Current medicinal chemistry最新文献

{"title":"Beneficial Role of Zinc in Metabolic Syndrome: Understanding the Underlying Pathophysiological Mechanisms.","authors":"Abdullah Al Lawati, Emir Ličina, Patrycja Głoćko, Shaymaa Salah Abdelnaeim Hefny, Donia Elnemr, Ahmed Al Maskari, Srijit Das","doi":"10.2174/0109298673370733250807110441","DOIUrl":"https://doi.org/10.2174/0109298673370733250807110441","url":null,"abstract":"<p><p>Metabolic syndrome (MetS) is a complex disorder that comprises metabolic abnormalities such as central obesity, insulin resistance, dyslipidemia, and hypertension. Eventually, MetS leads to type 2 diabetes (T2DM) and increases the risk of other cardiovascular diseases. Patients with MetS are approximately five times more prone to develop T2DM. The increase in global prevalence of MetS is a major cause of concern. The microelement zinc is an essential trace element that plays a pivotal role in numerous biological processes occurring in the body. We carried out a thorough search of published studies in Scopus, PubMed, and Google Scholar databases. Zinc plays an important role in the functioning of the immune system, wound healing, protein synthesis, metabolism, inflammation, and different oxidative stress pathways. It is also vital for insulin homeostasis and signaling. The potential role of zinc in managing insulin resistance may be a key component in the treatment of MetS. Zinc acts via various signaling pathways, such as AMPK and mTOR, and influences lipid and glucose metabolism. The regulation of zinc metabolism at the cellular level is important for various biological processes, and disruption in zinc homeostasis results in the development of many diseases. The present review aims to discuss the role of zinc in MetS. It is concluded that zinc level modulation may be a key point in the prevention and treatment of MetS.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946020","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":"PREFACE.","authors":"Atta-Ur Rahman","doi":"10.2174/0109298673439579250825104543","DOIUrl":"https://doi.org/10.2174/0109298673439579250825104543","url":null,"abstract":"","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945984","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":"Expression, Prognostic Value, and Biological Function of CENPM in Colon Adenocarcinoma.","authors":"Zhiming Cai, Zhenrong Yang, Qian Yu, Tao Lin, Xincheng Su, Lv Lin, Yongjian Zhou","doi":"10.2174/0109298673387182250716075120","DOIUrl":"https://doi.org/10.2174/0109298673387182250716075120","url":null,"abstract":"<p><strong>Introduction: </strong>Centromere protein M (CENPM), a member of the CENP family, is correlated with several malignancies, but its role in colon adenocarcinoma (COAD) is unclear. This study aims to explore the expression, prognostic significance, and biological role of CENPM in COAD.</p><p><strong>Methods: </strong>The association of CENPM with the occurrence and progression of COAD was thoroughly analyzed via several bioinformatics databases. Furthermore, the correlation between CENPM expression and clinicopathological features and prognostic value was validated via immunohistochemistry (IHC) of tissue microarrays (TMAs) from 80 patients.</p><p><strong>Results: </strong>CENPM mRNA expression was significantly elevated in COAD samples compared with healthy tissues. As COAD progressed, CENPM expression decreased, and patients with lower CENPM transcript levels had a worse prognosis. IHC results further confirmed the overexpression of CENPM in COAD patients, identifying this gene as an independent prognostic factor. Additionally, high CENPM expression was linked to methylation in COAD patients, and the primary function of CENPM and its neighboring genes was determined to be cell cycle regulation. Immunological analysis demonstrated that CENPM expression was positively correlated with activated CD8+ T cells, CD4+ T cells, and dendritic cells (DCs) but negatively correlated with regulatory T cells (Tregs). CENPM expression was positively correlated with that of the immune checkpoint genes LAG3, CD244, LGALS9, PDCD1 (PD1), and PVRL2 but negatively correlated with the expression of BTLA, CSF1R, KDR, IL10RB, PDCD1LG2, and TGFBR1.</p><p><strong>Conclusion: </strong>CENPM is an independent prognostic factor for COAD, with its overexpression associated with improved survival. It regulates the cell cycle and tumor microenvironment, making it a promising potential predictive biomarker for immune therapy response.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144945982","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":"\"Next-in-class\" GLP-1R Danuglipron- and Lotiglipron-like Agonists: A Patent Review (2020-2024).","authors":"Elena V Tolkacheva, Alexandr Yu Saliev, Tagir L Salakhov, Konstantin V Balakin, Roman A Ivanov, Vladimir V Chernyshov","doi":"10.2174/0109298673366258250710101146","DOIUrl":"https://doi.org/10.2174/0109298673366258250710101146","url":null,"abstract":"<p><strong>Background: </strong>GLP-1 receptor peptide agonists have revolutionized type 2 diabetes mellitus and obesity treatment, primarily through injection-based therapies. Small-molecule GLP-1 receptor agonists allow oral administration, but none are clinically established. Pfizer's danuglipron and lotiglipron, presented in 2018-2019, were \"first-in-class\" drug candidates, becoming prototypes for \"next-in-class\" drug development.</p><p><strong>Objective: </strong>This review summarizes \"next-in-class\" GLP-1 receptor agonists developed, identifying different relationships between the molecular structure and functional activity of agonists.</p><p><strong>Methods: </strong>Patents containing danuglipron- and lotiglipron-like agonists from January 2021 to July 2024 were browsed in databases, such as Espacenet and Google Patents, using specified keywords. Over 5,000 compounds from 67 patent publications were analyzed.</p><p><strong>Results: </strong>Our analysis identified some key general SAR trends. The presence of a carboxyl group leads to highly active agonists, but replacing it with bioisosteric analogs may improve the ADME profile of the target compounds. The introduction of specific privileged fragments, as well as the replacement of 1H-benzo[d]imidazole nucleus or (S)-oxetan-2-ylmethyl substituent in the prototype structure with bioisosteric heterocycles, may be viable approaches. The replacement of 1,4-disubstituted piperidine linked with its (S)-2-methyl-substituted homologue or O, N-disubstituted piperidin-4-ol may also result in highly potent agonists. Additionally, the classic 2,4-EWG-disubstituted benzyl alcohol residue allows significant variability.</p><p><strong>Conclusion: </strong>Despite the limited clinical success of danuglipron and lotiglipron, as well as the inherent problems associated with the complex nature of GLP-1R signaling, the current state of research and the abundance of novel, promising chemotypes of highly potent compounds suggest that approved GLP-1R agonists may emerge in the coming years.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946063","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":"Expression of TCEAL2 is a Novel Prognostic Biomarker and Potential Therapeutic Target in Cervical Squamous Cell Carcinoma and Endocervical Adenocarcinoma.","authors":"Jinyuan Li, Zhen Ye, Yuhong Gan, Dongbing Li, Yibiao Chen","doi":"10.2174/0109298673371499250714133701","DOIUrl":"https://doi.org/10.2174/0109298673371499250714133701","url":null,"abstract":"<p><strong>Background: </strong>Cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) are major gynecological malignancies, causing significant cancer-related deaths in women. Current treatments yield poor outcomes, with a 5-year survival rate of only 17%. Identifying new biomarkers and therapeutic targets is crucial for improving prognosis and guiding personalized treatments.</p><p><strong>Methods: </strong>We analyzed TCEAL2 expression using data from The Cancer Genome Atlas (TCGA) across various cancers, including CESC. We explored its correlation with clinical features, prognosis, immune infiltration, MSI, mRNAsi, and drug sensitivity. TCEAL2 expression was validated in GSE9750 datasets and CESC cell lines using qRT-PCR.</p><p><strong>Results: </strong>TCEAL2 expression was significantly dysregulated in CESC. Elevated TCEAL2 levels correlated with poor clinical outcomes, including advanced pathological M stage (p = 0.009), initial treatment failure (p = 0.0098), and reduced overall survival (OS) (p = 0.013). TCEAL2 was an independent predictor of unfavorable OS (p = 0.032). It was associated with key pathways such as calcium signaling, oxidative phosphorylation, and Wnt signaling. TCEAL2 also correlated with immune cell infiltration, MSI, and mRNAsi. Notably, TCEAL2 levels inversely correlated with sensitivity to several drugs, including CAY10603 and SB-223133.</p><p><strong>Discussion: </strong>The results suggest that TCEAL2 plays a significant role in CESC progression and its tumor microenvironment. Its correlation with immune infiltration and drug sensitivity highlights its potential as a prognostic biomarker and therapeutic target. Future studies should focus on elucidating the molecular mechanisms and validating their clinical utility.</p><p><strong>Conclusion: </strong>TCEAL2 is a potential prognostic biomarker and therapeutic target in CESC. Further research is needed to explore its role and clinical applications.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946054","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":"Transcriptome-wide Association Studies Integrating Four Levels Identify Novel Targets for Idiopathic Pulmonary Fibrosis.","authors":"Jiaxin Shi, Linyou Zhang","doi":"10.2174/0109298673364730250721151447","DOIUrl":"https://doi.org/10.2174/0109298673364730250721151447","url":null,"abstract":"<p><strong>Introduction: </strong>Idiopathic pulmonary fibrosis (IPF) is a kind of interstitial lung disease with a poor prognosis. Even though genome-wide association studies (GWAS) have identified numerous loci linked to IPF risk, the underlying causal genes and biological processes are still mostly unknown.</p><p><strong>Methods: </strong>The IPF GWAS summary data included 4,125 cases, 20,464 controls from five cohorts. The weight file and related files for transcriptome association studies (TWAS) of plasma protein, multi-tissues, cross-tissue, and single-cell were obtained from Zhang's study, Mancuso lab, GTExV8 database, and Thompson's study, respectively. We conducted TWAS employing functional Summary-based Imputation (FUSION) from four levels, which were plasma protein, multiple tissues, cross-tissue, and single cell. Conditional and joint (COJO) analysis and multi-marker analysis of genomic annotation (MAGMA) analysis were used to validate the above results. Summary-data-based Mendelian randomization (SMR) and Bayesian co-localization analysis were utilized to explain the causal association between selected genes and the risk of IPF.</p><p><strong>Results: </strong>A total of 12, 361, 1187, and 72 genes were calculated from the four dimensions of TWAS. TOLLIP, GCHFR, ZNF318 TALDO1, CD151, and AP4M1 were selected by intersecting the results of the four sets of genes. GCHFR, TALDO1, CD151, and AP4M1 were verified by COJO analysis and MAGMA analysis. SMR and colocalization analyses identified GCHFR as the most significant gene for IPF.</p><p><strong>Discussion: </strong>We have applied the TWAS approach to identify novel therapeutic targets for IPF in multiple dimensions. Further biological testing will be required in future studies to validate our findings.</p><p><strong>Conclusion: </strong>In summary, we carried out an extensive TWAS that integrated four dimensions: plasma protein, multiple tissues, cross-tissue, and single cell. GCHFR was identified as the most significant gene for IPF in this study.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946018","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":"Decoding PRTFDC1's Role in Lung Adenocarcinoma: From Gene Expression to Clinical Implications.","authors":"Jian Yao, Qiang Zhang, Chunhe Zhong, Haiyang Zhang, Xinchi Lei, Dongbing Li","doi":"10.2174/0109298673367449250728104846","DOIUrl":"https://doi.org/10.2174/0109298673367449250728104846","url":null,"abstract":"<p><strong>Introduction: </strong>This study aims to elucidate the role of Phosphoribosyl Transferase Domain Containing 1 (PRTFDC1) in Lung Adenocarcinoma (LUAD) through bioinformatics analysis and experimental validation, exploring its potential as a biomarker for prognosis and treatment response.</p><p><strong>Methods: </strong>We analyzed PRTFDC1 gene expression patterns in 539 LUAD and 59 normal lung tissue samples from The Cancer Genome Atlas (TCGA). Using bioinformatics tools, we examined the correlation between PRTFDC1 expression and clinical characteristics, immune infiltration, Tumor Mutation Burden (TMB), and drug responsiveness. Experimental validation was conducted in LUAD cell lines (A549 and HCC-78) through the overexpression of PRTFDC1, followed by cell proliferation and cell cycle assays.</p><p><strong>Results: </strong>PRTFDC1 expression was significantly elevated in LUAD compared to normal tissues, correlating with poorer Progression-Free Survival (PFS) and Disease-Specific Survival (DSS). PRTFDC1 was associated with immune cell infiltration, TMB, and mRNA stemness index (mRNAsi). Overexpression of PRTFDC1 in LUAD cell lines promoted cell proliferation and cell cycle progression, mediated by Threonine Tyrosine Kinase (TTK).</p><p><strong>Discussion: </strong>The findings suggest that PRTFDC1 may serve as an independent prognostic marker for LUAD, influencing tumor progression and immune response. The correlation with TTK indicates a potential mechanism for PRTFDC1's impact on cell proliferation. However, further research is needed to validate these findings in larger cohorts and explore the underlying molecular mechanisms.</p><p><strong>Conclusion: </strong>PRTFDC1 is a promising biomarker for LUAD prognosis and treatment response, with potential implications for targeted therapies and personalized medicine.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946005","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":"Selenium Enhances Osteogenic Differentiation and Mineralization in Human Osteoblasts: Implications for Bone Health and Metabolism.","authors":"Erhan Sahin, Mahmoud Arafat, Ayse Tansu Koparal","doi":"10.2174/0109298673391434250430053916","DOIUrl":"https://doi.org/10.2174/0109298673391434250430053916","url":null,"abstract":"<p><strong>Introduction: </strong>Sodium Selenite (NaSe) is a molecule with various biological activities. Bone fractures and osteoporotic diseases are increasingly common health issues, prompting the search for alternative treatments. Therefore, the purpose of this study was to examine the antioxidant and osteogenic properties of NaSe.</p><p><strong>Methods: </strong>The experiments were conducted using the hFOB1.19 osteoblast cell line. The MTT assay was used to assess the effects of NaSe on cell viability, while cytotoxicity was evaluated with Lactate Dehydrogenase (LDH) assays. Osteogenic differentiation was assessed by alizarin red staining, and Alkaline Phosphatase (ALP) activity and intracellular Reactive Oxygen Species (ROS) levels were also analyzed.</p><p><strong>Results: </strong>The results showed that NaSe significantly enhanced cell viability in a dose-dependent manner at low doses (0.01-1μM), with the most effective dose being 1μM (p<0.05). LDH activity remained similar to the control within the 0.01-1μM range but increased significantly at higher concentrations (5-50 μM) in both 24- and 48-hour experiments (p<0.05). NaSe reduced intracellular ROS levels significantly between 0.01-1 μM, with 1 μM being the most effective concentration (p<0.05). The highest ALP activity was observed at 0.1 μM NaSe (p < 0.05), and calcium deposition increased in a concentration- dependent manner (p<0.05). The most effective dose for enhancing mineralization was 0.1 μM (p<0.05).</p><p><strong>Conclusion: </strong>This study demonstrates that NaSe has antioxidant and osteogenic effects at low doses in hFOB cells. These positive effects suggest that NaSe could be a promising candidate for in-vitro, in-vivo, and clinical trials, providing hope for new treatments for bone diseases.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946080","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":"Patents on Xylazine, a Drug Adulterant of Clinical Concern.","authors":"Alessia Catalano","doi":"10.2174/0109298673394075250723084954","DOIUrl":"https://doi.org/10.2174/0109298673394075250723084954","url":null,"abstract":"","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144946025","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":"MiRNA Regulations in Cardiotoxicity Induced by Oncologic Therapies and Possible Immune Response.","authors":"Desh Deepak Singh","doi":"10.2174/0109298673386907250730010201","DOIUrl":"https://doi.org/10.2174/0109298673386907250730010201","url":null,"abstract":"<p><p>Anti-cancer therapy offers significant risks for cardiovascular diseases, including hypertension, thromboembolic ischaemia, arrhythmias, dyslipidaemia, hyperglycemia, obesity, and high cholesterol. Cardiotoxicity is a leading cause of elevated mortality rates among cancer patients, and anti-cancer drugs often contribute to this issue. Emerging research highlights the role of microRNA (miRNAs) in regulating drug-induced cardiotoxicity by influencing genetic, epigenetic, transcriptional, and translational processes. MiRNAs have potential as biomarkers for early detection and treatment. Moreover, novel diagnostic and therapeutic approaches targeting miRNAs could improve the clinical management of cardiotoxicity in cancer patients. This study is based on regulatory mechanisms behind cardiotoxicity, including oxidative stress, vascular homeostasis, mitochondrial damage, apoptosis, and inflammation, and explores strategies for managing these complications in cancer therapy.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.5,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145014049","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}