Current medicinal chemistry最新文献

{"title":"Artepillin C as a Potential Anticancer Phytochemical: Chemistry, Bioavailability and Preclinical Insights.","authors":"Wesam Nofal, Abdulaziz A Aloliqi, Md Ali Mujtaba, Sorabh Lakhanpal, Shivani Sharma, Meenakshi Verma, Pratibha Pandey, Fahad Khan","doi":"10.2174/0109298673493386260711092835","DOIUrl":"https://doi.org/10.2174/0109298673493386260711092835","url":null,"abstract":"<p><p>Numerous plants are significant sources of bioactive chemicals with diverse therapeutic efficacy against numerous cancer types. Since ancient times, numerous plant types and their phytochemicals have been used for traditional and contemporary medicinal applications. Artepillin C (AC) is a biologically active phenolic component and prenylated derivative of p-coumaric acid of Brazilian green propolis (BGP), which is derived from Baccharis dracunculifolia (native to central and southeastern regions of Brazil). AC, the primary chemical marker of green propolis, is a key factor in its therapeutic efficacy. Several studies have substantiated its pharmacological activities, including neuroprotective, anti-inflammatory, antidiabetic, antitumor, gastroprotective, antioxidant, antimicrobial, and immunomodulatory effects. This review not only explains its anticancer potential but also explains its chemical properties, bioavailability, and production. Thus, we selected this compound for a thorough overview of its anticancer effects. A limited number of studies on this compound from the last 15 years have been synthesized from Science Direct, Medline, PubMed, Scopus, and Google Scholar search engines. Therefore, this review consolidates widespread research from 2010 to 2025 related to the pharmacological and anticancer efficacy of AC, which may potentiate its candidature as a potent anticancer drug for future research and therapeutic applications.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863953","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":"T Cell-associated Co-expression Module Genes as Prognostic Biomarkers and Predictors of Immunotherapy Response in Head and Neck Squamous Cell Carcinoma.","authors":"Qingmiao Shi, Zhenzhen Qi, Bingyang Shang, Xiaonan Geng, Zhibo Zhang, Di Huang, Xinjun Hu","doi":"10.2174/0109298673513005260806080704","DOIUrl":"https://doi.org/10.2174/0109298673513005260806080704","url":null,"abstract":"<p><strong>Introduction: </strong>The important roles of T cells in tumor progression support the development of a T cell-associated prognostic model for Head and Neck Squamous Cell Carcinoma (HNSCC).</p><p><strong>Methods: </strong>The single-cell RNA-seq (scRNS-seq) data from GSE181919 were processed via the Seurat package for quality control and cell annotation. hdWGCNA was used to identify T cell-associated co-expression modules. Key genes were screened by univariate and LASSO Cox regression in TCGA to build a RiskScore model, followed by validation in the GSE41613 and GSE117973 datasets. The correlations of the RiskScore with the immune microenvironment, predicted immunotherapy response, and drug sensitivity were analyzed, and preliminary in vitro assays were conducted to explore PIM2 function in HNSCC cells.</p><p><strong>Results: </strong>Ten cell populations were identified in HNSCC tissues, with T cells representing one of the major cell populations. An eight-gene RiskScore model (TNFRSF4, TNFRSF18, PIM2, CORO1B, CUL9, SOD1, ZC3H12D, and TUBA1B) was established, showing moderate but significant prognostic value. High-risk patients exhibited significantly poorer survival. A nomogram integrating the RiskScore and clinical features was further constructed. Additional analyses supported the prognostic value of the model in HPV-negative patients and showed that the RiskScore was independently associated with overall survival after adjustment for tumor purity. C-index comparisons further revealed higher and relatively consistent prognostic discrimination compared with two previously published HNSCC models. The high-risk group exhibited lower ImmuneScore, StromalScore, ESTIMATEScore, higher TIDE scores, and reduced immune infiltration. The RiskScore was significantly correlated with 11 candidate compounds, and preliminary in vitro assays showed that PIM2 knockdown suppressed malignant phenotypes of HNSCC cells.</p><p><strong>Discussion: </strong>The scRNS-seq and hdWGCNA analyses identified eight T cell-associated module genes related to HNSCC prognosis. High- and low-risk patients stratified by the RiskScore exhibited distinct immune infiltration and angiogenesis in their Tumor Microenvironment (TME). Drug sensitivity analysis predicted candidate compounds for HNSCC treatment, but further experimental and clinical validation is required.</p><p><strong>Conclusion: </strong>The T cell-associated prognostic model was associated with immune microenvironment features and predicted treatment response and may help predict HNSCC prognosis, providing candidate biomarkers for further investigation.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808369","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":"Blocking the RhoA/ROCK/cofilin/F-actin Pathway via Y27632 Protects Against MERTK-deficient Retinal Degeneration and Visual Function Impairment.","authors":"Lujia Feng, Ting Zhang, Yong Du, Yingyan Qin, Linbin Zhou, Bingyu Bai, Manjuan Peng, Lu Chen, Jin Ma, Shaochong Zhang","doi":"10.2174/0109298673436432260728094713","DOIUrl":"https://doi.org/10.2174/0109298673436432260728094713","url":null,"abstract":"<p><strong>Introduction: </strong>Retinitis pigmentosa (RP) is the most common inherited neurodegenerative retinal disease. Mer receptor tyrosine kinase (MERTK) mutations are associated with severe RP and dysfunction of the RPE. Previous studies have shown that MERTK and the Rho-associated coiled-coil-containing kinases (ROCK) pathway are involved in phagocytosis. However, the specific role of the ROCK pathway in the context of MERTK-associated RP needs to be revealed.</p><p><strong>Methods: </strong>We established an in vitro RP cellular model via MERTK depletion in human primary retinal pigment epithelium (HsRPE) cells by siRNAs, and RCS rats with spontaneous Mertk mutations were used as RP experimental animal models. Cell viability, apoptosis, phagocytosis, and visual function were measured by MTT, TUNEL and Annexin V/propidium iodide staining, phagocytosis assays and transmission electron microscopy, and electroretinography, respectively. The expression of RhoA, ROCK, Factin, and cofilin was determined by quantitative real-time PCR, western blotting, or immunofluorescence staining.</p><p><strong>Results: </strong>MERTK knockdown substantially impaired cell survival, promoted apoptosis, and suppressed phagocytosis in HsRPE cells. In RCS rats, Mertk mutations impaired phagocytosis, promoted apoptosis of the RPE, and damaged visual functions. Silencing MERTK upregulated the phosphorylation of RhoA, ROCK2, and cofilin and decreased F-actin expression in HsRPE cells. Blocking the RhoA/ROCK axis by a selective ROCK inhibitor, Y27632, rescued the MERTK depletion-induced phagocytic dysfunction and apoptosis of HsRPE cells and rat RPE.</p><p><strong>Discussion: </strong>Our results collectively indicate that MERTK maintains RPE survival and phagocytosis via regulating the RhoA/ROCK/cofilin/F-actin axis.</p><p><strong>Conclusion: </strong>This study demonstrates that MERTK deficiency impairs RPE phagocytosis and promotes cell apoptosis, leading to retinal degeneration and visual dysfunction. These findings provide new insight into RP pathogenesis and thereby offer valuable references for future drug development.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808001","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 and Evaluation of Naphthoxy and Phenoxy amide as Potential PARP 1 inhibitors: Molecular Docking and In Vitro Analysis.","authors":"Hardha Balachandran, Subhajit Majumder, Gowramma Byran, Kalirajan Rajagopal, Vishnu Kumar Malakar, Kaviarasan Lakshmanan","doi":"10.2174/0109298673424861260602102534","DOIUrl":"https://doi.org/10.2174/0109298673424861260602102534","url":null,"abstract":"<p><strong>Introduction: </strong>The objective was to design, synthesize, and evaluate novel naphthoxy and phenoxy amide derivatives as potential poly(ADP-ribose) polymerase-1 (PARP1) inhibitors, aiming to identify compounds with improved binding affinity, favorable pharmacokinetic properties, and enhanced anticancer activity compared with existing PARP1 inhibitors.</p><p><strong>Methods: </strong>A series of naphthoxy and phenoxy amide derivatives (A1-A9 and B1-B9) were evaluated using combined computational and experimental approaches. Molecular docking against PARP1 (PDB ID: 4ZZZ) was performed using Glide to assess binding affinity. ADMET and drug-likeness properties were predicted via SWISS-ADME, and binding free energies were refined using Prime MM-GB/SA. The lead compound B2 underwent a 50-ns molecular dynamics simulation using Desmond. In vitro cytotoxicity was assessed against MCF-7 human breast cancer cell lines.</p><p><strong>Results: </strong>Compounds B2 and B3 exhibited strong docking scores comparable to the reference PARP1 inhibitor and demonstrated favourable ADMET profiles. MM-GB/SA analysis supported their high binding affinity toward PARP1. Molecular dynamics simulations revealed that compound B2 formed a stable complex within the PARP1 active site. In vitro assays showed enhanced cytotoxic activity of B2 against MCF-7 cells.</p><p><strong>Discussion: </strong>The findings highlight the effectiveness of combining computational and biological approaches to identify promising PARP1 inhibitors, with B2 showing strong binding, stability, and cytotoxicity, despite lacking in vivo validation.</p><p><strong>Conclusion: </strong>Overall, compound B2 emerged as a promising PARP1 inhibitor with strong binding affinity, structural stability, and significant in vitro anticancer activity, warranting further optimization and preclinical investigation.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808248","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":"Integrative Genome-Wide Association Study with eQTL Combined with Transcriptome Analysis Reveals SLC18A1 as a Novel Biomarker for Small Cell Lung Cancer.","authors":"Yuanfeng Wei, YunYan Tai, Hong Zhu","doi":"10.2174/0109298673460777260725162800","DOIUrl":"https://doi.org/10.2174/0109298673460777260725162800","url":null,"abstract":"<p><strong>Introduction: </strong>Small cell lung cancer (SCLC) is a malignant tumor with low differentiation, high recurrence, and poor prognosis. The importance of SCLC prevention is becoming increasingly apparent. The aim of this study was to identify novel biomarkers that could predict SCLC risk by analyzing genome-wide association studies (GWAS) and expression quantitative trait loci (eQTL), along with transcriptomic data.</p><p><strong>Methods: </strong>The summary of GWAS data on SCLC was obtained from the IEU Open GWAS Project database. eQTL data from 31,684 participants were acquired from the eQTLGen Consortium. Mendelian randomization (MR) was applied to identify potential causal or protective genes (CGs) for SCLC by integrating GWAS and eQTL data. Then, sensitivity analyses and heterogeneity tests were conducted. Meanwhile, transcriptome data on SCLC were analyzed to obtain differentially expressed genes (DEGs). Next, novel biomarkers of SCLC were obtained by intersecting CGs and DEGs. Moreover, novel biomarkers were subjected to functional enrichment analysis. Immunohistochemistry (IHC) was used to verify the expression of hub genes.</p><p><strong>Results: </strong>Four novel biomarkers were identified based on GWAS, eQTL, and transcriptome data. We found that elevation of SLC18A1 could increase SCLC risk (OR=1.724; 95% CI: 1.070-2.778; P=0.025). In contrast, CD93 (OR=0.658; 95% CI: 0.444-0.975; P=0.037), TRPC6 (OR=0.346; 95% CI: 0.185-0.648; P<0.001) and SLA (OR=0.577; 95% CI: 0.362-0.921; P=0.021) might be associated with a reduced risk of SCLC. Moreover, SLC18A1 was expressed at higher levels, while CD93, TRPC6, and SLA were expressed at lower levels in SCLC compared to controls. IHC results showed that SLC18A1 was expressed at higher levels in SCLC patients (17/29, 58.6%) than in controls (7/29, 24.1%). KEGG analysis revealed that they were mainly enriched in the synaptic vesicle cycle and the cGMP-PKG signaling pathway.</p><p><strong>Discussion: </strong>These findings provide genetic evidence linking SLC18A1, CD93, TRPC6 and SLA to SCLC risk. The identification of SLC18A1 as a causal gene and of CD93, TRPC6 and SLA as protective genes offers new biomarkers for early detection of SCLC. The consistency between genetic association and expression differences further supports their potential as reliable biomarkers for SCLC. Our study highlights possible targets for future prevention or therapy; however, additional functional experiments and larger validation cohorts are required.</p><p><strong>Conclusion: </strong>The identified genes SLC18A1, CD93, TRPC6 and SLA are associated with SCLC risk, with SLC18A1 as a causal gene and the others as protective genes. They might serve as novel biomarkers for SCLC.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808282","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":"Lentinan Exerts Antitumor Activity in Non-small Cell Lung Cancer through P53-mediated Cytochrome c Release and Caspase Activation: A Preclinical Study.","authors":"Jiaqi Zhao, Wei Xie, Yuhang Zeng, Xin Jin, Guangzhe Li, Jia Liu, Changbao Chen, Xilin Wan","doi":"10.2174/0109298673470183260724005346","DOIUrl":"https://doi.org/10.2174/0109298673470183260724005346","url":null,"abstract":"<p><strong>Introduction: </strong>Lentinula edodes is regarded as a functional food and dietary supplement due to its significant nutritional and medicinal value. Lentinan (LTN) was reported to enhance immune function and exhibit antitumor activity. Although numerous studies have confirmed the inhibitory effect of LTN on tumors in vitro, its underlying mechanisms remain unclear.</p><p><strong>Methods: </strong>The present study was designed to investigate the anticancer effects of LTN and the associated mechanisms in a non-small cell lung cancer (NSCLC) cell model.</p><p><strong>Results: </strong>Lentinan has been demonstrated to exert anti-proliferative effects on NSCLC cells. Furthermore, studies indicate that it effectively induces cell cycle arrest, promotes apoptosis, and suppresses the migration and invasion capabilities of NSCLC cells. Mechanistically, LTN has been observed to upregulate the expression of P53-related proteins and downregulate matrix metalloproteinases (MMPs). These findings strongly suggest that LTN induces apoptosis in NSCLC cells through caspase activation mediated by mitochondrial cytochrome c release. We also employed Magnetic Resonance Imaging (MRI) to monitor tumor growth in mice, with results demonstrating a significant reduction in tumor size in the treatment group. Additionally, Laser Speckle Contrast Imaging was utilized to assess blood perfusion in the axillary region of these mice.</p><p><strong>Discussion: </strong>This study indicates that LTN, as a natural compound, exhibits the potential for multi-target action in the treatment of NSCLC. By inducing the mitochondrial apoptosis pathway and modulating tumor cell behavior, LTN demonstrates significant antitumor effects. These findings provide a solid experimental foundation for the further clinical development of LTN.</p><p><strong>Conclusion: </strong>These in vivo experiments further demonstrated that LTN exhibits a significant inhibitory effect on tumor growth in a lung cancer model.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808360","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":"Single-cell Transcriptome-wide Mendelian Randomization and Colocalization Converge on Astrocytic TRIM66 as a Candidate Driver and Potential Therapeutic Target for Trigeminal Neuralgia.","authors":"Hong Ye, Chaoya Jiang, Zhenyan Xu, Qiuhan Xu, Junjie Fang","doi":"10.2174/0109298673486365260720073144","DOIUrl":"https://doi.org/10.2174/0109298673486365260720073144","url":null,"abstract":"<p><strong>Background: </strong>Trigeminal Neuralgia (TN) is a disabling facial pain disorder with suboptimal pharmacological and surgical options. We hypothesized that genetic regulation of gene expression in specific brain cell types contributes to TN susceptibility and could nominate tractable therapeutic targets.</p><p><strong>Methods: </strong>Single-cell cis-eQTLs from 183 neuropathology-free donors were used to instrument cell-type-specific expression. Variants surpassing genome-wide significance (P < 5×10-8) were LD-pruned (1000 Genomes Phase 3 European; r2 < 0.001; 10-Mb window) and harmonized; instruments with F < 10 were excluded. The final set comprised 1,746 Single Nucleotide Polymorphisms (SNPs) mapping to 1,745 eGenes. Two-Sample Mendelian Randomization (TwoSampleMR, R) tested eight brain cell types against TN risk in FinnGen (Release 12; 2,226 cases; 435,371 controls). Wald ratios were used for single-SNP instruments and inverse-variance weighting for multiple instruments. False Discovery Rate (FDR) control was applied within cell type. Colocalization (coloc, R) assessed shared causal variants.</p><p><strong>Results: </strong>After pruning, 1,745 eGenes were analyzed across eight cell types. A single signal met within multiple-testing control: higher astrocytic Tripartite motif-containing 66 (TRIM66) expression associated with increased TN risk (Wald ratio; β = 0.3038, standard error (SE) = 0.0884, P = 5.87×10-4; odds ratio (OR) = 1.36, 95% confidence interval (CI) 1.14-1.61; FDR = 0.0869). Colocalization supported a shared causal variant between astrocytic TRIM66 expression and TN (PP.H4 = 0.81).</p><p><strong>Discussion: </strong>Astrocyte-specific regulation of TRIM66 may contribute to TN pathogenesis through neuroinflammatory pathways, offering a cell-type-resolved mechanistic perspective that complements existing models of TN biology.</p><p><strong>Conclusion: </strong>Genetic evidence suggests a potential role of astrocyte-mediated regulation of TRIM66 in TN susceptibility. Convergent MR and colocalization suggest TRIM66 as a potential cell-type-resolved candidate warranting further functional validation and therapeutic exploration.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808409","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":"Breast Cancer Therapy with Quantum Dots: NIR-II Image-Guided Interventions, Multimodal Treatment, and Translation.","authors":"Senyang Guo, Jianhua Liu, Biao Huang, Hongmei Zheng, Xinhong Wu","doi":"10.2174/0109298673458532260509140125","DOIUrl":"https://doi.org/10.2174/0109298673458532260509140125","url":null,"abstract":"<p><p>This systematic review evaluates quantum dots (QDs) as integrated theranostic platforms for breast cancer, combining second near-infrared (NIR-II) imaging with image-guided interventions and multimodal therapy. Literature was identified through a structured search of PubMed/MEDLINE, Web of Science, Scopus, CNKI, and Wan- Fang databases (January 2003-November 2025), followed by independent screening and quality appraisal by two authors using pre-defined inclusion/exclusion criteria. The review links QD composition and surface chemistry to optical performance, photothermal/ photodynamic/catalytic efficacy, and translational determinants (pharmacokinetics, biodistribution/clearance, immunocompatibility, and critical quality attributes (CQAs)). Compared with NIR-I dyes, NIR-II QDs improve intraoperative margin visualization and sentinel lymph node mapping and can guide photothermal and photodynamic treatment. Ligand-based and biomimetic strategies move beyond the enhanced permeability and retention effect, enabling trackable delivery and stimuli-responsive release of drugs and nucleic acids. We also summarize chemodynamic and sonodynamic approaches that complement phototherapies and may elicit immunogenic cell death. To enable comparability and translation, we recommend standardized reporting of optical/ultrasonic dosimetry, photothermal conversion efficiency, singlet-oxygen/ reactive oxygen species yields, temperature-time profiles, imaging depth/contrast, pharmacokinetic and clearance metrics, immune safety panels, and stability-linked CQAs. Task-driven design principles prioritizing low-toxicity cores, robust shells and coatings, and benchmarking against clinical standards are highlighted to support clinical translation.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808292","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":"Folate-ClipTAC: Design and Proof of Concept Study.","authors":"Xueyan Cao, Mengxiang Quan, Yun Zhang, Qingyang Chen, Xiangwei Xu, Zunyuan Wang","doi":"10.2174/0109298673445266260428072916","DOIUrl":"https://doi.org/10.2174/0109298673445266260428072916","url":null,"abstract":"<p><strong>Objective: </strong>Proteolysis-targeting chimaeras (PROTAC) technology is a rapidly emerging and intensively investigated strategy in the field of new drug research and development. However, due to the tripartite structure of PROTAC molecules, their molecular weights are generally high, which results in poor cell membrane permeability and targeting. A folate-CLIPTAC system was proposed to overcome these limitations.</p><p><strong>Methods: </strong>For proof of concept, the estrogen receptor (ER) was selected as the model target protein. Two clickable fragments (Part A and B) were synthesized first. Then, the stability, targeting, and membrane permeability were examined in vitro. Finally, the ER degradation effect was evaluated by Western blot (WB).</p><p><strong>Results: </strong>The structures of the two precursors were confirmed by NMR and MS. Both Part A and Part B were able to stably exist within 48 hours in artificial plasma, and they showed distinct targeting and membrane permeability properties when incubated with breast cancer cell line MCF-7 for a certain period. When administered at intervals, WB analysis revealed a pronounced reduction in target protein levels.</p><p><strong>Discussion: </strong>The folate-CLIPTAC system was designed to overcome poor permeability by using two small precursor molecular fragments that undergo in situ click reactions and achieve tissue targeting by introducing folate groups on both small molecular fragments. Subsequently, when the two precursor fragments encounter each other within the cell, a click reaction occurs, generating the PROTAC macromolecule in situ, thereby achieving degradation of the POI.</p><p><strong>Conclusion: </strong>Based on targeted degradation of ER as an example, this study provides primary proof-of-concept evidence for the folate-CLIPTAC system and lays the groundwork for future investigations.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808229","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":"Effectiveness of Pentoxifylline in Adult Patients with COVID-19: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.","authors":"Fatemeh Saghafi, Behrooz Heydari, Shima Motevali Haghighi, Amin Salehi-Abargouei, Seyedeh Mahla Hoseini, Ali Akrami, Adeleh Sahebnasagh","doi":"10.2174/0109298673495369260729070918","DOIUrl":"https://doi.org/10.2174/0109298673495369260729070918","url":null,"abstract":"<p><strong>Background: </strong>COVID-19 is characterized by immune dysregulation, endothelial dysfunction, and thrombo-inflammation. Pentoxifylline (PTX) has been proposed as an adjunctive modality for COVID-19. Regarding the inconsistent results of earlier trials, this systematic review was conducted to evaluate the efficacy of PTX in COVID-19 patients.</p><p><strong>Methods: </strong>For the study literature up to 16 September 2025 was systematically searched for randomized controlled trials evaluating pentoxifylline in COVID-19. Continuous outcomes were expressed as Mean Differences (MDs) or Standardized Mean Differences (SMDs), whereas dichotomous outcomes were expressed as Odds Ratios (ORs) with 95% confidence intervals. Risk of bias was assessed using the Cochrane RoB 2.0 tool.</p><p><strong>Results: </strong>Seven randomized trials (551 participants) were included. Pentoxifylline significantly improved oxygen saturation (SMD = 0.215; 95% CI: 0.016 to 0.415; P = 0.034) and was associated with reduced ICU admission (OR = 0.454; 95% CI: 0.224 to 0.917; P = 0.028). It also significantly reduced inflammatory markers, including CRP and ESR. Effects on mortality, mechanical ventilation requirement, and hospital length of stay were not statistically significant. Risk-of-bias assessments indicated generally low methodological concerns, with minor issues related to blinding. Publication bias could not be reliably assessed for several outcomes because of the small number of included studies.</p><p><strong>Conclusion: </strong>The results of the present study suggest that pentoxifylline may reduce systemic inflammation and improve oxygenation in hospitalized adults with COVID-19. It may also be associated with reduced ICU admission; however, its effects on mortality, mechanical ventilation requirement, and hospital length of stay remain uncertain. Larger, rigorously designed randomized trials are needed to confirm these findings.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148808279","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}