elif Ercan,&nbsp;Emine Rana Bağcı,&nbsp;Ulviye Acar Çevik,&nbsp;Ecem Kaya Sezginer","doi":"10.1111/cbdd.70246","DOIUrl":"10.1111/cbdd.70246","url":null,"abstract":"<p>Problems such as high toxicity, low selectivity, and drug resistance encountered in cancer treatment increase the need for more effective and safe anticancer agents. In this study, the anticancer effects of new compounds consisting of thiazole and 1,3,4-thiadiazole derivatives were investigated. Compound <b>6e</b>, which showed the strongest cytotoxic effect, was evaluated in detail in human bladder (HTB-9) and lung (A549) cancer cells. According to the WST-1 test results, the IC₅₀ value of compound <b>6e</b> was determined as 38.9 μM for HTB-9 cells and 82.86 μM for A549 cells. As a result of Annexin V-FITC/PI double staining and flow cytometry analysis, it was determined that compound <b>6e</b> application significantly increased the apoptotic cell rates in both HTB-9 and A549 cells. It was observed that it significantly induced early apoptosis in HTB-9 cells and late apoptosis in A549 cells (<i>p</i> &lt; 0.0001). Caspase-3/7 activity was significantly increased in HTB-9 cells after compound <b>6e</b> application compared to the control group and similarly increased in A549 cells (<i>p</i> &lt; 0.0001). In cell cycle analyses, compound <b>6e</b> caused cell cycle arrest in the G2/M phase in HTB-9 and A549 cells. In the wound healing test, the migration speed in HTB-9 and A549 cells treated with compound <b>6e</b> after 24 h was significantly decreased (<i>p</i> &lt; 0.0001). Molecular docking revealed strong binding to caspase-3 (PDB ID: 1NMQ, score: −8.2 kcal/mol), identifying key interactions that mechanistically support its pro-apoptotic effects. In addition, the low cytotoxicity of compound <b>6e</b> in healthy BEAS-2B cells suggests that it has a selective anticancer effect.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"107 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146136880","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":"Targeting the Autophagy–Apoptosis Axis in Osteosarcoma: Therapeutic Potential of Biocompounds: A Review","authors":"Oznur Bayraktar Ekmekcigil,&nbsp;Secil Eroglu,&nbsp;Shiv Bharadwaj,&nbsp;Ammad Ahmad Farooqi,&nbsp;Devrim Gozuacik,&nbsp;Ozlem Kutlu","doi":"10.1111/cbdd.70257","DOIUrl":"10.1111/cbdd.70257","url":null,"abstract":"<div>\u0000 \u0000 <p>Osteosarcoma is a prevalent form of cancer that develops in growing bones. The precise cause of this multifaceted disease remains uncertain. Yet, genetic, genomic and proteomic research has enhanced our understanding of the disruption in its molecular signaling pathways. In this review, we attempted to highlight the regulation of autophagy pathways by a range of biocompounds (chemical compounds of biological origin) in osteosarcoma. Autophagy is a degradation mechanism, maintaining cellular homeostasis under basal and stress conditions. However, the role of autophagy is variable in cancer. There is a delicate balance between autophagy and apoptosis, and disruption of this balance is one of the causes of tumor formation and development. Autophagy and apoptosis can reciprocally activate or inhibit each other. Thus, autophagy works synergistically or antagonistically with apoptosis. In osteosarcoma, different biocompounds involve in the regulation of autophagy and/or apoptosis, triggering cellular signaling pathways, convenient or inconvenient for growth, proliferation, invasion and metastasis of cancer cells in a tumor. Also, some of the biocompounds have been shown to affect the therapeutic response of osteosarcoma cells. Therefore, biocompounds are promising candidates for the regulation of autophagy and may play critical roles in the crosstalk between autophagy and apoptosis in osteosarcoma.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"107 2","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146130154","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":"Prediction of Breast Cancer Lymph Node Metastasis by a Nomogram Model Integrating Pathomics, Radiomics, and Immunoscore","authors":"Tian Xu,&nbsp;Jingyao Feng,&nbsp;Kun Zhang,&nbsp;Liugang Gao,&nbsp;Jianlin Wang","doi":"10.1111/cbdd.70244","DOIUrl":"10.1111/cbdd.70244","url":null,"abstract":"<div>\u0000 \u0000 <p>This study aimed to develop a noninvasive nomogram that integrates deep learning-pathomics, radiomics, and immunoscore to predict lymph node metastasis (LNM) in breast cancer. Pathological features from 1133 TCGA-BRCA slides were extracted via ResNet50 and Lasso. Radiomics features from 137 MRI images (TCIA) were analyzed using pyradiomics. Immunoscore was calculated via ESTIMATE. A nomogram was constructed and validated with 10-fold cross-validation. The pathomics model achieved an AUC of 0.65 (95% CI: 0.61–0.68), sensitivity 0.62, specificity 0.67; radiomics 0.61 (95% CI: 0.50–0.72), sensitivity 0.59, specificity 0.63; and the combined nomogram 0.69 (95% CI: 0.59–0.79), sensitivity 0.66, specificity 0.71. Radiomics score was the strongest predictor. The nomogram provides a reliable noninvasive tool for predicting lymph node involvement, potentially reducing unnecessary biopsies.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"107 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146013225","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":"Tetramethylpyrazine Targets HDAC6-Mediated PINK1 Degradation to Alleviate Chronic Intermittent Hypoxia-Induced Injury in Human Bronchial Epithelial Cells (16HBE)","authors":"Yanjie Chen,&nbsp;Hongye Chen,&nbsp;Zhixiong Huang,&nbsp;Mulan Deng,&nbsp;Xin Zheng,&nbsp;Qihui Chen","doi":"10.1111/cbdd.70236","DOIUrl":"10.1111/cbdd.70236","url":null,"abstract":"<div>\u0000 \u0000 <p>Obstructive sleep apnea (OSA) is characterized by recurrent chronic intermittent hypoxia (CIH), which induces oxidative stress, inflammatory responses, and mitochondrial damage in bronchial epithelial cells. Tetramethylpyrazine (TMP) has been shown to exert lung-protective effects in other pathological models, but its role in mitigating CIH-induced 16HBE cell injury and the underlying molecular mechanisms have not been previously investigated. PTEN-induced putative kinase 1 (PINK1)-mediated mitophagy is a critical endogenous mechanism that defends against CIH-induced epithelial damage. However, whether TMP alleviates CIH-induced injury by regulating the PINK1 pathway remains unknown. CIH significantly reduced 16HBE cell viability, increased apoptosis rate, elevated inflammatory responses (IL-6 and TNF-α levels upregulated), and oxidative stress (ROS and MDA levels increased), and inhibited mitophagy (reduced PINK1 and LC3-II/LC3-I ratio, increased p62). TMP treatment improved cell viability in a dose-dependent manner; notably, 20 μg/mL TMP reversed CIH-induced apoptosis, inflammation, and oxidative stress, accompanied by upregulated PINK1 and restored mitophagy. Moreover, <i>HDAC6</i> knockdown mimicked TMP's benefits (enhanced PINK1 and mitophagy, reduced injury), while concurrent <i>PINK1</i> silencing reversed this effect. TMP protected 16HBE cells from CIH-induced injury by inhibiting HDAC6-mediated PINK1 deacetylation. This mechanism stabilized PINK1 protein, enhanced mitophagy, and thereby suppressed apoptosis, oxidative stress, and inflammation, identifying the HDAC6/PINK1 axis as a key regulatory pathway in CIH-induced cell injury.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"107 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145999098","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":"Daucosterol Targets PFKFB3 to Mitigates Sepsis-Induced Acute Lung Injury by Inhibiting Glycolysis and M1 Macrophage Polarization","authors":"Lulu Wang,&nbsp;Jingmin Zhou,&nbsp;Chuanfu Sun,&nbsp;Yuan Liu,&nbsp;Yingzhi Wang,&nbsp;Xianjin Zhang","doi":"10.1111/cbdd.70243","DOIUrl":"10.1111/cbdd.70243","url":null,"abstract":"<div>\u0000 \u0000 <p>Acute lung injury (ALI) is a severe inflammatory condition often triggered by infections. Glycolysis and macrophage polarization play critical roles in ALI pathogenesis. This study investigates the effects of Daucosterol on lipopolysaccharide (LPS)-stimulated lung injury and its potential mechanisms. In this research, BEAS-2B lung epithelial cells and MH-S alveolar macrophages were exposed to LPS and various concentrations of Daucosterol. Cell viability was assessed using CCK-8 assay. Glycolytic activity was evaluated by detecting ATP production, lactate level, and extracellular acidification rate. Macrophage polarization was assessed using flow cytometry. Tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels were detected by enzyme-linked immunosorbent assay. Gene expression was evaluated by reverse transcription-quantitative polymerase chain reaction and western blotting. A cecal ligation and puncture (CLP)-induced ALI mouse model was used to validate the protective effect of Daucosterol in vivo. Results showed that Daucosterol prevented the reduction in cell viability in LPS-stimulated BEAS-2B cells. In MH-S macrophages, Daucosterol inhibited LPS-induced glycolysis and M1 polarization while promoting M2 polarization. Mechanistically, Daucosterol reversed the LPS-induced upregulation of PFKFB3. Overexpression of PFKFB3 counteracted the inhibitory effects of Daucosterol on glycolysis and M1 polarization. In vivo, Daucosterol significantly alleviated CLP-induced ALI by improving lung histopathology, reducing pulmonary edema, enhancing oxygenation, inhibiting myeloperoxidase and caspase-3 activity, and decreasing TNF-α and IL-6 levels in bronchoalveolar lavage fluid. In conclusion, Daucosterol targets PFKFB3 to mitigate sepsis-induced ALI by inhibiting glycolysis and M1 macrophage polarization, offering a potential therapeutic strategy for ALI.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"107 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146000190","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":"Network Pharmacology-Based Analysis and In Vitro Experiments Validation Reveal Tormentic Acid Induces Apoptosis via PI3K/AKT/HSP90 Pathway in HepG2 Cells","authors":"Jingyang Lu,&nbsp;Yue Qiu,&nbsp;Facheng Bai,&nbsp;Lijun Pang,&nbsp;Junjie Tan,&nbsp;Jun Deng,&nbsp;Yeting Lin,&nbsp;Jinbin Wei,&nbsp;Dandan Wang","doi":"10.1111/cbdd.70239","DOIUrl":"10.1111/cbdd.70239","url":null,"abstract":"<div>\u0000 \u0000 <p>Tormentic acid (TA) has demonstrated potential anti-hepatocellular carcinoma (HCC) effects. This study aimed to explore the anti-HCC effect and underlying mechanisms of TA via network pharmacology, molecular docking, molecular dynamics simulation and in vitro experiments. In this study, HCC-related genes were obtained from the GeneCards OMIM, and GEO databases. The targets of TA were collected from Swiss Target Prediction, TargetNet, and the PharmMapper database. A protein–protein interaction network of TA anti-HCC target genes was constructed using the STRING database and visualized by Cytoscape. The potential anti-HCC targets of TA were then identified through GO and KEGG pathway enrichment analyses using the DAVID database. Molecular docking and molecular dynamics simulation were performed to evaluate the binding affinity and structural stability of TA-target complexes. For the in vitro experiments, the CCK-8 assay was employed to assess the effects of TA on HepG2 cell viability. Apoptosis in HepG2 cells was detected via flow cytometry. Western blotting was used to elucidate the underlying molecular mechanisms of TA. Integrating network pharmacology and bioinformatics analyses revealed that the anti-HCC effect of TA was closely associated with apoptosis and the PI3K/AKT/HSP90 pathway. Molecular docking and molecular dynamics simulation demonstrated that TA-target protein complexes maintained marked structural stability and exhibited favorable kinetic properties. In vitro experiments showed that TA significantly inhibited the proliferation of HepG2 cells and induced apoptosis. Western blot results further indicated that TA treatment increased the expression of Bax while decreasing the expression levels of PI3K, AKT, HSP90, and Bcl-2. TA suppressed the proliferation of HepG2 cells and induced apoptosis, possibly by regulating the PI3K/AKT/HSP90 signaling pathway.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"107 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145992267","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":"Design, Synthesis, and Anticancer Assessment of Benzylated Pyrrole-Based Pyrido[2,3-d]Pyrimidines as Thymidylate Synthase Inhibitors","authors":"Adarsh Kumar,&nbsp;Sonu Rajput,&nbsp;Ankit Kumar Singh,&nbsp;Vineet Prajapati,&nbsp;Amita Verma,&nbsp;Prateek Pathak,&nbsp;Umashanker Navik,&nbsp;Jurica Novak,&nbsp;Pradeep Kumar","doi":"10.1111/cbdd.70240","DOIUrl":"10.1111/cbdd.70240","url":null,"abstract":"<div>\u0000 \u0000 <p>Globally, colorectal cancer (CRC) is the second most common cause of cancer-related deaths and the third most common cancer. Thymidylate synthase (TS), a key enzyme involved in DNA biosynthesis, has emerged as a promising molecular target for anticancer therapy. In the present study, we designed and synthesized a series of 22 benzylated pyrrole-based pyrido[2,3-<i>d</i>]pyrimidines using Claisen Schmidt and Michael addition reactions, and evaluated their anticancer potential against four human cancer cell lines: HCT 116 (colorectal), A549 (lung), MCF-7 (breast), and MDA-MB-231 (triple-negative breast cancer) as well as for TS inhibitory potential. Compounds 1c and 2i exhibited potent TS inhibition with IC₅₀ values of 11.50 ± 1.08 nM and 17.12 ± 0.91 nM, respectively, comparable to the standard drug raltitrexed (IC₅₀ = 12.51 ± 0.91 nM). Molecular docking studies revealed stronger binding affinities of these compounds compared to raltitrexed, involving key interactions with the catalytic residue Cys195 of TS. Additionally, compounds 1c and 2i exhibited good stability in 300 ns molecular dynamics simulations along with acceptable drug-like properties and oral bioavailability. These findings suggest that compounds 1c and 2i are promising lead candidates for the development of TS inhibitors.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"107 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145992218","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":"EIF2AK2 Globally Binds and Regulates the Expression and Alternative Splicing of T2D-Related Genes in INS1 Cell","authors":"Lili Ning,&nbsp;Tong Liu,&nbsp;Yuanyuan Lv,&nbsp;Yan Cheng,&nbsp;Maoguang Yang,&nbsp;Hanqing Cai","doi":"10.1111/cbdd.70242","DOIUrl":"10.1111/cbdd.70242","url":null,"abstract":"<div>\u0000 \u0000 <p>This study aimed to investigate the impact of the RNA-binding protein eukaryotic translation initiation factor 2-alpha kinase 2 (EIF2AK2) gene, also known as PKR, on the condition of islet beta cells. In this study, EIF2AK2 was overexpressed in INS1 cells, and transcriptome data following EIF2AK2 overexpression were obtained using RNA-seq technology. Additionally, potential target genes that bind to EIF2AK2 were identified through iRIP-seq technology. The proteins interacting with EIF2AK2 were characterized using co-immunoprecipitation (CO-IP) combined with mass spectrometry to elucidate the molecular regulatory mechanisms of EIF2AK2 in INS1 cells. RNA-seq results indicated that in INS1 cells overexpressing EIF2AK2, 1171 genes were differentially expressed, and 2161 alternative splicing events were significantly altered. iRIP-seq data demonstrated that reads from the immunoprecipitated samples were significantly enriched in the intronic and coding sequence (CDS) regions. EIF2AK2 preferentially binds to the GCGGCGG motif in RNA. Comprehensive analysis suggests that EIF2AK2 may directly bind to and regulate the expression of Dusp8, Btg1, and Prkce, thereby affecting pancreatic islet cell functions. Furthermore, EIF2AK2 may influence islet cell function by modulating the alternative splicing of Zfr and Pias2. Additionally, combined with Co-IP mass spectrometry data, it was discovered that EIF2AK2 can interact with 649 proteins, including various differentially expressed RNA-binding proteins, transcription factors, and histones, which may be associated with diabetes. Our results indicate that EIF2AK2 may regulate the expression or alternative splicing of mRNA related to type 2 diabetes through direct or indirect binding. Additionally, it may influence the progression of type 2 diabetes by interacting with other proteins. We propose that EIF2AK2 plays a significant role in diabetic islet beta cells, and its aberrant regulatory pattern is closely associated with the onset and progression of type 2 diabetes.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"107 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145967872","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":"Exploring the Therapeutic Potential of Oridonin in the Treatment of Laryngeal Cancer: A Comprehensive Strategy Involving Network Pharmacology, Molecular Docking, Dynamic Simulation, and Experimental Verification","authors":"Rui Zhang,&nbsp;Lei Ren,&nbsp;Jiabin Hou,&nbsp;Chun Yang,&nbsp;Yang Sun,&nbsp;Fei Sun,&nbsp;Bo Yue","doi":"10.1111/cbdd.70222","DOIUrl":"10.1111/cbdd.70222","url":null,"abstract":"<div>\u0000 \u0000 <p>Laryngeal cancer (LC) is one of the most common malignant tumors of the head and neck, with high morbidity and mortality rates worldwide. Oridonin (Ori), a natural tetracyclic diterpenoid, exhibits notable anti-tumor properties. However, its efficacy and underlying mechanism in LC remain to be elucidated. This study employed comprehensive network pharmacology, molecular docking, and molecular dynamic simulation to investigate the molecular targets and mechanisms underlying the anti-LC effects of Ori, followed by in vitro validation of its key mechanisms. A total of 172 potential therapeutic targets of Ori for LC were identified. GO and KEGG analyses indicated that Ori's anti-LC mechanism primarily involved the PI3K-Akt, Ras, MAPK, and Rap1 signaling pathways. The PPI network and molecular docking analyses revealed that AKT1, EGFR, and MAPK1 are potential core targets of Ori. Additionally, molecular dynamics simulations and bioinformatics analyses further confirmed that these proteins are key candidate targets. In vitro, Ori inhibited the proliferation of LC Hep-2 and TU212 cells, induced apoptosis, arrested the cell cycle at the G1 phase, and suppressed migration and invasion. WB assays further showed that Ori significantly downregulated p-AKT expression in the PI3K/AKT pathway. These findings indicate that Ori represents a promising therapeutic candidate for LC.</p>\u0000 </div>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":"107 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2026-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145954390","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}