Drug Development Research最新文献_第9页

Potent Therapeutic Efficacy of 9-Bromo-Noscapine Against Breast Cancer Cells Via Enhanced Bioavailability of the Noscapine-Cyclodextrin Inclusion Complex 通过提高诺斯卡平-环糊精包合物的生物利用度，9-溴-诺斯卡平对乳腺癌细胞的有效治疗效果

IF 4.2 4区医学

Drug Development Research Pub Date : 2025-12-15 DOI: 10.1002/ddr.70208

Namita Bhoi, Lilesh Kumar Pradhan, Dibya Ranjan Sahoo, Manas Kumar Pradhan, Prajna Parimita Mohanta, Pratyush Pragyandipta, Iswar Baitharu, Pradeep Kumar Naik

{"title":"Potent Therapeutic Efficacy of 9-Bromo-Noscapine Against Breast Cancer Cells Via Enhanced Bioavailability of the Noscapine-Cyclodextrin Inclusion Complex","authors":"Namita Bhoi, Lilesh Kumar Pradhan, Dibya Ranjan Sahoo, Manas Kumar Pradhan, Prajna Parimita Mohanta, Pratyush Pragyandipta, Iswar Baitharu, Pradeep Kumar Naik","doi":"10.1002/ddr.70208","DOIUrl":"10.1002/ddr.70208","url":null,"abstract":"<div>\u0000 \u0000 <p>The poor bioavailability and low therapeutic indices of conventional cancer therapeutics hinder their efficacy despite their promising anticancer potential. This study presents an improved solubility and enhanced drug delivery system against breast cancer by complexing Bromo-Noscapine (9-Br-Nos) with Methyl-β-cyclodextrin (Mβ-CD). After synthesizing the inclusion complex, it was characterized using ultraviolet-visible (UV-Vis) spectroscopy, proton nuclear magnetic resonance (<sup>1</sup>H NMR), Fourier-transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), scanning electron microscopy (SEM), and thermogravimetric analysis (TGA). In addition, the arrangement of the drug molecule within the Mβ-CD cavity was confirmed by molecular docking and molecular dynamic simulation. The drug release profile, bioavailability, and anticancer activity of the complex were also evaluated <i>in vitro</i>. Moreover, the toxicity and metabolic clearance kinetics were assessed <i>in vivo</i> using animal model. Furthermore, to explore the molecular mechanism of the anticancer activity of the 9-Br-Nos-Mβ-CD inclusion complex FITC-annexin V apoptosis and western blot analysis were performed to explore the enhanced apoptotic cell death and the modulation of cancer-related proteins in breast cancer cells. In summary, this report demonstrated that the Noscapine-Cyclodextrin inclusion complex enhances the anticancer potential of 9-Br-Nos by modulating its bioavailability and persistence in breast cancer cells.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"87 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145761407","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}

引用次数: 0

Esketamine Protects the Blood–Brain Barrier Against Sepsis-Associated Brain Injury by Regulating the BDNF/TrkB Pathway 艾氯胺酮通过调节BDNF/TrkB通路保护血脑屏障免受败血症相关脑损伤

IF 4.2 4区医学

Drug Development Research Pub Date : 2025-12-15 DOI: 10.1002/ddr.70210

Weiqin Wei, Guofeng Wu, Yi Ge, Jialing Lu

{"title":"Esketamine Protects the Blood–Brain Barrier Against Sepsis-Associated Brain Injury by Regulating the BDNF/TrkB Pathway","authors":"Weiqin Wei, Guofeng Wu, Yi Ge, Jialing Lu","doi":"10.1002/ddr.70210","DOIUrl":"10.1002/ddr.70210","url":null,"abstract":"<div>\u0000 \u0000 <p>This study was designed to explore the effects of esketamine on cognitive deficits and blood–brain barrier (BBB) dysfunction in sepsis-associated encephalopathy (SAE). An in vivo SAE model was generated through the administration of lipopolysaccharide (LPS), and LPS-induced cognitive impairment in rats was evaluated using the Morris water maze (MWM) test. BBB disruption in vivo was assessed by measuring brain water content together with Evans blue dye penetration, while LPS-induced endothelial hyperpermeability in vitro was examined through FITC–dextran leakage. The protein expression of claudin-3 and ZO-1 was determined by western blotting. In addition, the levels of pro-inflammatory cytokines, cell apoptosis, autophagy, and the activity of the BDNF/TrkB pathway were examined. Rapamycin (Rap, an autophagy inducer) and K252a (a BDNF inhibitor) were used to determine whether the protective effects of esketamine were associated with autophagy and BDNF/TrkB signaling. Esketamine treatment significantly improved the LPS-induced cognitive dysfunction and neurological injury observed in vivo, and it also inhibited the production of pro-inflammatory cytokines and reduced cell apoptosis both in vivo and in LPS-treated hCMEC/D3 cells. Importantly, esketamine alleviated BBB hyperpermeability in vivo and prevented LPS-induced endothelial leakage in vitro. Moreover, esketamine suppressed LPS-induced autophagy, and the influence of esketamine on claudin-3 and ZO-1 expression was reversed when Rap was applied. Esketamine activated the BDNF/TrkB pathway, and the protective effects of esketamine on BBB integrity and autophagy in response to LPS were abolished by K252a. Taken together, these findings indicate that esketamine protects the BBB against SAE by activating the BDNF/TrkB pathway and inhibiting autophagy, providing a potential therapeutic strategy for SAE.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"87 1","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145761409","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}

引用次数: 0

Recent Progress of Molecular Design and Activities of Spleen Tyrosine Kinase (SYK) Inhibitors 脾酪氨酸激酶（SYK）抑制剂的分子设计与活性研究进展

IF 4.2 4区医学

Drug Development Research Pub Date : 2025-12-15 DOI: 10.1002/ddr.70206

Jiayi Shen, Jieman Lin, Anzhi Li, Yunyi Kong, Sheng Chen, Gonghui Li, Yongdong Li

引用次数: 0

NanoMIPs: Molecularly Imprinted Cavities for Smart and Controlled Anti-Cancer Drug Release 纳米ips：用于智能和可控抗癌药物释放的分子印迹空腔。

IF 4.2 4区医学

Drug Development Research Pub Date : 2025-12-10 DOI: 10.1002/ddr.70205

Rabab Fatima

{"title":"NanoMIPs: Molecularly Imprinted Cavities for Smart and Controlled Anti-Cancer Drug Release","authors":"Rabab Fatima","doi":"10.1002/ddr.70205","DOIUrl":"10.1002/ddr.70205","url":null,"abstract":"<div>\u0000 \u0000 <p>The inception of molecularly imprinted polymer technology at the nanoscale has marked a major advancement in targeted cancer therapy and diagnostics, representing the first systematic distribution of synthetic substitute to monoclonal antibodies in cancer therapeutics. Nano molecularly imprinted polymers (nanoMIPs) present a significant shift in cancer intervention with an antibody free strategy owing to its high specificity and adaptive recognition potential. Unlike conventional drug delivery platforms, nanoMIPs function as smart nanoscale scaffolds, capable of selectively encapsulating, accumulating and strategically releasing the chemotherapeutic agent in highly aggressive carcinomas and sarcomas. A key advantage of nanoMIPs based drug delivery system is their ability to create molecularly imprinted cavities that retain an exquisite structural memory of the target molecules after their removal establishing the first clinically viable, non biological alternative to therapeutic antibodies. This review provides an in-depth overview of the development, current state, and prospect of nanoMIPs, emphasizing their distinct molecular recognition properties and advantages over conventional antibody-based approach in cancer therapy. Several relevant chemotherapeutic drugs have been discussed for controlled and sustained delivery using nanoMIPs, for an improved biocompatibility, stability, solubility, biodegradability, and targeting efficiency across various cancer types. By integrating recent advancements in nanoMIPs based anticancer drug delivery system, this review seeks to provide a comprehensive framework for their continued development, optimization, and eventual clinical translation as the next generation antibody substitute in precision cancer therapeutics.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 8","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145721614","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}

引用次数: 0

Next-Generation Proteolysis-Targeting Chimeras in Precision Oncology: Multifunctional Designs, Emerging Modalities, and Translational Prospects in Targeted Protein Degradation 新一代蛋白水解靶向嵌合体在精准肿瘤学中的应用：靶向蛋白降解的多功能设计、新模式和转化前景。

IF 4.2 4区医学

Drug Development Research Pub Date : 2025-12-08 DOI: 10.1002/ddr.70192

Mohamed S. Nafie, Mohamed K. Diab, Asmaa S. A. Yassen, Amany M. Elshamy, Mohamed R. El Tohamy, Haytham O. Tawfik, Sherif Ashraf Fahmy

{"title":"Next-Generation Proteolysis-Targeting Chimeras in Precision Oncology: Multifunctional Designs, Emerging Modalities, and Translational Prospects in Targeted Protein Degradation","authors":"Mohamed S. Nafie, Mohamed K. Diab, Asmaa S. A. Yassen, Amany M. Elshamy, Mohamed R. El Tohamy, Haytham O. Tawfik, Sherif Ashraf Fahmy","doi":"10.1002/ddr.70192","DOIUrl":"10.1002/ddr.70192","url":null,"abstract":"<p>Proteolysis-targeting chimeras (PROTACs)-mediated protein degradation has been recently developed as a game-changing approach in oncology drug development. It represents a paradigm shift from traditional enzyme inhibition to selective protein degradation. PROTACs are different from regular small-molecule inhibitors because they are heterobifunctional compounds that use the ubiquitin-proteasome system to breakdown disease-causing oncogenic proteins. This review discusses the next generation of PROTAC platforms that innovate beyond traditional designs, such as dual-targeting PROTACS that present a novel mode of action, transcription factor-targeting PROTACs (TF-PROTACs), phosphorylation-dependent PROTACs (PhosphoTACs), and phosphorylation binding chimeras (PhosTACs). In kinase degradation, PROTACs have shown promise in addressing resistance mechanisms and carcinogenic drivers. Despite these advancements, issues with clinical pharmacokinetics, E3 ligase tissue selectivity, and subcellular localization persist. Additionally, the development of bio-responsive and spatially controlled PROTAC systems, such as photocaged and folate-caged PROTACs, was fully discussed, which achieves maximal precision in tumor selectivity. Furthermore, ARV-110 and ARV-471, as two representative PROTACs, have entered clinical trials, suggesting their potentially broader application. Accordingly, this review provides a critical overview of the design rationales, molecular mechanisms of action, therapeutic utilities, and synthetic issues associated with these innovative modalities, focusing on on their translational implication and pharmacokinetic limitations, as well as potential future clinical applications.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 8","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12686766/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145707562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Synthesis and Biological Evaluation of π-Conjugated Ir(III) Complexes: Cytotoxic Potential, DNA/HSA Binding, Thermodynamics, and Antioxidant Activity π共轭Ir（III）配合物的合成和生物学评价：细胞毒性、DNA/HSA结合、热力学和抗氧化活性。

IF 4.2 4区医学

Drug Development Research Pub Date : 2025-12-03 DOI: 10.1002/ddr.70204

Bhumika Joshi, Priyankar Paira, Kaliappan Uma, Murugesh Shivashankar

{"title":"Synthesis and Biological Evaluation of π-Conjugated Ir(III) Complexes: Cytotoxic Potential, DNA/HSA Binding, Thermodynamics, and Antioxidant Activity","authors":"Bhumika Joshi, Priyankar Paira, Kaliappan Uma, Murugesh Shivashankar","doi":"10.1002/ddr.70204","DOIUrl":"10.1002/ddr.70204","url":null,"abstract":"<div>\u0000 \u0000 <p>Metal-based complexes have greatly advanced anticancer therapy, but limitations of traditional drugs like cisplatin have driven the search for more stable and targeted metallodrugs. In this study, two novel Ir(III) complexes, PNIC and PNIT, incorporating a rigid Schiff base ligand (PNN) derived from 1,10-phenanthroline-5,6-dione and N,N-bis(4-formylphenyl)-N, N-diphenylbenzidine, were synthesized and characterized by NMR, FT-IR, HRMS, and UV–Vis spectroscopy. Both complexes exhibited large Stokes shifts (60 and 47 nm), high stability in GSH and PBS, and strong binding affinity toward DNA and HSA through hydrophobic and hydrogen bonding interactions. They also exhibited notable antioxidant activity and potent cytotoxicity against A549 lung cancer cells, with IC<sub>50</sub> values of 19.69 µM for PNIC and 16.86 µM for PNIT, and good selectivity toward normal HEK293 cells (SI = 10.5 and 13.6, respectively). These findings highlight the potential of both PNIC and PNIT as multifunctional Ir(III)-based anticancer candidates possessing excellent bio-stability and target selectivity.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 8","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-12-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145667650","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}

引用次数: 0

Study on the Mechanism of Aspirin Alleviating Kawasaki Disease With Coronary Artery Lesions by Inducing TRAF6 to Regulate STAT3 Ubiquitination and Inhibit Th17 Cell Differentiation 阿司匹林通过诱导TRAF6调节STAT3泛素化抑制Th17细胞分化减轻冠状动脉病变川崎病的机制研究

IF 4.2 4区医学

Drug Development Research Pub Date : 2025-11-30 DOI: 10.1002/ddr.70199

Xiangzhen Qu, Weina Ma, Xiujie Ma, Jian Liu, Xianghong Yang, Di He, Yi Sun

{"title":"Study on the Mechanism of Aspirin Alleviating Kawasaki Disease With Coronary Artery Lesions by Inducing TRAF6 to Regulate STAT3 Ubiquitination and Inhibit Th17 Cell Differentiation","authors":"Xiangzhen Qu, Weina Ma, Xiujie Ma, Jian Liu, Xianghong Yang, Di He, Yi Sun","doi":"10.1002/ddr.70199","DOIUrl":"10.1002/ddr.70199","url":null,"abstract":"<div>\u0000 \u0000 <p>Among multiple complications of Kawasaki disease (KD), coronary artery lesions (CALs) emerge as the clinically paramount concern. Aspirin therapy can reduce the incidence of KD with CAL, yet its mechanism remains unclear. This study principally investigated the mechanism by which aspirin is effective in treating KD with CAL. Peripheral blood samples from healthy, KD, and KD + CAL children were analyzed using RT-qPCR, western blot, and ELISA to assess the levels of TNF receptor associated factor 6 (TRAF6), signal transducer and activator of transcription 3 (STAT3), and Th17 cells. Spleen CD4<sup>+</sup> T cells extracted from mouse were initially activated and subsequently differentiated into Th17 cells for subsequent experiments. After aspirin treatment and the downregulation of TRAF6, IF, ELISA, western blot, and RT-qPCR assessed Th17 differentiation and TRAF6/STAT3 expression. Conversely, the effects of TRAF6 overexpression coupled with MG132 treatment on STAT3 expression were evaluated using RT-qPCR and western blot. Additionally, IP and IF assays were conducted to detect the interaction and ubiquitination modifications between TRAF6 and STAT3. The STRING online tool predicted the interacting proteins of TRAF6, which were then validated through cell experiments. In KD with CAL children, elevated Th17 cell count, reduced TRAF6 expression, and heightened STAT3 expression were observed in the peripheral blood. In cell experiments, aspirin boosted TRAF6 expression, downregulated STAT3, inhibited Th17 differentiation. Dampening TRAF6 expression in cells reversed the impact of aspirin. TRAF6 facilitated the ubiquitination of STAT3, triggering its protein degradation, while UBE2N interacted with TRAF6 to modulate STAT3 expression. This study found that aspirin upregulates TRAF6 to ubiquitinate STAT3, inhibiting Th17 differentiation and improving KD with CAL.</p>\u0000 </div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 8","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145647721","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}

引用次数: 0

Butyrate-Mediated Upregulation of Insulin Pathway Gene Expression Suggests Potential Antidiabetic Effects 丁酸盐介导的胰岛素通路基因表达上调提示潜在的抗糖尿病作用。

IF 4.2 4区医学

Drug Development Research Pub Date : 2025-11-30 DOI: 10.1002/ddr.70203

Elad Shapira, Irena Voinsky, Hana Klin, David Gurwitz

{"title":"Butyrate-Mediated Upregulation of Insulin Pathway Gene Expression Suggests Potential Antidiabetic Effects","authors":"Elad Shapira, Irena Voinsky, Hana Klin, David Gurwitz","doi":"10.1002/ddr.70203","DOIUrl":"10.1002/ddr.70203","url":null,"abstract":"<p>Type 2 diabetes (T2D) is a major cause of morbidity in developed countries and involves insulin resistance, a failure to correctly respond to insulin. Numerous studies in rodent T2D models suggested that the short-chain fatty acid butyrate, produced by gut microbiota species through fermentation of dietary fibers, improves T2D symptoms. Here, we explored the potential antidiabetic effects of butyrate by measuring the transcription of selected T2D-implicated genes in human B lymphocyte-derived lymphoblastoid cell lines (LCLs) from 17 unrelated adult healthy donors. Human LCLs were cultured with and without sodium butyrate (1 mM for 48 h), followed by RNA extraction and real-time PCR analysis of the selected T2D-related genes. Butyrate significantly upregulated the expression of <i>MT2A</i>, <i>RRAGD, IGF1R</i>, <i>OXTR</i>, and <i>INSR</i>, while no changes were observed in the expression of other selected genes implicated in insulin signaling. Our findings, which should be considered preliminary until demonstrated by in vivo T2D animal models, suggest that butyrate is a potential modulator of metabolic pathways relevant to insulin resistance. Future studies should explore the tentative therapeutic potential of butyrate and its upregulated genes using proteomics and metabolomics in relevant tissues of T2D animal models, possibly followed by controlled clinical trials.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 8","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12665645/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145647789","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

rFIP-GMI Suppresses IGF-1–Induced Invasion and Migration in Breast Cancer Cells via PI3K/Akt/β-Catenin Inhibition rFIP-GMI通过抑制PI3K/Akt/β-Catenin抑制igf -1诱导的乳腺癌细胞的侵袭和迁移

IF 4.2 4区医学

Drug Development Research Pub Date : 2025-11-26 DOI: 10.1002/ddr.70202

Wen-Ling Liao, Yu-Ying Wu, Yu-Fan Liu, Pei-Chi Lan, Yu-Chun Cheng, Yueh-Tzu Hung, Hsin-Wen Liang, Huei-Jane Lee, Yi-Hsien Hsieh, Chun-Wen Cheng

{"title":"rFIP-GMI Suppresses IGF-1–Induced Invasion and Migration in Breast Cancer Cells via PI3K/Akt/β-Catenin Inhibition","authors":"Wen-Ling Liao, Yu-Ying Wu, Yu-Fan Liu, Pei-Chi Lan, Yu-Chun Cheng, Yueh-Tzu Hung, Hsin-Wen Liang, Huei-Jane Lee, Yi-Hsien Hsieh, Chun-Wen Cheng","doi":"10.1002/ddr.70202","DOIUrl":"10.1002/ddr.70202","url":null,"abstract":"<p>Insulin-like growth factor-1 (IGF-I) promotes breast cancer (BC) progression by activating the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, which enhances invasion and migration through β-catenin–mediated epithelial–mesenchymal transition (EMT). Triple-negative breast cancer (TNBC), an aggressive BC subtype lacking hormone receptors and HER2 expression, exhibits high metastatic potential, poor prognosis, and limited therapeutic options. The recombinant fungal immunomodulatory protein from <i>Ganoderma microsporum</i> (rFIP-GMI) possesses anti-inflammatory, anti-allergic, and anticancer activities; however, its role in suppressing tumor invasion and migration remains unclear. In this study, we investigated the molecular mechanism of rFIP-GMI in TNBC cell lines, Hs578T and MDA-MB-231. Cell invasion and migration were evaluated using Boyden chamber and Transwell migration assays, while Western blot analysis and nuclear/cytoplasmic fractionation were employed to analyze protein expression and β-catenin localization. rFIP-GMI significantly inhibited IGF-1–induced invasion and migration in both TNBC cell lines. Mechanistically, rFIP-GMI suppressed PI3K and Akt phosphorylation, thereby activating glycogen synthase kinase-3 beta (GSK3β) and promoting β-catenin phosphorylation and degradation. This led to reduced nuclear β-catenin accumulation and downregulation of oncogenic targets, including c-Myc, cyclin D1, and MMP-9. Conversely, treatment with the proteasome inhibitor MG132 confirmed that rFIP-GMI stabilized cytoplasmic β-catenin phosphorylation and blocked its nuclear translocation. Collectively, these findings demonstrate that rFIP-GMI inhibits IGF-1–driven invasion and migration in TNBC by inactivating the PI3K/Akt/β-catenin axis, highlighting its potential as a therapeutic agent for this aggressive TNBC subtype.</p>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 8","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://analyticalsciencejournals.onlinelibrary.wiley.com/doi/epdf/10.1002/ddr.70202","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145603090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring the Analgesic and Antidiarrheal Properties of Angelicin Through Cyclooxygenase Inhibition and Μ-Opioid Receptor Interaction: In Vivo and In Silico Studies 通过环氧化酶抑制和Μ-Opioid受体相互作用探索当归素的镇痛和止泻作用：体内和计算机研究。

IF 4.2 4区医学

Drug Development Research Pub Date : 2025-11-26 DOI: 10.1002/ddr.70201

Sourav Bagchi, Dipu Bishwas, Mst Muslima Khatun, Most. Israt Jahan Oni, Md. Shimul Bhuia, Mohammed Alfaifi, Faisal H. Altemani, Abdullah H. Altemani, Salehin Sheikh, Muhammad Torequl Islam

{"title":"Exploring the Analgesic and Antidiarrheal Properties of Angelicin Through Cyclooxygenase Inhibition and Μ-Opioid Receptor Interaction: In Vivo and In Silico Studies","authors":"Sourav Bagchi, Dipu Bishwas, Mst Muslima Khatun, Most. Israt Jahan Oni, Md. Shimul Bhuia, Mohammed Alfaifi, Faisal H. Altemani, Abdullah H. Altemani, Salehin Sheikh, Muhammad Torequl Islam","doi":"10.1002/ddr.70201","DOIUrl":"10.1002/ddr.70201","url":null,"abstract":"<div>\u0000 \u0000 <p>Angelicin (AGN), an angular furocoumarin, exhibits notable anti-inflammatory and biological activities. However, its potential for managing pain and diarrhea, and the underlying mechanisms, remain poorly explored. This study aimed to investigate the analgesic and antidiarrheal properties of AGN and elucidate its possible mechanisms of action through in vivo and <i>in silico</i> approaches. Mice received AGN (2.5, 5, and 10 mg/kg, i.p), DFS (25 mg/kg, p.o), LOP (3 mg/kg p.o), and BSS (10 mg/kg, p.o), after 30 min of administration, for an analgesic test; 0.7% acetic acid at 10 mL/kg (i.p) induced writhing, observed latency, and number of writhing. Antidiarrheal activity was assessed by using castor oil (0.5 mL, p.o) induced diarrhea in mice, observing latency and number of diarrhea secretions over 3 h. Additionally, Molecular docking studies were performed to analyze AGN's interactions with cyclooxygenase (COX-1/2) enzymes and the µ-opioid receptor (MOR). Drug-likeness and toxicity profiles were predicted using SwissADME and ProTox-III. AGN demonstrated significant, dose-dependent analgesic and antidiarrheal effects. Its combination with standard drugs (DFS, LOP, BSS) showed enhanced efficacy. Molecular docking revealed strong binding affinities of AGN for COX-1 (−7.4 kcal/mol), COX-2 (−8.0 kcal/mol), and MOR (−7.1 kcal/mol). Pharmacokinetic predictions indicated good drug-likeness, and toxicity profiling suggested a favorable safety margin. These results strongly suggest that AGN is a promising dual-action therapeutic candidate for pain and diarrhea, likely mediated through COX inhibition and MOR interaction. Further studies are warranted to validate these mechanisms and develop optimized AGN-based formulations for clinical translation.</p></div>","PeriodicalId":11291,"journal":{"name":"Drug Development Research","volume":"86 8","pages":""},"PeriodicalIF":4.2,"publicationDate":"2025-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145603049","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}

引用次数: 0