Current medicinal chemistry最新文献

{"title":"Synthesis and Biological Evaluation of Glutathione-Responsive 2-Alkoxycarbonyl Allyl Niclosamide Prodrugs as Anticancer Agents.","authors":"Anuj K Singh, Zachary S Gardner, Greeshma P Kumpati, Mathew Jacob, Conor T Ronayne, Venkatram R Mereddy","doi":"10.2174/0109298673440168260809163531","DOIUrl":"https://doi.org/10.2174/0109298673440168260809163531","url":null,"abstract":"<p><strong>Introduction: </strong>Reprogrammed mitochondrial metabolism is recognized as an important target for anticancer therapy. Niclosamide, an FDA-approved anthelmintic agent with mitochondrial uncoupling activity, has shown promise as an anticancer agent. However, off-target mitochondrial toxicity can limit its utility at clinically effective doses.</p><p><strong>Methods: </strong>This study synthesized a variety of prodrugs based on the niclosamide template via the Baylis-Hillman (BH) reaction, with the hypothesis that niclosamide would be released upon reaction with cellular nucleophiles, including thiols.</p><p><strong>Results and discussion: </strong>Consistent with this hypothesis, BH-prodrugs release the parent niclosamide in the presence of cysteine and glutathione. The lead candidates exhibit cancer cell proliferation inhibitory properties comparable to those of the parent compound, niclosamide. Mitochondrial respiration assays demonstrated that niclosamide acutely uncouples mitochondria, whereas the lead BH-prodrug 6b does not, providing evidence for this prodrug strategy in mitigating off-target toxicities. In a dose-escalation study, lead compound 6b was well tolerated in healthy mice up to 30 mg/kg, with no mortality and no abnormal changes in grooming behavior or body weight. In a 67NR syngeneic breast cancer model, 6b produced 54% tumor growth inhibition by volume, compared with 19% for niclosamide.</p><p><strong>Conclusion: </strong>The studies herein provide a novel methodology for the application of BH prodrugs on the niclosamide template and anticancer applications.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891238","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":"Pharmacovigilance Insights into Route-Stratified Adverse Events of Platinum-Based Drugs.","authors":"Xiaoqun Lv, Xibing Zhuang, Qi Zhang, Shu Wang, YanYan Zhu, Qing Zhai","doi":"10.2174/0109298673484441260806093741","DOIUrl":"https://doi.org/10.2174/0109298673484441260806093741","url":null,"abstract":"<p><strong>Introduction: </strong>Platinum-based drugs, including cisplatin, carboplatin, and oxaliplatin, are widely used in the treatment of various malignancies. However, the route-stratified adverse-event reporting patterns have not been fully characterized. This study aims to describe and characterize the patterns and time-to-onset distributions of adverse events (AEs) for platinum drugs across intravenous (IV), intraperitoneal (IP), and intraarterial (IA) routes.</p><p><strong>Methods: </strong>Data covering the period from 2004Q1 to 2024Q4 were collected from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Disproportionality analyses were conducted to identify potential safety signals by platinum agent and route. The identified signals were then classified according to clinical priority, a categorization based on clinical relevance, reporting rate, fatality rate, and signal stability. Furthermore, time-to-onset profiles were analyzed using Kaplan-Meier analysis, the log-rank test, and Weibull shape parameter modeling.</p><p><strong>Results: </strong>The study identified AE reports associated with cisplatin (5,783 IV, 193 IP, 135 IA), carboplatin (17,091 IV, 115 IP, 171 IA), and oxaliplatin (18,845 IV, 170 IP, 108 IA). IP reports were more frequently submitted for female patients, whereas IA reports were more frequently submitted for male patients, likely reflecting route-associated clinical indications. AE reporting profiles differed by platinum agent and route, with partial overlap. Among the identified AEs, twelve AEs were classified as high clinical priority. Of these, hepatic failure was the most frequently reported high-priority AE for both IV cisplatin and IV oxaliplatin. Notably, all IV platinum agents exhibited early failure- type patterns. The cumulative reporting distributions following IV administration differed significantly by drug. Patients treated with cisplatin showed shorter time to onset, with a median of 16 days (IQR: 7-46 days).</p><p><strong>Discussion: </strong>Through a comprehensive analysis of FAERS data, this study has identified and characterized the AE signals for platinum drugs across IV, IP, and IA routes, assessed clinical priorities, and elucidated temporal characteristics. These findings should be interpreted as exploratory pharmacovigilance signals because FAERS does not support incidence estimation, comparative risk assessment, or causal inference. Therefore, large-scale prospective studies are warranted to validate and extend these results.</p><p><strong>Conclusion: </strong>This study identified differences in AE reporting profiles and time-to-onset patterns stratified by platinum agent and administration route. This underscores the importance of pharmacovigilance and the integration of safety monitoring systems to facilitate timely identification and management of AEs in clinical practice.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891210","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":"Identification of Shared Associated Genes and Potential Molecular Mechanisms Between Psoriasis and Ischemic Stroke Based on Bioinformatics, Machine Learning, and Molecular Dynamics Simulation.","authors":"Mengyao Bi, Xinmin Li, Jing Wang, Fangjie Yang, Pengxue Guo, Chunlin Ren, Zhenfei Duan, Yuting Kong, Hanxue Li, Mengmeng Ma, Yasu Zhang","doi":"10.2174/0109298673490100260812043453","DOIUrl":"https://doi.org/10.2174/0109298673490100260812043453","url":null,"abstract":"<p><strong>Introduction/objective: </strong>Psoriasis is associated with an increased risk of Ischemic Stroke (IS), but the underlying mechanisms remain unclear. This study aims to identify shared associated genes and explore potential mechanisms underlying psoriasis and IS.</p><p><strong>Methods: </strong>Gene expression datasets from the GEO database were analyzed to identify common Differentially Expressed Genes (co-DEGs). Integrative bioinformatics analyses, machine-learning algorithms, single-cell RNA sequencing, molecular docking, and molecular dynamics simulations were employed to identify candidate shared genes and investigate the potential molecular mechanisms.</p><p><strong>Results: </strong>We identified 57 co-DEGs shared between psoriasis and IS. Enrichment analyses indicated that these genes were mainly associated with immune and inflammatory pathways, including NET formation, NF-κB, TLR, and IL-17 signaling pathways. TLR2 and TNFSF10 were identified as shared associated genes and remained significant across leave-one-out sensitivity analyses, demonstrating the robustness of their differential expression. Single-cell analysis revealed that TLR2 and TNFSF10 were mainly expressed in macrophages, NK cells, and smooth muscle cells. Epigallocatechin gallate was identified as a candidate compound for further investigation.</p><p><strong>Discussion: </strong>Our integrative analysis highlights TLR2 and TNFSF10 as potential mechanistic candidates associated with persistent immune activation, endothelial dysfunction, and vascular injury. These genes may participate in interconnected inflammatory processes involving TLR, IL-17, NF-κB, and NET-related pathways, providing a potential molecular link between psoriasis and IS.</p><p><strong>Conclusion: </strong>Chronic inflammation and immune dysregulation may contribute to psoriasis and IS comorbidity. TLR2 and TNFSF10 were identified as shared associated genes. These findings provide exploratory insights into the immunoinflammatory mechanistic association between psoriasis and IS.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886567","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":"The Association of Serum Calcium Levels with the Risk of Metabolic Syndrome: A Meta-Analysis of Observational Studies.","authors":"Mi Tian, Jingjie Luan, Xue Li, Yingsheng Pei, Li Lu, Sijie Gu, Airefate Tusunkali, Zhiyi Li, Jia He","doi":"10.2174/0109298673474975260804093837","DOIUrl":"https://doi.org/10.2174/0109298673474975260804093837","url":null,"abstract":"<p><strong>Introduction: </strong>Although some studies have examined the relationship between serum calcium levels and Metabolic Syndrome (MetS), results remain inconsistent, and a quantitative synthesis is lacking. This meta-analysis aims to consolidate existing evidence and clarify the association between serum calcium levels and MetS risk.</p><p><strong>Methods: </strong>We systematically searched seven databases up to May 1, 2025, for observational studies comparing serum calcium in MetS versus non-MetS groups. A random-effects model was applied to pool Odds Ratios (ORs) and Weighted Mean Differences (WMDs) with 95% Confidence Intervals (CIs). Subgroup analyses, sensitivity analyses, and publication bias assessments were also performed.</p><p><strong>Results: </strong>Twenty-three studies (n=67,148) showed a positive association in categorical data analysis (OR=1.79, 95% CI: 1.37-2.34, P<0.0001, I2=82.3%), whereas continuous data did not reveal a significant difference (WMD=0.0107 mmol/L, 95% CI: -0.0078-0.0291, P=0.258, I2=89.4%). Subgroup analysis tentatively suggested a higher MetS risk in elderly (65 years old or older) populations (OR=2.44, 95% CI: 1.70-3.51), though this finding was based on a limited number of studies. Substantial heterogeneity was observed in both analyses.</p><p><strong>Discussion: </strong>These findings suggest a potential association between elevated serum calcium and increased MetS risk, which may follow a nonlinear, threshold-like pattern. The observed age-related difference, while notable, should be interpreted with caution given the small number of studies in the elderly subgroup. The inconsistency between categorical and continuous results underscores the need for standardized protocols and further prospective investigations to clarify the nature of this relationship.</p><p><strong>Conclusion: </strong>Elevated serum calcium may be associated with an increased risk of MetS, with a possibly more pronounced effect suggested in older adults. However, these preliminary observations require validation in well-designed prospective studies with agespecific analyses.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886577","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 Inhibitory Impacts of Anamorelin on Colorectal Cancer Proliferation via Regulation of Transketolase.","authors":"Zhenkai Fu, Saiying Wang, Fei Li, Wenna Liu, Yujia Zhao, Dan Wu, An Liu, Ying Liang","doi":"10.2174/0109298673450549260810115103","DOIUrl":"https://doi.org/10.2174/0109298673450549260810115103","url":null,"abstract":"<p><strong>Background/objectives: </strong>Colorectal cancer (CRC) is a major cause of cancer- related deaths worldwide and poses a significant global health challenge. Metabolic reprogramming, including transketolase (TKT) upregulation in the pentose phosphate pathway, is a hallmark of CRC. Drugs targeting TKT have shown promise in cancer treatments; however, their mechanisms are poorly understood.</p><p><strong>Methods: </strong>In this study, by integrating bioinformatics analysis of 494 cases from the TCGA database, we identified that transketolase (TKT) may be a potential key target for colorectal cancer. Furthermore, we systematically screened the Natural Product Library for HTS (L6000) TargetMol using molecular docking technology.</p><p><strong>Results: </strong>Anamorelin was identified, which exhibited optimal spatial matching with the ligand in the target protein crystal structure. As a selective growth hormone secretagogue receptor (GHS-R) agonist, anamorelin has been clinically demonstrated to significantly improve appetite and increase lean body mass in patients with CRC by activating the GHS-R signaling pathway and is currently used for treating cancer cachexia in patients with advanced CRC. However, existing research has primarily focused on its metabolic benefits, and its direct effects on tumor cell proliferation, migration, and related molecular mechanisms remain unclear. This study elucidated the regulatory relationship between anamorelin and TKT in CRC, thereby addressing a critical knowledge gap in this field (Fig. 1).</p><p><strong>Discussion: </strong>These findings reveal a previously unrecognized antitumor mechanism of anamorelin through TKT inhibition. These findings provide preliminary evidence of a TKT-associated mechanism of anamorelin in CRC, offering dual benefits in cachexia management and tumor suppression, and warrant further validation in advanced preclinical models. Further preclinical and clinical validation is warranted to translate these insights into practice.</p><p><strong>Conclusion: </strong>By integrating bioinformatics analysis with in vitro cellular experiments, we systematically validated the molecular mechanism whereby anamorelin inhibited tumor cell proliferation and migration via the targeted suppression of TKT. These findings provide a theoretical foundation for the development of novel metabolism-based therapeutic strategies for CRC, ultimately contributing to improved clinical outcomes.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886516","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":"CDC20B Dysregulation: Links to Tumor Prognosis and Immunity.","authors":"Hongrong Wu, Liangli Hong","doi":"10.2174/0109298673463433260729044815","DOIUrl":"https://doi.org/10.2174/0109298673463433260729044815","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to clarify the pan-cancer expression pattern, upstream regulatory mechanisms, prognostic relevance, and immune associations of CDC20B.</p><p><strong>Method: </strong>Using public databases (GTEx, GEO, and TCGA), we examined CDC20B expression and its associations with prognosis and tumor immunity across multiple cancers. Immunohistochemistry (IHC) on an independent clinical cohort was performed to validate CDC20B upregulation in tumor tissues. Promoter methylation, genetic alterations, and immune infiltration were analyzed using bioinformatics tools (cBioPortal, UALCAN, TIMER2.0, ESTIMATE). Functional enrichment was assessed by GSEA and single-cell state analysis (CancerSEA).</p><p><strong>Results: </strong>CDC20B was markedly upregulated in most tumor types (p < 0.001), with strong diagnostic efficiency (AUC > 0.7 in 15 cancers) and potential regulation by promoter hypomethylation. IHC confirmed its overexpression in clinical tumor tissues. However, the prognostic impact of CDC20B was cancer-type-specific: high expression correlated with poor overall survival in UCS, LGG, KIRC, and OV, but with favorable survival in BRCA, LUAD, and PAAD. CDC20B expression was associated with immune infiltration patterns, showing negative correlations with ImmuneScore in most cancers but positive correlations with CD8+ T cells in PAAD. Functional analyses indicated involvement in EMT, KRAS/NF-κB signaling, and DNA damage response pathways.</p><p><strong>Discussion: </strong>The dual prognostic role of CDC20B suggests context-dependent functions, likely influenced by tumor microenvironment composition and underlying oncogenic programs. Promoter hypomethylation emerges as a potential epigenetic driver of overexpression. The associations with immune modulation and genomic instability suggest that CDC20B is a candidate biomarker, though causal relationships require experimental validation.</p><p><strong>Conclusion: </strong>CDC20B may contribute to tumor progression in a context-dependent manner, with its prognostic impact varying across cancer types. Its role in tumor immunity and oncogenic pathways warrants further investigation, particularly in stratified patient populations.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886462","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":"Applications of Graphene in Biomedical Fields and Advances in Its Antitumor Research.","authors":"Huifang Zang, Yan Gao, Lu Liu, Yifei Wang, Jing Lyu, Bonian Zhao","doi":"10.2174/0109298673450850260804060949","DOIUrl":"https://doi.org/10.2174/0109298673450850260804060949","url":null,"abstract":"<p><p>Graphene is a two-dimensional crystal formed by carbon atoms through sp2 hybridization, exhibiting exceptional physicochemical properties such as ultra-high strength, high specific surface area, and outstanding chemical stability. It has garnered extensive attention across multiple fields and emerged as a core focus in interdisciplinary research. This paper systematically reviews the fundamental information and key physicochemical properties of graphene and its derivatives, elucidating their differences in structure, performance, and functionality. It analyzes the research progress of graphene-based materials over the past decade, focusing on the latest achievements in the biomedical field. Based on graphene heating films, this study delves into the mechanism of far-infrared radiation. This study systematically addresses core issues in biomedical applications. It focuses particularly on variations in biocompatibility and safety, as well as potential influencing factors. Existing biomedical applications of graphene and its derivatives are enumerated, elucidating the biological activity of graphene's far-infrared radiation. Its antitumor mechanisms are analyzed at both in vitro and in vivo levels, though relevant clinical research data remains scarce. This underscores the immense application potential and translational value of graphene-based materials in biomedicine. Finally, it analyzes existing barriers in the graphene industry from three aspects: standard establishment, safety assessment, and mechanism clarification. It identifies priority development directions for graphene materials: improving the quality standards system, optimizing safety and biocompatibility, supplementing clinical data, and deepening research on therapeutic mechanisms. These are key prerequisites for graphene-based materials to break through laboratory research limitations and advance toward clinical application, which is crucial for accelerating their industrialization in the biomedical field.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886413","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":"Apigenin Protects Against Ischemic Stroke Through Anti- Inflammatory Mechanisms: A Study Combining Comprehensive Network Analysis, Mendelian Randomization and Animal Experiments for Validation.","authors":"Jinwen Yao, Xu Wang, Dexi Zhao","doi":"10.2174/0109298673468784260728054736","DOIUrl":"https://doi.org/10.2174/0109298673468784260728054736","url":null,"abstract":"<p><strong>Background and objective: </strong>There is a well-established link between inflammation and Ischemic Stroke (IS) pathology. A natural compound, Apigenin (APG), has a neuroprotective effect. However, the specific mechanisms underlying the anti-inflammatory effects of APG and its protective effects on the blood-brain barrier following IS are unclear. This study aimed to explore the mechanisms behind the anti-inflammatory effect of APG in IS.</p><p><strong>Methods: </strong>Male Sprague-Dawley rats were used to establish a model of unilateral middle cerebral artery occlusion (MCAO) and were administered APG by oral gavage at doses of 30, 60, or 120 mg/kg for 7 days. On the following day, brain tissues were collected after MCAO. Brain injury was evaluated by measuring brain water content, hematoxylin and eosin (H&E) staining, and Evans blue extravasation. To investigate potential proteins associated with inflammation, methods such as molecular docking, molecular dynamics simulations, Mendelian randomization analysis, immunohistochemistry, and Western blotting were employed.</p><p><strong>Results: </strong>APG therapy has improved neurological deficiencies, lowered brain edema, and improved blood-brain barrier integrity. It has also resulted in decreased levels of inflammatory proteins TLR4, MyD88, NFκB, IL1β, MMP9, and iNOS after IS. Furthermore, IL1R2 was identified as a potential predictive target for IS.</p><p><strong>Discussion: </strong>APG can repair nerve damage post-IS, with its protective effects mediated by anti-inflammatory mechanisms. The TLR4/myD88/NF-kB signaling pathway is a protective pathway of the body. APG may exert a protective effect on the blood-brain barrier after IS through the TLR4/MyD88/NF-kB signaling pathway.</p><p><strong>Conclusion: </strong>APG can protect against IS by inhibiting the inflammatory response, providing a theoretical basis for clinical translation and further experimental research of APG.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863872","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":"Integrated Transcriptomic Analysis and Molecular Modeling Identify ENO1 and Naftopidil as Candidates for Chronic Myelomonocytic Leukemia.","authors":"Minming Li, Suxia Geng, Lingji Zeng, Jianyu Weng, Xin Huang, Chengxin Deng, Xin Du","doi":"10.2174/0109298673521243260810063309","DOIUrl":"https://doi.org/10.2174/0109298673521243260810063309","url":null,"abstract":"<p><strong>Introduction: </strong>In-depth analysis of the biological status of Hematopoietic Stem Cells (HSCs) may reveal the intrinsic pathological mechanism of Chronic Myelomonocytic Leukemia (CMML).</p><p><strong>Materials and methods: </strong>Single-cell dataset GSE211033 and bulk transcriptomic dataset GSE102312 were analyzed. Single-cell preprocessing was performed using the Seurat package, cell-cell communication was analyzed with CellChat, and HSC-associated co-- expression modules were identified via hdWGCNA. Pathway and candidate-compound analyses were conducted using Enrichr with the DSigDB database. Molecular docking and a 100 ns molecular dynamics simulation were performed with GROMACS 2025, and the function of ENO1 was preliminarily assessed in myeloid leukemia cell lines.</p><p><strong>Results: </strong>Ten major cell populations were identified, among which HSCs comprised 14,729 cells. Seven HSC co-expression modules were classified. Among 25 genes represented in the M1 hub-gene network, ENO1 was the only evaluated candidate that showed a distinct difference between CMML samples and healthy controls. ENO1 knockdown reduced the viability of HL-60 and MV-4-11 cells in a time-dependent manner. High ENO1 expression was associated with enrichment of cell-cycle, DNA damage- response, and energy-metabolism pathways. Naftopidil ranked first among the significant HL-60-associated candidates screened from the DSigDB. Molecular docking and 100 ns molecular dynamics simulation revealed that the ligand dynamically interacted with ENO1 following conformational rearrangement, although direct binding remains to be experimentally validated.</p><p><strong>Discussion: </strong>ENO1 emerged as an HSC-associated candidate gene with a potential role in supporting the metabolic and proliferative state of CMML-related hematopoietic cells. Naftopidil was computationally predicted as a candidate ENO1-binding compound, but its direct binding and therapeutic activity require experimental validation.</p><p><strong>Conclusion: </strong>These findings provide a hypothesis-generating basis for further investigation of ENO1 and naftopidil in CMML-specific models, primary samples, and in vivo studies.</p>","PeriodicalId":10984,"journal":{"name":"Current medicinal chemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2026-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148863866","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":"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}