Current topics in medicinal chemistry最新文献

{"title":"Lipopolysaccharide-induced M1-type Macrophages Enhance T Cell Activity and Promote the Apoptosis of Hepatocellular Carcinoma Cells.","authors":"Mengchen Song, Tian Yang, Manzhen He, Guohong Cao","doi":"10.2174/0115680266394539250707102011","DOIUrl":"https://doi.org/10.2174/0115680266394539250707102011","url":null,"abstract":"<p><strong>Introduction: </strong>Hepatocellular carcinoma (HCC) is the most common type of liver cancer. M1 macrophages exhibit dual roles in the tumor microenvironment (TME), but the specific mechanisms underlying their involvement in HCC remain unclear.</p><p><strong>Methods: </strong>M1-polarized macrophages were differentiated from THP-1 monocytes employing Phorbol 12-Myristate 13-Acetate (PMA) and LPS. Then, macrophage activity was determined based on Mean Fluorescence Intensity (MFI), and their metabolic capacity was assessed according to extracellular acidification rate (ECAR) and Oxygen Consumption Rate (OCR). Quantitative Real-Time PCR (qRT-PCR) was performed to assess the expression of polarization-related genes.</p><p><strong>Results: </strong>The results showed that LPS at a concentration higher than 10 ng/mL significantly affected the viability of macrophages differentiated from THP-1 monocytes but promoted the MFI of CD86. At the same time, LPS treatment notably enhanced the M1 polarization of macrophages, as evidenced by the upregulated expression of markers related to the M1 phenotype. Moreover, the mitochondrial oxidative metabolism of M1 macrophages shifted toward aerobic glycolysis under LPS treatment. When T-cells and HCC cells were co-cultured with M1 macrophages, the reactivity of T cells was enhanced, and the level of Bax (an apoptosis-enhancer) was increased. At the same time, the expression of Bcl-2 (an apoptosis-suppressor) was suppressed.</p><p><strong>Discussion: </strong>LPS-induced M1 macrophages exert antitumor effects through metabolic reprogramming and immune modulation, though further mechanistic studies are needed.</p><p><strong>Conclusions: </strong>M1 macrophages inhibit HCC progression by activating T cells and inducing tumor cell apoptosis, offering novel insights for HCC immunotherapy.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636500","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":"Exosome-Mediated Strategies for Melanoma Eradication: A Comprehensive Review.","authors":"Lalit Kumar, Ritesh Rana, Isha Singh, Sumit Kumar, Vikas Aggarwal, Komal Komal, Vuluchala Jyothiraditya","doi":"10.2174/0115680266373170250624095758","DOIUrl":"https://doi.org/10.2174/0115680266373170250624095758","url":null,"abstract":"<p><strong>Introduction: </strong>Exosomes, which are vesicles that are naturally derived and contain a biomolecular payload, are promising vehicles for melanoma therapy because of their biocompatibility, targeting capabilities, and stability. This review emphasizes their capacity to circumvent the constraints of conventional treatments.</p><p><strong>Methods: </strong>We carried out a comprehensive search of PubMed, ScienceDirect, and Google Scholar for peer-reviewed articles published between 2015 and 2024 utilizing terms such as \"exosomes,\" \"melanoma,\" and \"chemotherapy.\" Studies on exosome characterization or non-melanoma malignancies were excluded from the inclusion criteria, which centered on exosome-based therapeutics.</p><p><strong>Results: </strong>Drugs delivered via exosomes, such as small interfering RNA (siRNA) and chemotherapeutics, demonstrated enhanced tumor accumulation, achieving 2.5 times greater bioavailability and resulting in a tumor reduction of 60 to 90% when compared to their free counterparts. Surface modifications, such as cRGD peptides, have been shown to enhance targeting capabilities, whereas exosome-mediated photodynamic therapy has been effective in augmenting reactive oxygen species generation and promoting apoptosis.</p><p><strong>Discussion: </strong>Exosomes tackle significant challenges such as drug resistance and systemic toxicity; however, they encounter obstacles related to scalability and immunogenicity. Their dual function in tumor advancement and treatment highlights the necessity for standardized protocols.</p><p><strong>Conclusion: </strong>Exosome-based therapies signify a groundbreaking advancement in the treatment of melanoma. Future endeavors should refine engineering methodologies, enhance production capabilities, and substantiate effectiveness through rigorous clinical trials.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607765","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":"Therapeutic Perspective of Prodrugs of Non-Steroidal Anti-Inflammatory Drugs and Antioxidants: An Approach to Reduce Toxicity and Enhance Efficacy.","authors":"Manoj Kumar Sahoo, Nidhi Agrawal, S K Lanjhiyana, Sanjay Kumar Bharti, Meenakshi Jaiswal","doi":"10.2174/0115680266360021250625073338","DOIUrl":"https://doi.org/10.2174/0115680266360021250625073338","url":null,"abstract":"<p><strong>Background: </strong>Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) are one of the most widely prescribed medications in the world, yet their applications as anti-inflammatory, analgesic, and anti-pyretic drugs remain principally restricted by their detrimental effects on the gastrointestinal tract (GIT) systems. The prodrug approaches have substantially combated the drawbacks of currently available marketed NSAIDs and also showed increased activity.</p><p><strong>Objective: </strong>In the present study, an extensive literature review on mutual prodrugs of NSAIDs with natural antioxidants has been presented.</p><p><strong>Methods: </strong>Different databases like ScienceDirect, Elsevier, PubMed, Google Scholar, etc. were used for an extensive search of articles related to NSAIDs, prodrug concepts, as well as research based on all of the NSAIDs-prodrug molecules prepared to date.</p><p><strong>Results: </strong>Recent developments in prodrug design have been explored that utilize naturally occurring antioxidants, including Thymol, Guaiacol, Menthol, Eugenol, Sesamol, Vanillin, and Umbelliferon, for the synthesis of mutual prodrugs by esterification methods. Many studies have shown that these prodrugs have significant stability in acidic pH while hydrolyzing in neutral and alkaline pH environments. This indicates their potential as advantageous therapeutic agents with enhanced safety profiles.</p><p><strong>Conclusion: </strong>The mutual prodrug strategy offers a chance in medicinal chemistry to enhance the therapeutic and clinical efficiency of a drug that has certain unfavorable qualities that limit its clinical utility. This review enlightens mutual prodrugs of NSAIDs and antioxidants that are less harmful and beneficial to mankind, respectively.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144607766","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":"Mining of Targeted Therapeutic Drugs for Hepatocellular Carcinoma based on Programmed Death-related Features and Construction of an Imaging Histology Diagnostic Model.","authors":"Juan Wang, Xiaoli Zhao, Chunguang Chen, Hongzhi Li, Chunli Liu, Zhongfeng Cui, Guangming Li","doi":"10.2174/0115680266397340250701110954","DOIUrl":"https://doi.org/10.2174/0115680266397340250701110954","url":null,"abstract":"<p><strong>Introduction: </strong>The programmed cell death (PCD) is crucial in inhibiting cancer cell proliferation and enhancing anti-tumor immune responses. Mining targeted therapeutics for liver hepatocellular carcinoma (LIHC) based on PCD genes and revealing their molecular mechanisms are essential for the development of effective clinical treatments for LIHC.</p><p><strong>Methods: </strong>Key genes associated with PCD characteristics of LIHC were identified in cancer genome mapping by the weighted gene co-expression network analysis (WGCNA). In this study, the performance and clinical value of key genes were evaluated by the Receiver operating characteristic curve (ROC). The relative expressions of genes related to PCD in hepatocellular carcinoma were measured employing QRT-PCR. The practical regulation of PCD-correlated key genes on the migration and invasion levels of LIHC cells was assessed by transwell and scratch healing assays. Functional and pathway characterization of gene sets was performed by Gene Set Enrichment Analysis (GSEA). CIBERSORT was used to assess immune cell infiltration in the samples. DSigDB and AutoDock tools were used for molecular docking of key genes and downstream targeted drugs. Impact omics characterization of the samples was determined by the alignment diagram.</p><p><strong>Results: </strong>Three genes, CAMK4, CD200R1, and KCNA3, were screened as key PCD-related genes in LIHC. Cellular experiments verified that CD200R1 promotes migration and invasion levels in hepatocellular carcinoma. GSEA showed that these three genes were enriched for cytokine release, apoptosis, and other pathways. In immune profiling, we revealed that the three genes were related to the infiltration of immune cells such as CD4+ memory T cells and CD8+ T cells. Molecular docking predicted potential drugs for the three biomarkers, among which CAMK4 was tightly bound to GSK1838705A and had the highest AUC in the ROC curve. In addition, we constructed an alignment diagram to accurately assess the imaging features of LIHC.</p><p><strong>Discussion: </strong>This study provided a new strategy for precision treatment of LIHC by screening key genes associated with PCD in LIHC (CAMK4, CD200R1, and KCNA3), revealing their roles in the regulation of the tumor immune microenvironment and predicting potential target drugs, as well as constructing a diagnostic model based on imaging histology; however, the study did not delve deeper into the long-range drug-target interaction mechanism and lacked molecular dynamics simulation validation, which limited the comprehensiveness of the results.</p><p><strong>Conclusion: </strong>This study identified key genes associated with PCD in LIHC, revealed its immunoregulatory mechanism, and predicted potential target drugs, providing new ideas for precision treatment and diagnosis of hepatocellular carcinoma.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599708","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":"An Updated Insight on Phyto-therapeutics and Their Novel Approaches in the Management of Brain Cancer.","authors":"Zulfa Nooreen, Vivek Kumar Gupta, Kanchan Singh, Ankita Wal, Awani Kumar Rai, Sudeep Tandon","doi":"10.2174/0115680266353935250622180309","DOIUrl":"https://doi.org/10.2174/0115680266353935250622180309","url":null,"abstract":"<p><p>Brain cancer patients may experience a wide range of excruciating and debilitating sensations as the tumours enlarge. This is frequently because the tumours press against the brain or obstruct normal brain and nerve impulses. While it is unusual for brain cancer to spread to other regions of the body, the majority of cases are quite aggressive. Particularly in older people, the majority of glioblastomas (around 80-90%) develop de novo, without any preceding clinical or histologic symptoms. Phytomolecules may possess anticancer effects by controlling many signalling pathways. They may enable cells to regenerate and offer a suitable environment for maintaining cells. Numerous plants were researched recently to find potent extracts and molecules. Berberine, muscone, schisandrin B, dioscin, naringenin and many others are used in the management of brain cancer. Recent developments in the treatment of brain cancer include the use of paclitaxel, temozolomide, and irinotecan. New medications, including thalidomide, suramin, and marimastat, can be used to treat brain tumour invasion and neoplastic angiogenesis. The databases PubMed, Scifinder, Google Scholar, Science Direct, and Scopus were examined for empirical research up to the end of March 2023. Here in the present comprehensive review article, we compiled extracts, phytomolecules and novel approaches like nanoparticle, liposomes and micelle reported in the management of brain cancer. Phytochemicals themselves may be functionalized into a portion of the micron-sized particles to help them pass across the bloodbrain barrier and, once released into the brain microenvironment, use their therapeutic properties for therapy. Additionally, liposomes are useful to encapsulate chemotherapy medications and enable focused distribution via the blood-brain barrier.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583344","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":"Leveraging Tubulin Isotype Structural Differences to Design Less Hematotoxic β5 Selective Covalent Inhibitors for NSCLC.","authors":"Sonia Kumari, Vruksha Arvind Raut, M Elizabeth Sobhia","doi":"10.2174/0115680266367194250619053553","DOIUrl":"https://doi.org/10.2174/0115680266367194250619053553","url":null,"abstract":"<p><strong>Aim: </strong>This study aims to discover and design β-5 tubulin-specific covalent inhibitors for non-small cell lung cancer (NSCLC) that can minimize hematotoxicity, a major side effect of current microtubule-targeting agents (MTAs).</p><p><strong>Background: </strong>Current microtubule-targeting drugs cause toxicities such as hematotoxicity and multidrug resistance (MDR). The colchicine binding site in β-5 has Cys-239, whereas β-1 has Ser- 239, allowing selective inhibition based on the reactivity differences for covalent reactions.</p><p><strong>Methods: </strong>β-5 and β-1 tubulin models were developed, and covalent docking and virtual screening were conducted to identify selective inhibitors targeting the β-5 tubulin colchicine binding site. Twenty hits were selected, and a comparative study was carried out between β-5 and β-1 to evaluate the selectivity and binding potential of the inhibitors.</p><p><strong>Results: </strong>Among the 20 identified hits, four compounds demonstrated selective inhibition of β-5 tubulin, exhibiting stronger binding affinity for β-5 over β-1 tubulin. Molecular dynamics studies further confirmed their stability and enhanced binding, highlighting their potential as promising candidates for further drug development.</p><p><strong>Conclusion: </strong>The study identified four novel β-5 tubulin-specific covalent inhibitors that may act as potential therapeutic agents for NSCLC, with the possibility of reduced hematotoxicity. These findings suggest that selective inhibition could help minimize side effects, addressing a critical need in cancer treatment.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559451","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":"MEF2C: A Novel Transcription Factor Implicated in Human Malignant Tumors.","authors":"Yining Pan, Jiayi Li, Haoran Liu, Jiayi Ma, Dongshuo Wang, Xiaolan Li, Chengfu Yuan","doi":"10.2174/0115680266359306250619210412","DOIUrl":"https://doi.org/10.2174/0115680266359306250619210412","url":null,"abstract":"<p><strong>Background: </strong>Myocyte enhancer factor 2C (MEF2C) is a pivotal transcription factor that is responsible for maintaining myocyte differentiation. MEF2C is multifunctional, participating in diverse biological processes, including cardiac morphogenesis, angiogenesis, neurogenesis, and cortical development. Emerging evidence has identified MEF2C as a novel oncogene with dual regulatory functions in tumorigenesis. However, the mechanisms by which MEF2C regulates the progression of various malignant tumors are unknown. Therefore, it is crucial to further investigate the multiple signaling pathways under different expression levels of MEF2C. In this review, the expression level of MEF2C in various malignant tumors and its specific pathways are described.</p><p><strong>Methods: </strong>This review systematically summarizes and critically analyzes the current studies on MEF2C's biological function in malignant tumors by comprehensively searching them through PubMed databases.</p><p><strong>Results: </strong>MEF2C demonstrates aberrant expression patterns across multiple tumor types, spanning both solid tumors (e.g., glioma, breast cancer, hepatocellular carcinoma) and hematological malignancies (e.g., leukemia). MEF2C orchestrates multiple oncogenic processes, including tumor cell proliferation, migration, and invasion, while also modulating cancer drug resistance and systemic manifestations, like cachexia and apoptosis resistance.</p><p><strong>Conclusion: </strong>Given its multifaceted roles in tumor initiation, progression, and clinic, MEF2C has the potential to serve as both a diagnostic biomarker and a therapeutic target for various malignancies.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144559452","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 New Biomarkers in the Early Diagnosis of Gestational Diabetes: A Mini Review.","authors":"Zehra İncedal Sonkaya","doi":"10.2174/0115680266361462250618084953","DOIUrl":"https://doi.org/10.2174/0115680266361462250618084953","url":null,"abstract":"<p><p>Gestational diabetes (GDM) has become a major public health problem in recent years and is one of the most debated topics in women's health. GDM is associated with serious health consequences for both the mother and the child in the short and long term. The prevalence of GDM varies between 0.6% and 20% (depending on the detection method, gestational age, and the population studied). Genetic, nutritional, epigenetic, immunological, and hormonal components have been identified in its pathophysiology. Today, the importance of identifying a biomarker to detect GDM from the beginning of pregnancy in women at high risk of developing GDM is frequently emphasized. In recent years, adipokines and cytokines have been reported to play important roles in the metabolic changes underlying GDM. The purpose of this study was to reveal the potential and importance of the recently identified chemerin, omentin-1, resistin, visfatin, and asprosin peptides with different mechanisms of action in the pathogenesis of GDM.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552581","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 Nanoformulations to Overcome Obstacles in Herbal Drug Delivery for Alzheimer's Disease.","authors":"Deepak Kumar, Pranay Wal, Ankita Wal, Mohd Qasid Lari, Astik Manju Ashesh, Dileep Kumar, Sandeep Kumar Singh, Bhupendra Kumar Singh, Ajay Kumar","doi":"10.2174/0115680266362594250527112018","DOIUrl":"https://doi.org/10.2174/0115680266362594250527112018","url":null,"abstract":"<p><strong>Introduction: </strong>Nanomedicine is a rapidly growing field in pharmaceutical science, driven by the enhanced quality of nano-formulations that improve the treatment of various diseases. Nano-sized novel drug delivery techniques for herbal pharmaceuticals have the potential to enhance activity and address concerns related to medicinal plants in the future. Natural chemicals show promise in various neurodegenerative diseases, but their permeability across the blood-brain barrier prevents them from reaching the nervous system. By improving molecular monitoring, synthesis, and diagnostics, pharmaceutical nanotechnology provides improved controlled drug delivery for the treatment of neurodegeneration.</p><p><strong>Method: </strong>The evaluated and investigated data from recent studies were gathered using Google Scholar as a search engine. We reviewed and analysed research publications from databases like Bentham Science, Elsevier, PubMed, and ScienceDirect, among others, to summarize the findings.</p><p><strong>Results: </strong>Curcumin, Centella asiatica, thymoquinone, Hypericum perforatum, Panax ginseng, quercetin, piperine, and a variety of other herbs and herbal medicines have all been examined for their potential to aid in the treatment of brain disorders like Alzheimer's disease. To enhance drug bioavailability in the brain, nanoformulations, including phytosomes, transferosomes, ethosomes, and niosomes, have been utilized as pharmaceuticals.</p><p><strong>Conclusion: </strong>Herbs and herbal medicines have been synthesized into nanoparticle form to enhance tissue distribution, achieve sustained delivery, and protect against physicochemical degradation while also increasing the solubility and bioavailability of poorly soluble herbal products. To overcome physiological complications, researchers must develop lab-scale approaches, characterization methodologies, and targeting tactics for nanoformulations with high translational potential early in product development.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526794","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":"Carbonic Anhydrase IX and Cyclooxygenase-2 Regulation in Renal Cell Carcinoma and Impact on Therapeutic Efficiency of Anti-CAIX CAR T cells.","authors":"Najla Santos Pacheco de Campos, Renata Schmieder Pivetta, Laura Libânio de Souza, Gabriela Sarti Kinker, Tiago da Silva Medina, Tiago Rodrigues, Eloah Rabello Suarez","doi":"10.2174/0115680266364293250613090952","DOIUrl":"https://doi.org/10.2174/0115680266364293250613090952","url":null,"abstract":"<p><strong>Background: </strong>Clear cell renal cell carcinoma (ccRCC) is the most prevalent of renal cancers, with a 5-year survival rate of less than 10% for metastatic cases. The most efficient current strategies to treat ccRCC in advanced settings slightly increase progression-free survival. Chimeric antigen receptor T cells (CAR T cells) targeting carbonic anhydrase IX (CAIX) have reemerged as a promising alternative to ccRCC treatment based on recent preclinical data. CAIX and cyclooxygenase- 2 (COX-2) are key players in tumor progression across various malignancies, overexpressed in 95% and 50% of ccRCC cases, respectively.</p><p><strong>Methods: </strong>This study employed in silico analysis to examine the expression of CAIX and COX-2 in ccRCC cell lines. The effects of celecoxib, anti-CAIX monoclonal antibodies, and anti-CAIX CAR T cells were evaluated using immunofluorescence microscopy and flow cytometry techniques.</p><p><strong>Results: </strong>Herein, we show a positive correlation between CAIX and COX-2 expression in ccRCC cell lines in vitro and in silico. Notably, COX-2 blockade with celecoxib led to a significant downregulation of CAIX expression in ccRCC cell lines. This effect is retroactive since treatment of these ccRCC cells with two different anti-CAIX monoclonal antibodies (mAbs) resulted in the downregulation of COX-2 expression. The association of celecoxib with anti-CAIX CAR T cell therapy impaired their cytotoxic potential over ccRCC in vitro, depending on CAIX cellular density.</p><p><strong>Conclusion: </strong>These findings suggest a regulatory interaction between CAIX and COX-2 levels, indicating that COX-2 inhibitors may diminish the efficacy of CAIX-targeted therapies and should be avoided in combination treatments.</p>","PeriodicalId":11076,"journal":{"name":"Current topics in medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144526793","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}