Archiv der Pharmazie最新文献

Pyrazolopyridine-Containing Compounds as Multitargeted Anti-Alzheimer Agents: Synthesis, Biological Evaluation, and In Silico Studies 含吡唑吡啶的多靶点抗阿尔茨海默病药物：合成、生物学评价和计算机研究

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-06-22 DOI: 10.1002/ardp.70025

Omnia M. Waly, Selwan M. El-Sayed, Mariam A. Ghaly, Hussein I. El-Subbagh

{"title":"Pyrazolopyridine-Containing Compounds as Multitargeted Anti-Alzheimer Agents: Synthesis, Biological Evaluation, and In Silico Studies","authors":"Omnia M. Waly, Selwan M. El-Sayed, Mariam A. Ghaly, Hussein I. El-Subbagh","doi":"10.1002/ardp.70025","DOIUrl":"https://doi.org/10.1002/ardp.70025","url":null,"abstract":"<div>\u0000 \u0000 <p>Multitargeted directed ligands (MTDLs) represent an appealing tactic to treat Alzheimer's disease (AD) as a multifactorial neurodegenerative disorder. In this study, the pyrazolopyridine scaffold was used to design three different series of integrated MTDLs that could inhibit the main causes of AD. They possess common structure features essential for such a goal. The planar pyrazolopyridine core allows binding with the catalytically active site of cholinesterase enzymes and intercalating between the residues of Aβ and tau protein. In addition, the planar ring is attached to different linkers and hydrophobic side chains to prop interaction with the peripheral anionic site of AChE, preventing Aβ<sub>1-42</sub> aggregation. They also provide tools for binding with <i>h</i>GSK3β hydrophobic tails responsible for tau hyperphosphorylation and NFTs formation. Moreover, basic nitrogen atoms are also present, which chelate biometals, hindering their oxidative damage to the brain. Compounds <b>15</b> and <b>23</b> fulfilled all the mentioned anticipated activities. Furthermore, compound <b>31</b>, which is the possible metabolite of the ethyl ester <b>23</b>, appeared as MTDL, proving that compound <b>23</b> would have a long duration of action. Finally, compounds <b>15</b> and <b>23</b> exhibited a wide safety range upon WI-38 cell line, obeyed Lipinski's rule of five, and could virtually penetrate the blood–brain barrier.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339363","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

A Multifaceted Mechanistic Approach to Assess the Inhibitory Potential of Broccoli-Derived Glucosinolates Against Tumor-Associated Carbonic Anhydrase IX 评估西兰花衍生硫代葡萄糖苷对肿瘤相关碳酸酐酶IX的抑制潜力的多方面机制方法

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-06-22 DOI: 10.1002/ardp.70019

Emadeldin M. Kamel, Doaa A. Abdelrheem, Sarah I. Othman, Saleh Maodaa, Al Mokhtar Lamsabhi

{"title":"A Multifaceted Mechanistic Approach to Assess the Inhibitory Potential of Broccoli-Derived Glucosinolates Against Tumor-Associated Carbonic Anhydrase IX","authors":"Emadeldin M. Kamel, Doaa A. Abdelrheem, Sarah I. Othman, Saleh Maodaa, Al Mokhtar Lamsabhi","doi":"10.1002/ardp.70019","DOIUrl":"https://doi.org/10.1002/ardp.70019","url":null,"abstract":"<div>\u0000 \u0000 <p>Hypoxia-induced carbonic anhydrase IX (CA IX) is a clinically validated anticancer target; yet, few natural, isoform-selective inhibitors have been described. We isolated three glucosinolates—glucoraphanin, 1,4-dimethoxyglucobrassicin, and 4-methoxyglucobrassicin—from <i>Brassica oleracea</i> and interrogated their CA IX inhibitory potential through an integrated experimental-computational workflow. Enzyme assays revealed mixed-type inhibition with nanomolar potency (IC₅₀ = 65–221 nM), while counterscreens against housekeeping CA I/II demonstrated > 40-fold selectivity. Molecular docking, 500-ns molecular-dynamics simulations, free-energy-landscape mapping, and MM/PBSA calculations consistently ranked the ligands as 4-methoxyglucobrassicin > glucoraphanin > 1,4-dimethoxyglucobrassicin, attributing superior binding to deep hydrophobic insertion, persistent hydrogen bonding, and favorable van der Waals and electrostatic contributions (ΔG<sub>MM/PBSA</sub> = −25 kJ mol<sup>−1</sup>). In silico ADMET profiling indicated low hERG and CYP liabilities but flagged limited oral absorption and moderate hepatotoxicity, suggesting the need for targeted delivery or scaffold optimization. Collectively, these findings position 4-methoxyglucobrassicin as a promising natural-product lead for selective CA IX inhibition and provide a mechanistic framework for structure-guided analog design.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339365","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

DiWB-1: A Luteinizing Hormone Releasing Hormone (LHRH)-Targeted Peptide-Drug Conjugate (PDC) With Enhanced Tumor Selectivity and PI3K Inhibition Efficacy DiWB-1：一种促黄体生成素释放激素（LHRH）靶向肽-药物偶联物（PDC），具有增强的肿瘤选择性和PI3K抑制作用

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-06-22 DOI: 10.1002/ardp.70021

Chenyu Zhang, Honglan Zhong, Xiang Li, Zhenjian Xing, Siming Li, Rui Yu, Xin Deng

{"title":"DiWB-1: A Luteinizing Hormone Releasing Hormone (LHRH)-Targeted Peptide-Drug Conjugate (PDC) With Enhanced Tumor Selectivity and PI3K Inhibition Efficacy","authors":"Chenyu Zhang, Honglan Zhong, Xiang Li, Zhenjian Xing, Siming Li, Rui Yu, Xin Deng","doi":"10.1002/ardp.70021","DOIUrl":"https://doi.org/10.1002/ardp.70021","url":null,"abstract":"<div>\u0000 \u0000 <p>Phosphoinositide 3-kinase (PI3K) inhibitors have demonstrated efficacy in cancer therapy; yet, their clinical use is often restricted by off-target toxicity. Peptide-drug conjugates (PDCs) have emerged as a strategy to improve tumor selectivity by targeting receptors overexpressed in malignant cells. Luteinizing hormone-releasing hormone receptors (LHRHR), upregulated in several cancers, present an attractive target for such approaches. In this study, we obtained an LHRHR-targeting peptide IV-6, characterized by high receptor affinity and robust metabolic stability. IV-6 was then conjugated to the PI3K inhibitor buparlisib, forming the target PDC, DiWB-1. In Vitro, DiWB-1 exhibited superior antineoplastic effects against LHRHR-positive MDA-MB-231 cells, with an IC<sub>50</sub> of 1.8 μM, compared with 2.4 μM for buparlisib, and demonstrated reduced toxicity in normal cells. In Vivo, DiWB-1 showed considerable tumor-suppressive effects while minimizing systemic toxicity, avoiding the hepatic and renal damage, as well as hyperglycemia, observed with buparlisib treatment. Pharmacokinetic studies further indicated that DiWB-1 had favorable metabolic stability, with a half-life of 5.6 h, slightly exceeding that of triptorelin (4.2 h). These findings suggest that DiWB-1 holds promise as a selective, potent, and long-acting anticancer PDC, warranting further investigation.</p>\u0000 </div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339364","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

Orphan G Protein-Coupled Receptors: A Novel Research Frontier in Autism and Associated Disorders 孤儿G蛋白偶联受体：自闭症及相关疾病的新研究前沿

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-06-20 DOI: 10.1002/ardp.70018

Hanieh Gholamalizadeh, Vafa Baradaran Rahimi, Vahid Reza Askari

{"title":"Orphan G Protein-Coupled Receptors: A Novel Research Frontier in Autism and Associated Disorders","authors":"Hanieh Gholamalizadeh, Vafa Baradaran Rahimi, Vahid Reza Askari","doi":"10.1002/ardp.70018","DOIUrl":"https://doi.org/10.1002/ardp.70018","url":null,"abstract":"<div>\u0000 \u0000 <p>G-protein coupled receptors (GPCRs) are a diverse group of membrane proteins crucial for transmitting extracellular signals into cells, regulating numerous neurological processes. Among GPCRs, orphan receptors, whose natural ligands and functions remain unidentified, have garnered increasing research attention. Olfactory receptors (ORs), the most diverse GPCR family, are widely expressed in the central nervous system (CNS) and are implicated in autism spectrum disorder (ASD) and related behavioral and psychiatric conditions. This review highlights the altered expression of specific orphan and olfactory GPCRs—such as RORα, RORβ, GPR37, GPR62, OR1C1, and OR52M1—and their roles in ASD development. It explores their mechanisms of action, neural network interactions, and contributions to ASD etiology, as well as associated disorders like ADHD, schizophrenia, epilepsy, anxiety, depression, and sleep disorders. The review also addresses challenges in orphan GPCR research, such as identifying ligands and understanding their physiological roles, while emphasizing their potential as therapeutic targets. By summarizing preclinical and clinical findings, this review underscores the emerging significance of orphan receptors in ASD, offering a foundation for future research to advance understanding and develop innovative treatments for autism and related conditions.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323375","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

Hitting Two Birds With One Stone: Dual Modulation of Brain Carbonic Anhydrases and Histone Deacetylases Boosts Memory Consolidation 一箭双雕：脑碳酸酐酶和组蛋白去乙酰酶的双重调节促进记忆巩固

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-06-18 DOI: 10.1002/ardp.70020

Alessia Costa, Murat Bozdag, Gioele Renzi, Barbara Rani, Maria Beatrice Passani, Andrea Angeli, Gustavo Provensi, Fabrizio Carta, Claudiu T. Supuran

{"title":"Hitting Two Birds With One Stone: Dual Modulation of Brain Carbonic Anhydrases and Histone Deacetylases Boosts Memory Consolidation","authors":"Alessia Costa, Murat Bozdag, Gioele Renzi, Barbara Rani, Maria Beatrice Passani, Andrea Angeli, Gustavo Provensi, Fabrizio Carta, Claudiu T. Supuran","doi":"10.1002/ardp.70020","DOIUrl":"https://doi.org/10.1002/ardp.70020","url":null,"abstract":"<p>Cognitive impairments, characterized by deficits in one or more cognitive domains, are common in several pathological conditions but remain inadequately addressed by available pharmacological treatments. Given the complexity and multifaceted mechanisms underpinning these deficits, multi-targeted directed ligands are emerging as promising strategies for developing more effective therapies. In this study, we reported the design, synthesis as well as In Vitro and Ex Vivo assessment of prototypic molecular scaffolds that activate the carbonic anhydrase (CA; EC 4.2.1.1) and inhibit the histone deacetylase (HDAC; EC 3.5.1.98) metalloenzymes. By using the novel object recognition paradigm, we found that these compounds significantly enhanced memory consolidation at doses 10 times lower than single-target reference compounds. Taken together, these results suggest that the dual modulation of CA and HDAC activities by means of a single hybrid molecular entity represents an innovative approach for the management of cognitive symptoms associated with neurodegenerative, neurodevelopment, and psychiatric disorders.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.70020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144308869","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 Therapeutic Potential of Berberine in Lung Cancer 小檗碱治疗肺癌的潜力

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-06-09 DOI: 10.1002/ardp.70013

Zohreh Jafari, Shokouh Honarmand, Zeinab Abbasirad, Sahar Sadeghi, Ashkan Bigham

{"title":"The Therapeutic Potential of Berberine in Lung Cancer","authors":"Zohreh Jafari, Shokouh Honarmand, Zeinab Abbasirad, Sahar Sadeghi, Ashkan Bigham","doi":"10.1002/ardp.70013","DOIUrl":"https://doi.org/10.1002/ardp.70013","url":null,"abstract":"<div>\u0000 \u0000 <p>Lung cancer has the second-highest incidence rate after breast cancer and remains the leading cause of cancer-related mortality. The 1-year survival rate for lung cancer patients is below 50%, highlighting the urgent need for novel therapeutic strategies and drug development. Phytochemicals and their derivatives have been widely explored for their anticancer properties, serving as chemotherapeutic agents against various types of cancer. One of these herbal compounds, berberine (BBR), a quaternary isoquinoline alkaloid, has shown significant promise in preclinical studies and is currently undergoing clinical trials for cancer treatment. BBR exhibits diverse biological activities, contributing to its anticancer potential, including antioxidant, antidiarrheal, antidiabetic, antimicrobial, and so on. However, despite its multifunctional therapeutic potential, BBR faces several limitations, hindering its clinical application, like poor bioavailability, low tissue uptake, a short plasma half-life, and rapid metabolic elimination. To address these challenges, various targeted drug delivery approaches have been developed to improve its efficacy. This review aims to provide a comprehensive overview of drug delivery strategies designed to encapsulate BBR for enhanced lung cancer therapy, highlighting the most recent advancements in the field. Moreover, the molecular structure of BBR and the biological pathways it targets to inhibit lung cancer progression are discussed in detail. Finally, BBR-encapsulated nanocarriers specifically developed for lung cancer therapy are evaluated in terms of their benefits, limitations, and overall therapeutic potential.</p>\u0000 </div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 6","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144244153","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 (6/2025) 发行资料：大药房（6/2025）

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-06-09 DOI: 10.1002/ardp.70024

引用次数: 0

Aripiprazole as an Inhibitor of the EGFR/PI3K/AKT Signaling Pathway and Sensitizer of MPA Suppressed Progestin-Resistant Endometrial Cancer Cells 阿立哌唑作为EGFR/PI3K/AKT信号通路抑制剂和MPA抑制孕激素抵抗子宫内膜癌细胞的增敏剂

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-05-25 DOI: 10.1002/ardp.70017

Wen Gan, Xinyu Liu, Yikang Zhou, Wei Gu, Xiaohu Liu, Lingyi Song, Jian Li, Yudong Wang, Fei Mao

{"title":"Aripiprazole as an Inhibitor of the EGFR/PI3K/AKT Signaling Pathway and Sensitizer of MPA Suppressed Progestin-Resistant Endometrial Cancer Cells","authors":"Wen Gan, Xinyu Liu, Yikang Zhou, Wei Gu, Xiaohu Liu, Lingyi Song, Jian Li, Yudong Wang, Fei Mao","doi":"10.1002/ardp.70017","DOIUrl":"https://doi.org/10.1002/ardp.70017","url":null,"abstract":"<div>\u0000 \u0000 <p>Drug repurposing, which involves applying existing pharmaceuticals to new therapeutic areas, offers several advantages, including increased efficiency, reduced costs, and lower risks. The research aimed to investigate the molecular mechanisms underlying the new application of the antipsychotic drug aripiprazole (APZ) in the treatment of endometrial cancer (EC), as well as its synergistic efficacy when used in combination with progestin. The cell viability assay and proliferation assay demonstrated that APZ exerted a significant inhibitory effect on the proliferation of ISK and KLE cells. Moreover, APZ was found to induce cell apoptosis prominently by flow cytometry. Network pharmacology analysis indicated that the anti-EC effects of APZ were mediated via the epidermal growth factor receptor (EGFR)/phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway, which was subsequently confirmed by Western blot analysis. Furthermore, APZ significantly enhanced the proliferation inhibitory effect of medroxyprogesterone acetate (MPA) against progestin-resistant KLE cells, displaying remarkable synergistic activity. These findings position APZ as a promising therapeutic candidate for EC, with potential utility both as a monotherapy and in combination with MPA, offering new avenues for EC treatment strategies.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135640","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, Characterization and Evaluation of Antioxidant and Antimicrobial Activities of Novel Isatin Derivatives 新型Isatin衍生物的合成、表征及抗氧化抗菌活性评价

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-05-25 DOI: 10.1002/ardp.70014

Komal Rathi, Divya Kumari, Priyanka Yadav, Varun Rawat, Pracheta Janmeda, Ved Prakash Verma

{"title":"Synthesis, Characterization and Evaluation of Antioxidant and Antimicrobial Activities of Novel Isatin Derivatives","authors":"Komal Rathi, Divya Kumari, Priyanka Yadav, Varun Rawat, Pracheta Janmeda, Ved Prakash Verma","doi":"10.1002/ardp.70014","DOIUrl":"https://doi.org/10.1002/ardp.70014","url":null,"abstract":"<div>\u0000 \u0000 <p>The pursuit of multifunctional therapeutic agents remains crucial in combating oxidative stress and microbial resistance. In this study, we synthesized and characterized a diverse series of novel isatin-based derivatives (<b>12a–z</b>), exploring their antioxidant and antimicrobial potential. Notably, compound <b>12c</b> demonstrated remarkable antioxidant efficacy among all isatin-based derivatives, with an IC₅₀ value of 9.79 ± 0.168 µg/mL in the DPPH radical scavenging assay, positioning it as a potent radical scavenger comparable to the standard (ascorbic acid). Furthermore, antimicrobial screening identified compounds <b>12a</b> and <b>12b</b> as standout candidates, showcasing strong antibacterial and antifungal properties through disc-diffusion and broth dilution methods. These promising bioactivities underscore the potential of <b>12a</b>, <b>12b</b> and <b>12c</b> as therapeutic agents, meriting further investigation for their application in oxidative stress-related conditions and infectious disease management. This study lays the groundwork for future development of isatin derivatives as pharmacologically relevant molecules in both antioxidant and antimicrobial domains.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144135663","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

The Quest for Ligands Against Kinesin Motor Protein Eg5 寻找对抗运动蛋白Eg5的配体

IF 4.3 3区医学

Archiv der Pharmazie Pub Date : 2025-05-22 DOI: 10.1002/ardp.70010

Ahmet Fatih Sahin, Simone Carradori, Alessia Ricci, Muhammad Rashad, Atilla Akdemir

{"title":"The Quest for Ligands Against Kinesin Motor Protein Eg5","authors":"Ahmet Fatih Sahin, Simone Carradori, Alessia Ricci, Muhammad Rashad, Atilla Akdemir","doi":"10.1002/ardp.70010","DOIUrl":"https://doi.org/10.1002/ardp.70010","url":null,"abstract":"<div>\u0000 \u0000 <p>The Kinesin Eg5 motor protein is essential for the formation of the mitotic spindles and chromosome segregation, which is necessary for cell division. The inhibition of Eg5 has emerged as a potential therapeutic strategy for inhibiting the uncontrolled proliferation of cancer cells. This study aims to identify inhibitors targeting the allosteric site I of Eg5. To this end, a hierarchical virtual screening was applied to screen the ZINC20-Anodyne compound library comprising approximately 11 million druglike compounds. The procedure includes a shape similarity screening, a pharmacophore screening, docking studies with subsequent re-scorings, molecular dynamics simulations, and Molecular Mechanics-Generalized Born Surface Area (MM-GBSA) binding free energy calculations and resulted in the selection of four compounds for Eg5 inhibition assays. One compound displays an IC<sub>50</sub> value of 29 µM, while the remaining three compounds show weaker inhibition of Kinesin Eg5. As such, structurally novel Kinesin Eg5 inhibitors have been obtained for further hit-to-lead optimization programs.</p>\u0000 </div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 5","pages":""},"PeriodicalIF":4.3,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118020","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