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c-KIT Small Molecule Inhibitors as a Therapeutic Strategy for Melanoma: Clinical Insights, SAR, and Future Directions c-KIT小分子抑制剂作为黑色素瘤的治疗策略:临床见解,SAR和未来方向。
IF 3.6 3区 医学
Archiv der Pharmazie Pub Date : 2025-10-03 DOI: 10.1002/ardp.70113
Shubham C. Rivonker, Hossam Nada, Cho Jaemin, Yong-Jun Kwon, Kyeong Lee
{"title":"c-KIT Small Molecule Inhibitors as a Therapeutic Strategy for Melanoma: Clinical Insights, SAR, and Future Directions","authors":"Shubham C. Rivonker,&nbsp;Hossam Nada,&nbsp;Cho Jaemin,&nbsp;Yong-Jun Kwon,&nbsp;Kyeong Lee","doi":"10.1002/ardp.70113","DOIUrl":"10.1002/ardp.70113","url":null,"abstract":"<div>\u0000 \u0000 <p>The proto-oncogene c-KIT plays a key role in several cellular processes such as cell growth, survival, and proliferation. The overexpression of c-KIT has been implicated with the pathogenesis of several malignancies, such as gastrointestinal stromal tumors, acute myeloid leukemia (AML), mastocytosis, and melanoma. Mutation of c-KIT has been observed in acral, mucosal, and chronically sun-damaged melanoma subtypes marking it as a key therapeutic target for melanoma. Moreover, the increasing incidence and mortality rate associated with melanoma further marks the importance of developing new therapeutic modalities. Herein, the progress in the design, structure–activity relationship, mechanisms, and development of c-KIT small molecule inhibitors for melanoma is discussed with the aim of guiding future c-KIT-based melanoma therapeutics.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 10","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211108","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Exploring the Antidiabetic Potential of Heterophylliin A From Elaeocarpus grandis 巨腕树异茶碱A抗糖尿病作用的研究。
IF 3.6 3区 医学
Archiv der Pharmazie Pub Date : 2025-10-03 DOI: 10.1002/ardp.70110
Sherif A. Maher, Radwa Taher Mohie el-dien, Muhamad Mustafa, Amgad I. M. Khedr, Ahmed M. Sayed, Usama Ramadan Abdelmohsen, Mostafa A. Fouad, Mohamed Salah Kamel
{"title":"Exploring the Antidiabetic Potential of Heterophylliin A From Elaeocarpus grandis","authors":"Sherif A. Maher,&nbsp;Radwa Taher Mohie el-dien,&nbsp;Muhamad Mustafa,&nbsp;Amgad I. M. Khedr,&nbsp;Ahmed M. Sayed,&nbsp;Usama Ramadan Abdelmohsen,&nbsp;Mostafa A. Fouad,&nbsp;Mohamed Salah Kamel","doi":"10.1002/ardp.70110","DOIUrl":"10.1002/ardp.70110","url":null,"abstract":"<div>\u0000 \u0000 <p>The antidiabetic efficacy of <i>Elaeocarpus grandis</i>, belonging to the Family Elaeocarpaceae, was investigated using the streptozotocin-induced hyperglycemia model. The ethyl acetate and petroleum ether fractions demonstrated a notable hypoglycemic impact in a rat model of type 2 diabetes mellitus (T2DM), compared to the negative control group. The chemical assessment of these fractions resulted in the isolation and identification of six known compounds (<b>17–22</b>). LC-HR-ESI-MS metabolomic profiling yielded the provisional identification of sixteen metabolites (<b>1–16</b>) across various chemical classes. In silico investigations, encompassing molecular docking and dynamics simulations, indicated that the compounds heterophylliin A (<b>22</b>), as well as habbemine A (<b>12</b>) and elaeocarpinoside (<b>15</b>), can interact with critical enzymes implicated in glucose metabolism, specifically dipeptidyl peptidase-IV and aldose reductase. Moreover, heterophylliin A (<b>22</b>) markedly decreased the expression of inflammatory markers (<i>IL-1β, TNF-α, IL-6</i>, and <i>TGF-β</i>) in diabetic rats. These findings prompt additional research on <i>E. grandis</i>, specifically its bioactive constituent heterophylliin A, which exhibits intriguing antidiabetic effects and warrants further exploration as a potential treatment agent for T2DM.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 10","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211120","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Inhibitory Effects of 3-Deoxysappanchalcone on Factor Xa Activity, Platelet Aggregation, and Experimentally Induced Thrombosis 3-脱氧参查尔酮对Xa因子活性、血小板聚集和实验性血栓形成的抑制作用。
IF 3.6 3区 医学
Archiv der Pharmazie Pub Date : 2025-10-03 DOI: 10.1002/ardp.70101
Jinhee Lee, Gyuri Han, Jong-Sup Bae
{"title":"Inhibitory Effects of 3-Deoxysappanchalcone on Factor Xa Activity, Platelet Aggregation, and Experimentally Induced Thrombosis","authors":"Jinhee Lee,&nbsp;Gyuri Han,&nbsp;Jong-Sup Bae","doi":"10.1002/ardp.70101","DOIUrl":"10.1002/ardp.70101","url":null,"abstract":"<div>\u0000 \u0000 <p>3-Deoxysappanchalcone (3-DSC), extracted from <i>Caesalpinia sappan</i> L., is recognized for its anti-inflammatory, anti-influenza, and anti-allergic effects, but its antithrombotic properties have not been investigated. This study explores whether 3-DSC exhibits antithrombotic effects and examines the mechanisms involved. The antithrombotic properties of 3-DSC were assessed through various methods, including tests for clotting times, platelet aggregation analysis, evaluation of factor Xa activity and production, nitric oxide levels, and the expression of related proteins. This study found that 3-DSC extended the clotting time in human platelet-poor plasma at levels comparable to rivaroxaban, a standard anticoagulant, and reduced platelet aggregation triggered by ADP or the thromboxane A2 analog U46619. Additionally, 3-DSC suppressed the phosphorylation of PLCγ2 and PKC, as well as intracellular calcium release, which are essential for platelet aggregation. It also decreased the expression of adhesion molecules P-selectin and PAC-1. Furthermore, 3-DSC promoted nitric oxide production while reducing endothelin-1 secretion in endothelial cells exposed to ADP or U46619. Lastly, it inhibited both the activity and production of coagulation factor Xa in endothelial cells and prevented activated factor X (FXa)-induced platelet aggregation. Injection of 3-DSC significantly shortened the time required for thrombus resolution, reduced the size and number of thrombi, and decreased mortality in mouse models of thromboembolism. The study demonstrates that 3-DSC effectively exhibits antithrombotic activity by prolonging the clotting time, inhibiting platelet aggregation, and reducing factor Xa activity, comparable to standard anticoagulants. These findings highlight the potential of 3-DSC as a promising therapeutic agent targeting multiple pathways involved in thrombosis, with reduced side effects.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 10","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145211122","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Issue Information: Arch Pharm (10/2025) 发行资料:大药房(10/2025)
IF 3.6 3区 医学
Archiv der Pharmazie Pub Date : 2025-10-03 DOI: 10.1002/ardp.70123
{"title":"Issue Information: Arch Pharm (10/2025)","authors":"","doi":"10.1002/ardp.70123","DOIUrl":"https://doi.org/10.1002/ardp.70123","url":null,"abstract":"","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 10","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145223803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
The Potential of Resveratrol as an Anticancer Agent: Updated Overview of Mechanisms, Applications, and Perspectives 白藜芦醇作为抗癌药物的潜力:机制、应用和前景的最新综述。
IF 3.6 3区 医学
Archiv der Pharmazie Pub Date : 2025-09-29 DOI: 10.1002/ardp.70109
Md Rezaul Islam, Rahaf Ajaj, Abdur Rauf, Sanzida Sharmin Shanta, Md Ibrahim Khalil Al-Imran, Md Naeem Hossain Fakir, Alessandra Gianoncelli, Giovanni Ribaudo
{"title":"The Potential of Resveratrol as an Anticancer Agent: Updated Overview of Mechanisms, Applications, and Perspectives","authors":"Md Rezaul Islam,&nbsp;Rahaf Ajaj,&nbsp;Abdur Rauf,&nbsp;Sanzida Sharmin Shanta,&nbsp;Md Ibrahim Khalil Al-Imran,&nbsp;Md Naeem Hossain Fakir,&nbsp;Alessandra Gianoncelli,&nbsp;Giovanni Ribaudo","doi":"10.1002/ardp.70109","DOIUrl":"10.1002/ardp.70109","url":null,"abstract":"<div>\u0000 \u0000 <p>The natural polyphenol resveratrol, found in several plants, has garnered significant interest due to its beneficial effects on health and for its potential anticancer properties. Studies have demonstrated that it can alter various signaling pathways linked to cancer development and that it inhibits tumor development and spread by exerting several antiproliferative, proapoptotic, anti-inflammatory, and antiangiogenic mechanisms. Its role in regulating oxidative stress and epigenetic modifications further enhances its therapeutic potential. Nevertheless, despite promising preclinical results, clinical translation is to some extent limited by bioavailability, metabolism, and dosage. This updated review explores the mechanisms, also from a structural point of view, behind the anticancer properties of resveratrol, focusing on its impact on crucial signaling networks in different cancer models. Additionally, it overviews the current limitations of resveratrol-based treatments and suggests potential improvements through innovative delivery methods, drug combination approaches, and development of new derivatives. This review was conceived as an update with respect to contributions already present in the literature, thus particular attention has been dedicated to the contribution reported in the literature within the last 5 years and to these studies reporting in vivo data.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184273","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Targeting JNK1/2 and P38 Mitogen-Activated Protein Kinases With Pazopanib Mitigates Bleomycin-Induced Lung Fibrosis 帕唑帕尼靶向JNK1/2和P38丝裂原活化蛋白激酶减轻博莱霉素诱导的肺纤维化。
IF 3.6 3区 医学
Archiv der Pharmazie Pub Date : 2025-09-28 DOI: 10.1002/ardp.70105
Rasha Abdelhady, Rabab H. Sayed, Nancy S. Younis, Omaima Ali, Mai Abdallah Elhemely, Ahmed M. Ashour, Shuruq E. Alsufyani, Hany H. Arab, Mohammed S. Abdel-Hamid
{"title":"Targeting JNK1/2 and P38 Mitogen-Activated Protein Kinases With Pazopanib Mitigates Bleomycin-Induced Lung Fibrosis","authors":"Rasha Abdelhady,&nbsp;Rabab H. Sayed,&nbsp;Nancy S. Younis,&nbsp;Omaima Ali,&nbsp;Mai Abdallah Elhemely,&nbsp;Ahmed M. Ashour,&nbsp;Shuruq E. Alsufyani,&nbsp;Hany H. Arab,&nbsp;Mohammed S. Abdel-Hamid","doi":"10.1002/ardp.70105","DOIUrl":"10.1002/ardp.70105","url":null,"abstract":"<p>Idiopathic pulmonary fibrosis is considered the most common type of interstitial lung disease. The principal aim of our research was to investigate the potential role of pazopanib treatment in alleviating bleomycin-elicited pulmonary fibrosis and elucidate the underlying molecular mechanisms. Twenty-four male mice were allocated into four groups (<i>n</i> = 6): control animals (received saline intraperitoneally (i.p.)), bleomycin group received bleomycin (40 U/kg, i.p.) on 5 days, 0, 3, 7, 10, and 14, and bleomycin and pazopanib-treated group received bleomycin on the specified days and then received pazopanib (10 mg/kg, i.p.) once daily starting on Day 15 to Day 28, plus pazopanib-treated group, which received pazopanib only in the previously specified dose and duration. Our results demonstrated the promising role of pazopanib in mitigating pulmonary fibrosis, as reflected by the remarkable improvement in body weight loss and pulmonary histopathological features. This finding was primarily ascribed to the documented suppression of mitogen-activated protein kinase kinase kinase 2 (MEKK2) and MEKK3 mRNA expressions, which subsequently repressed p-c-Jun N-terminal kinase (p-JNK1/2) and p-P38 group of protein kinases (p-P38) protein expressions. Moreover, pazopanib administration to bleomycin-treated mice remarkably adjusted the bleomycin-mediated dysregulation of the levels of examined cytokines, including interleukin (IL)-1β, IL-13, IL-33, tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa-B (NF-κB) P65. Remarkably, pazopanib treatment reversed the bleomycin-induced elevation in transforming growth factor-beta-1 (TGF-β1) and α-smooth muscle actin (α-SMA) levels. Our research highlighted the beneficial role of pazopanib in attenuating bleomycin-elicited lung fibrosis through the suppression of MEKK2 and MEKK3 and the modulation of JNK and P38 cascades.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12477462/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184239","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
New 1,3,4-Thiadiazole-Based Dual B-Raf/VEGFR-2 Inhibitors With Potential Anti-Breast Activity: Design, Synthesis, In Vitro and In Silico Evaluations 具有潜在抗乳腺活性的新型1,3,4-噻二唑类双B-Raf/VEGFR-2抑制剂:设计、合成、体外和计算机评价
IF 3.6 3区 医学
Archiv der Pharmazie Pub Date : 2025-09-28 DOI: 10.1002/ardp.70097
Walid E. Elgammal, Hazem Elkady, Hazem A. Mahdy, Bshra A. Alsfouk, Dalal Z. Husein, Fatma G. Amin, Abdelrahman A. Abuelkhir, Eslam B. Elkaeed, Ahmed M. Metwaly, Ibrahim H. Eissa
{"title":"New 1,3,4-Thiadiazole-Based Dual B-Raf/VEGFR-2 Inhibitors With Potential Anti-Breast Activity: Design, Synthesis, In Vitro and In Silico Evaluations","authors":"Walid E. Elgammal,&nbsp;Hazem Elkady,&nbsp;Hazem A. Mahdy,&nbsp;Bshra A. Alsfouk,&nbsp;Dalal Z. Husein,&nbsp;Fatma G. Amin,&nbsp;Abdelrahman A. Abuelkhir,&nbsp;Eslam B. Elkaeed,&nbsp;Ahmed M. Metwaly,&nbsp;Ibrahim H. Eissa","doi":"10.1002/ardp.70097","DOIUrl":"10.1002/ardp.70097","url":null,"abstract":"<div>\u0000 \u0000 <p>This study reports the design, synthesis, and biological evaluation of a novel series of 1,3,4-thiadiazole-based derivatives as dual B-Raf and VEGFR-2 kinase inhibitors with potential anticancer activity. Among the synthesized compounds, <b>7b</b> emerged as the most potent candidate, exhibiting strong cytotoxicity against the MDA-MB-231 and MCF-7 breast cancer cell lines (IC₅₀ = 9.66 and 15.83 µM, respectively), with minimal toxicity toward normal WI-38 and WISH cells, reflected by favorable selectivity indices. Compound <b>7b</b>, featuring a unique structural assembly of a 2,3-dihydro-1,3,4-thiadiazole core, a <i>para</i>-methoxyphenyl group, and a sulfonamide-linked methylpiperidine moiety, exhibited superior dual-inhibitory activity. It showed IC₅₀ values of 0.75 µM for B-Raf and 58.13 nM for VEGFR-2. Flow cytometry and gene expression analysis revealed that <b>7b</b> induces G1-phase cell-cycle arrest and promotes apoptosis through the upregulation of BAX, caspases-8/9, and downregulation of Bcl-2. Compound <b>7b</b> also inhibited cell migration in wound-healing assays. Structure–activity relationship (SAR) analysis indicated that <i>para</i>-substituted electron-donating groups enhanced cytotoxic potency. Molecular docking and molecular dynamics simulations confirmed the stable binding of <b>7b</b> to the kinase active sites, supported by favorable Glide scores (–25.47 kcal/mol for VEGFR-2 and –31.64 kcal/mol) and MM-GBSA (molecular mechanics with generalized Born and surface area solvation) binding energies. Density functional theory (DFT) calculations further validated the compound's electronic stability and reactivity. These integrated findings suggest that compound <b>7b</b> is a promising lead for further development as a selective dual kinase inhibitor for breast cancer therapy.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Synthesis, Biological Evaluation and Molecular Docking Studies of Novel 4-Propylsulfonylpiperazines-Based Thiosemicarbazones as Ecto-5′-Nucleotidase and NTPDase Inhibitors 新型4-丙基磺酰基哌嗪类硫代氨基脲类外5′-核苷酸酶和ntpase抑制剂的合成、生物学评价及分子对接研究
IF 3.6 3区 医学
Archiv der Pharmazie Pub Date : 2025-09-28 DOI: 10.1002/ardp.70098
Hina Aftab, Shireen Mona Dutt, Suraj N. Mali, Erica Vigiani, Julie Pelletier, Jean Sévigny, Shailesh S. Gurav, Rahul D. Jawarkar, Abdulraheem SA Almalki, Muhammad Safwan Akram, Zahra Batool, Silvia Schenone, Jamshed Iqbal, Zahid Shafiq
{"title":"Synthesis, Biological Evaluation and Molecular Docking Studies of Novel 4-Propylsulfonylpiperazines-Based Thiosemicarbazones as Ecto-5′-Nucleotidase and NTPDase Inhibitors","authors":"Hina Aftab,&nbsp;Shireen Mona Dutt,&nbsp;Suraj N. Mali,&nbsp;Erica Vigiani,&nbsp;Julie Pelletier,&nbsp;Jean Sévigny,&nbsp;Shailesh S. Gurav,&nbsp;Rahul D. Jawarkar,&nbsp;Abdulraheem SA Almalki,&nbsp;Muhammad Safwan Akram,&nbsp;Zahra Batool,&nbsp;Silvia Schenone,&nbsp;Jamshed Iqbal,&nbsp;Zahid Shafiq","doi":"10.1002/ardp.70098","DOIUrl":"10.1002/ardp.70098","url":null,"abstract":"<div>\u0000 \u0000 <p>Purinergic signaling is modulated by extracellular enzymes known as ectonucleotidases. Ecto-5′-nucleotidase and NTPDases are part of the ectonucleotidase family. NTPDases control ATP levels through hydrolysis, whereas ecto-5′-NT collaborates with NTPDase to break down nucleotide molecule. Due to their roles in inflammation, infection, and cancer, both enzymes present promising targets for therapeutic interventions. In this study, we present a novel and environment-friendly synthetic approach for the creation of small molecules that are not based on nucleotides, specifically substituted sulfonyl-piperazine-based thiosemicarbazone derivatives <b>7(a–s)</b>. We assessed their inhibitory effects on ecto-5′-nucleotidase and NTPDase1, 2, 3, and 8. Most of the compounds displayed excellent inhibition against one or more forms, while some displayed selective inhibition. To gain a deeper understanding of how the synthesized compounds interact with the isoenzymes, we conducted molecular docking studies. Additionally, ADME analyses were performed to predict the pharmacokinetic properties of these compounds. The integration of in vitro and in silico studies enabled the identification of compounds with potential inhibitory activity and favorable binding orientations. The observed results provide compelling evidence for the potency of the biologically active scaffold, sulfonylpiperazine, as a powerful and selective NTPDase inhibitor.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
In Vitro Modeling of the Antitumor Drugs Effects on the Endothelial Barrier Function 抗肿瘤药物对内皮屏障功能影响的体外模型研究。
IF 3.6 3区 医学
Archiv der Pharmazie Pub Date : 2025-09-28 DOI: 10.1002/ardp.70104
Aleksandra S. Churkina, Kseniya N. Sedenkova, Polina А. Kovaleva, Anton S. Shakhov, Anatoly A. Kotlobay, Elena B. Averina, Irina B. Alieva
{"title":"In Vitro Modeling of the Antitumor Drugs Effects on the Endothelial Barrier Function","authors":"Aleksandra S. Churkina,&nbsp;Kseniya N. Sedenkova,&nbsp;Polina А. Kovaleva,&nbsp;Anton S. Shakhov,&nbsp;Anatoly A. Kotlobay,&nbsp;Elena B. Averina,&nbsp;Irina B. Alieva","doi":"10.1002/ardp.70104","DOIUrl":"10.1002/ardp.70104","url":null,"abstract":"<div>\u0000 \u0000 <p>Pulmonary edema and acute respiratory failure, developing due to the vascular endothelium dysfunction, are common side effects of anticancer therapy. This study is the first approach to create an in vitro model system to estimate vascular response at the drug development/improvement stage and to determine whether it is possible to select an antitumor drug dose effectively suppressing malignant cells without a pathological effect on the endothelial cells function. In this study (1) the doses of several clinically used antitumor drugs suppressing the common tumor cell proliferation were determined experimentally; (2) the endothelial cell viability after exposure to selected doses of these drugs was assessed in vitro; (3) changes in the endothelial monolayer condition, as well as cultured endothelial cell reactions and intracellular disorders accompanying the effects of selected drugs doses were studied in vitro using the intravital observations and super-resolution microscopy methods. This approach allowed to select antitumor drug concentrations inhibiting cell proliferation in selected tumor lines, but having no critical effect on the viability of endothelial cells and their cytoskeletal structures. As the result, an in vitro model system for studying the side effects of medications on vascular permeability was created.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145184306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
Ultra-Fast Green UPLC-MS/MS Method for the Quantification of Cediranib in the Human Liver Microsome Matrix: In Vitro and In Silico Metabolic Stability Assessment 超快速绿色超高效液相色谱-质谱联用法定量人肝微粒体基质中Cediranib的体外和计算机代谢稳定性评价
IF 3.6 3区 医学
Archiv der Pharmazie Pub Date : 2025-09-27 DOI: 10.1002/ardp.70111
Mohamed W. Attwa, Ali S. Abdelhameed, Adnan A. Kadi
{"title":"Ultra-Fast Green UPLC-MS/MS Method for the Quantification of Cediranib in the Human Liver Microsome Matrix: In Vitro and In Silico Metabolic Stability Assessment","authors":"Mohamed W. Attwa,&nbsp;Ali S. Abdelhameed,&nbsp;Adnan A. Kadi","doi":"10.1002/ardp.70111","DOIUrl":"https://doi.org/10.1002/ardp.70111","url":null,"abstract":"<div>\u0000 \u0000 <p>Cediranib (AZD2171; CDB) is an oral pan-VEGF receptor tyrosine kinase inhibitor and a potent antiangiogenic agent. This study sought to develop a precise, rapid, dependable, and sustainable UPLC-MS/MS approach for measuring CDB in the human liver microsome (HLM) matrix, utilized for assessing the CDB metabolic stability inside this matrix. The validation processes for the UPLC-MS/MS system adhered to US-FDA rules for bioanalytical technique validation. The validated method utilized the HLM matrix throughout a level range of 1–4000 ng/mL with a duration of 1 min on UPLC-MS/MS instrumentation. The precision (%RSD) and accuracy (%E) rates for intraday and interday measurements varied from −1.41% to 8.0% and from −2.75% to 9.67%, respectively. The StarDrop software employed P450 and DEREK modules to evaluate metabolic lability and to characterize CDB structural warnings, respectively. The in vitro <i>t</i><sub>1/2</sub> was determined to be 25.48 min, and the CDB intrinsic clearance was determined to be 31.82 mL/min/kg. In silico assessments indicate that slight structural modifications to the pyrrolidine moiety (61%), methyl group (32%), and the propyl group (7%) in drug design could increase the CDB metabolic stability. The assessment of in silico CDB ADME characteristics and metabolic stability is fundamental for progressing innovative drug research focused on augmenting metabolic stability.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145146859","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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
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