Expert Opinion on Drug Discovery最新文献

筛选
英文 中文
The value of coimmunoprecipitation (Co-IP) assays in drug discovery. 共免疫沉淀法(Co-IP)在药物发现中的价值。
IF 6 2区 医学
Expert Opinion on Drug Discovery Pub Date : 2025-07-01 Epub Date: 2025-04-28 DOI: 10.1080/17460441.2025.2497913
Zhongtian Cai, Danni Wang, Zekun Li, Mingxiao Gu, Qidong You, Lei Wang
{"title":"The value of coimmunoprecipitation (Co-IP) assays in drug discovery.","authors":"Zhongtian Cai, Danni Wang, Zekun Li, Mingxiao Gu, Qidong You, Lei Wang","doi":"10.1080/17460441.2025.2497913","DOIUrl":"10.1080/17460441.2025.2497913","url":null,"abstract":"<p><strong>Introduction: </strong>Co-IP assays are well-established technologies widely applicated for investigating the mechanisms underlying protein-protein interactions and identifying protein-protein interaction modulators. These assays play an important role in elucidating the complex networks of protein interactions critical for cellular functions.</p><p><strong>Areas covered: </strong>This review covers a technical protocol of standard Co-IP. The research contents and conclusions of Co-IP in protein-protein interactions and protein-protein interaction modulators are summarized. Finally, three derivations of Co-IP assays are introduced. Literature was surveyed from original publications, standard sources, PubMed and clinical trials through 14 April 2025.</p><p><strong>Expert opinion: </strong>To perform Co-IP successfully, researchers must consider the selection of specific antibody, remission of nonspecific binding and detection limitations for transient or weak interactions. Co-IP assays offer several advantages over tandem affinity purification and pull-down methods, particularly in their applicability to primary cells. This allows for the study of PPIs in a natural cellular environment. Conventional Co-IP assays often struggle to detect weak or transient interactions and can suffer from nonspecific binding contamination. However, advancements in Co-IP techniques address these challenges, enhancing sensitivity and specificity, and enabling the detection of subtle interactions while distinguishing specific binding events. This makes Co-IP a powerful tool for exploring the dynamics of protein interactions in living systems.</p>","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"859-872"},"PeriodicalIF":6.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143981022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
On the application of artificial intelligence in virtual screening. 人工智能在虚拟筛选中的应用研究。
IF 6 2区 医学
Expert Opinion on Drug Discovery Pub Date : 2025-07-01 Epub Date: 2025-05-25 DOI: 10.1080/17460441.2025.2508866
Thanawat Thaingtamtanha, Rahul Ravichandran, Francesco Gentile
{"title":"On the application of artificial intelligence in virtual screening.","authors":"Thanawat Thaingtamtanha, Rahul Ravichandran, Francesco Gentile","doi":"10.1080/17460441.2025.2508866","DOIUrl":"10.1080/17460441.2025.2508866","url":null,"abstract":"<p><strong>Introduction: </strong>Artificial intelligence (AI) has emerged as a transformative tool in drug discovery, particularly in virtual screening (VS), a crucial initial step in identifying potential drug candidates. This article highlights the significance of AI in revolutionizing both ligand-based virtual screening (LBVS) and structure-based virtual screening (SBVS) approaches, streamlining and enhancing the drug discovery process.</p><p><strong>Areas covered: </strong>The authors provide an overview of AI applications in drug discovery, with a focus on LBVS and SBVS approaches utilized in prospective cases where new bioactive molecules were identified and experimentally validated. Discussion includes the use of AI in quantitative structure-activity relationship (QSAR) modeling for LBVS, as well as its role in enhancing SBVS techniques such as molecular docking and molecular dynamics simulations. The article is based on literature searches on studies published up to March 2025.</p><p><strong>Expert opinion: </strong>AI is rapidly transforming VS in drug discovery, by leveraging increasing amounts of experimental data and expanding its scalability. These innovations promise to enhance efficiency and precision across both LBVS and SBVS approaches, yet challenges such as data curation, rigorous and prospective validation of new models, and efficient integration with experimental methods remain critical for realizing AI's full potential in drug discovery.</p>","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"845-857"},"PeriodicalIF":6.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144101617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Generative AI and digital twins: shaping a paradigm shift from precision to truly personalized medicine. 生成式人工智能和数字双胞胎:塑造从精准医疗到真正个性化医疗的范式转变。
IF 6 2区 医学
Expert Opinion on Drug Discovery Pub Date : 2025-07-01 Epub Date: 2025-05-23 DOI: 10.1080/17460441.2025.2507376
Maria Bordukova, Alina J Arneth, Nikita Makarov, Robyn M Brown, Elena K Schneider-Futschik, Shyamali C Dharmage, Elif Ekinci, Peter J Crack, Danny M Hatters, Alastair G Stewart, David Stroud, Teresa Sadras, Gary P Anderson, Fabian Schmich, Raul Rodriguez-Esteban, Michael P Menden
{"title":"Generative AI and digital twins: shaping a paradigm shift from precision to truly personalized medicine.","authors":"Maria Bordukova, Alina J Arneth, Nikita Makarov, Robyn M Brown, Elena K Schneider-Futschik, Shyamali C Dharmage, Elif Ekinci, Peter J Crack, Danny M Hatters, Alastair G Stewart, David Stroud, Teresa Sadras, Gary P Anderson, Fabian Schmich, Raul Rodriguez-Esteban, Michael P Menden","doi":"10.1080/17460441.2025.2507376","DOIUrl":"10.1080/17460441.2025.2507376","url":null,"abstract":"","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"821-826"},"PeriodicalIF":6.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144077045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Novel antibiotic discovery and the antibiotic resistome. 新抗生素的发现和抗生素抵抗组。
IF 6 2区 医学
Expert Opinion on Drug Discovery Pub Date : 2025-07-01 Epub Date: 2025-05-21 DOI: 10.1080/17460441.2025.2490838
Rustam Aminov
{"title":"Novel antibiotic discovery and the antibiotic resistome.","authors":"Rustam Aminov","doi":"10.1080/17460441.2025.2490838","DOIUrl":"10.1080/17460441.2025.2490838","url":null,"abstract":"<p><strong>Introduction: </strong>The success of antibiotics in the therapy of infectious diseases is overshadowed by almost inevitable emergence and dissemination of resistances toward these agents, which results in higher morbidity and mortality rates and increased costs. New strategies are now needed to both limit the risk of resistance and to discover new drugs that are efficacious.</p><p><strong>Areas covered: </strong>This review investigates the resistance problems through evolutionary lenses to better understand and potentially design improved therapeutics for infectious diseases. Furthermore, it gives an overview of the evolutionary history of antibiotic resistance genes and antibiotic biosynthesis genes/clusters, the structures of natural resistomes, and the regulatory roles of antibiotics. The author utilized ScienceDirect, PubMed, Web of Science and Google Scholar using the article's keywords and their combinations to retrieve the most relevant and up-to-date information.</p><p><strong>Expert opinion: </strong>Antibiotics and their corresponding resistances are ancient phenomena with their evolutionary timescales measured over a vast amount of time. Humans have also benefitted from access to, and the use of, a diverse range of antibiotics for many years also but have disrupted the balance by producing and using enormous amounts of antibiotics that have not existed before in natural ecosystems. This selective pressure has resulted in a tremendous expansion of resistomes. Future antibiotic discovery and development may need to pivot from exploiting extant antibiotic scaffolds and bacterial targets to reduce the risk of the rapid emergence of resistance from existing resistomes.</p>","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"927-941"},"PeriodicalIF":6.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 developments in the utilization of pyridones as privileged scaffolds in drug discovery. 吡啶酮在药物开发中的特殊支架应用的最新进展。
IF 6 2区 医学
Expert Opinion on Drug Discovery Pub Date : 2025-07-01 Epub Date: 2025-05-25 DOI: 10.1080/17460441.2025.2507377
Zheyu Li, Wenbo Ma, Linghui Gu, Jiayuan Xie, Kui Yang, Shibo Lin
{"title":"Recent developments in the utilization of pyridones as privileged scaffolds in drug discovery.","authors":"Zheyu Li, Wenbo Ma, Linghui Gu, Jiayuan Xie, Kui Yang, Shibo Lin","doi":"10.1080/17460441.2025.2507377","DOIUrl":"10.1080/17460441.2025.2507377","url":null,"abstract":"<p><strong>Introduction: </strong>Pyridones are six-membered, nitrogen-containing heterocycles, possessing two isomeric forms; these are 2-pyridones and 4-pyridones. Both pyridone rings display unique physicochemical properties including weak alkalinity and dual hydrogen-bond donor/acceptor propensities. These heterocyclic compounds are particularly underlined for their diverse biological effects, including their cytotoxicity activity as well as their antibacterial, antiviral, anti-inflammatory, and anti-fibrotic properties. This versatility has attracted remarkable interest and held promise for addressing the challenges of drug resistance.</p><p><strong>Area covered: </strong>This review is the outcome of literature searches conducted on articles published between 2022 and 2025 across several major databases, including PubMed, Scopus, and Web of Science, using specific keywords concerning 'pyridone' and 'bioactivity.' It focuses on the identification of therapeutic targets, the process of molecular mechanisms, and the plausible modes of interaction and binding.</p><p><strong>Expert opinion: </strong>Pyridones have been reported to exhibit a wide range of bioactivities by regulating critical signaling pathways that have a diverse influence on downstream gene expression, intracellular enzyme activity and cytoskeletal configuration. They are consequently used as privileged fragments in the design of biologically active molecules with promising application value in pharmaceutical chemistry. Further investigation will be required to enhance drug-like properties. Continuous progress in structure optimization and clinical trial results will help to provide a guideline for future drug candidate discovery.</p>","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"873-889"},"PeriodicalIF":6.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144136161","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Small-molecule inhibitors in psoriasis: medicinal chemistry insights. 银屑病的小分子抑制剂:药物化学见解。
IF 6 2区 医学
Expert Opinion on Drug Discovery Pub Date : 2025-07-01 Epub Date: 2025-05-20 DOI: 10.1080/17460441.2025.2507767
Tianqi Mao, Jingjing Gao, Jie Jia, Fengxia Zou, Kai Wang, Yiyun Wang, Jiyu Li, Tao Shen, Huanqiu Li
{"title":"Small-molecule inhibitors in psoriasis: medicinal chemistry insights.","authors":"Tianqi Mao, Jingjing Gao, Jie Jia, Fengxia Zou, Kai Wang, Yiyun Wang, Jiyu Li, Tao Shen, Huanqiu Li","doi":"10.1080/17460441.2025.2507767","DOIUrl":"10.1080/17460441.2025.2507767","url":null,"abstract":"<p><strong>Introduction: </strong>Psoriasis is a prevalent and widespread chronic immune disease and i s impacted by several variables. Although various medicines with diverse modes of operation have been licensed for the medical management of psoriasis, the ongoing investigation into its pathophysiological mechanisms, along with challenges related to administration and cost, has led to the increasing preference for new small molecule medications, namely janus kinase (JAK) and phosphodiesterase 4 (PDE4) inhibitors, in systemic therapy research.</p><p><strong>Areas covered: </strong>This review takes a medicinal chemistry perspective to comprehensively explore the development as psoriasis therapy targets for small molecule inhibitors of JAK and PDE4. We describe the chemical space explored by medicinal chemists from 2010 to 2024, with particular emphasis on the importance of inhibitors with diverse scaffolds in studies of selectivity, potency and binding modes.</p><p><strong>Expert opinion: </strong>Advancements in psoriasis treatment have shifted focus toward small-molecule drugs, such as JAK and PDE4 inhibitors, which offer advantages over biologics, including oral administration, improved cost-effectiveness, and reduced immunogenicity. Structural optimization based on receptor proteins and combination therapies further enhance drug performance and safety. Preclinical and clinical studies indicate that these strategies hold promise for developing more targeted, safer, and more effective treatments for psoriasis.</p>","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"891-912"},"PeriodicalIF":6.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Animal models for development of anti-obesity drugs in the age of GLP-1 agents. GLP-1药物时代抗肥胖药物开发的动物模型
IF 6 2区 医学
Expert Opinion on Drug Discovery Pub Date : 2025-07-01 Epub Date: 2025-05-21 DOI: 10.1080/17460441.2025.2507766
Alexander Culver, Keith Stayrook, Michele Comerota, Adrian Oblak, Thomas Burris
{"title":"Animal models for development of anti-obesity drugs in the age of GLP-1 agents.","authors":"Alexander Culver, Keith Stayrook, Michele Comerota, Adrian Oblak, Thomas Burris","doi":"10.1080/17460441.2025.2507766","DOIUrl":"10.1080/17460441.2025.2507766","url":null,"abstract":"<p><strong>Introduction: </strong>Obesity is a major health crisis globally, with prevalence escalating significantly in recent decades. Obesity is not merely excessive weight but is associated with myriad health complications. Ensuring the translational effectiveness of pre-clinical obesity models is paramount, and the success of GLP-1 therapies has highlighted important benchmarks for guiding drug development.</p><p><strong>Areas covered: </strong>The authors discuss the status of various animal models used for the development of anti-obesity drugs, with particular emphasis on rodent models and their validity of preclinical-to-clinical translation. They also highlight innovative animal model integration opportunities between obesity and other associated pathology. The article is based on literature searches using PubMed for content (up until February 2025).</p><p><strong>Expert opinion: </strong>The effectiveness of GLP-1 therapies in treating type 2 diabetes and obesity presents an opportunity to evaluate the translational relevance of animal models of obesity. Due to their compelling safety profiles, GLP-1(s) are being tested in a wide range of obesity-associated diseases. Optimization of the mechanistic qualities in this drug class requires the incorporation of new endpoints beyond body weight, including lean mass preservation, cardiovascular health, and anti-inflammatory activities. Finally, we are compelled by the intersection of non-obesity disease models into an obesogenic framework to understand the combinatorial effects of obesity on these other disease indications, including heart failure, neurodegenerative diseases, and cancer.</p>","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"913-925"},"PeriodicalIF":6.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144086066","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 latest advances with natural products in drug discovery and opportunities for the future: a 2025 update. 天然产物在药物发现和未来机遇方面的最新进展:2025年更新。
IF 6 2区 医学
Expert Opinion on Drug Discovery Pub Date : 2025-07-01 Epub Date: 2025-06-05 DOI: 10.1080/17460441.2025.2507382
Shaowen Xie, Fangyi Zhan, Jingjie Zhu, Shengtao Xu, Jinyi Xu
{"title":"The latest advances with natural products in drug discovery and opportunities for the future: a 2025 update.","authors":"Shaowen Xie, Fangyi Zhan, Jingjie Zhu, Shengtao Xu, Jinyi Xu","doi":"10.1080/17460441.2025.2507382","DOIUrl":"10.1080/17460441.2025.2507382","url":null,"abstract":"<p><strong>Introduction: </strong>The landscape of drug discovery is rapidly evolving, with natural products (NPs) playing a pivotal role in the development of novel therapeutics. Despite their historical significance, challenges persist in fully harnessing their potential in the development of modern medicine.</p><p><strong>Areas covered: </strong>This perspective discusses the recent advances and opportunities in NP-based drug discovery. This includes exploration of the recently approved representative NP-derived drugs, innovative target identification strategies and advancements in hybrid NP molecules for addressing complex diseases. Moreover, the authors also discuss the role of NP-derived payloads in antibody-drug conjugates (ADCs) for targeted cancer therapy. This article is based on searches using the FDA and DrugBank database as well the Derwent Innovations Index from Web of Science between the period of 2017 to 2025.</p><p><strong>Expert opinion: </strong>NPs remain vital to drug discovery, demonstrating adaptability in tackling complex medical challenges. Future efforts should focus on integrating advanced methodologies, such as artificial intelligence (AI), high-throughput screening, chemical biology, bioinformatics, gene regulation, the highly accurate non-labeling chemical proteomics approach to explore novel NPs targets. Emphasizing these developments will be crucial for maximizing the therapeutic potential of NPs in combating unmet medical needs.</p>","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"827-843"},"PeriodicalIF":6.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144110437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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-silico guided identification and in-vitro studies of potential FFAR4 agonists for type 2 diabetes mellitus therapy. 用于2型糖尿病治疗的潜在FFAR4激动剂的计算机引导鉴定和体外研究
IF 6 2区 医学
Expert Opinion on Drug Discovery Pub Date : 2025-06-28 DOI: 10.1080/17460441.2025.2522896
Divya Jhinjharia, Pinky Juneja, Gaurava Srivastava, Kiran Bharat Lokhande, Aarti Sharma, Jitendra Singh Rathore, Savneet Kaur, Shakti Sahi
{"title":"In-silico guided identification and <i>in-vitro</i> studies of potential FFAR4 agonists for type 2 diabetes mellitus therapy.","authors":"Divya Jhinjharia, Pinky Juneja, Gaurava Srivastava, Kiran Bharat Lokhande, Aarti Sharma, Jitendra Singh Rathore, Savneet Kaur, Shakti Sahi","doi":"10.1080/17460441.2025.2522896","DOIUrl":"https://doi.org/10.1080/17460441.2025.2522896","url":null,"abstract":"<p><strong>Background: </strong>The activation of free fatty acid receptor 4 (FFAR4) enhances insulin sensitivity and glucose uptake while mitigating inflammation. It is a promising therapeutic approach for managing type 2 diabetes mellitus (T2DM).</p><p><strong>Research design and methods: </strong>Structure and Ligand-based screening approaches were employed to evaluate 1.1 million molecules for FFAR4 agonistic activity. Eight promising candidates were selected based on their binding affinity, non-bonded interactions, and pharmacokinetic properties and subjected to 500 ns molecular dynamics simulations (MDS). The therapeutic efficacy of compounds was assessed through in vitro assays, including cell viability tests, glucose uptake analysis, and gene expression profiling.</p><p><strong>Results: </strong>The analysis revealed several residues (VAL98, ARG99, ARG183, ARG22, ARG24, GLU43, and TRP305) that are essential for biological activity. Insights into the mechanistic contribution of amino acid residues located in the extracellular and intracellular loops of FFAR4 to ligand binding were obtained through MDS analysis. The binding energy values indicate a stronger binding affinity between the FFAR4 and hit molecules. In vitro experiments on selected compounds (Comp35, CompN1, CompN2, and diosmetin) confirmed their potential effects on insulin-stimulated glucose uptake, IR, inflammation, and diabetic pathways.</p><p><strong>Conclusions: </strong>Comp35, diosmetin, CompN1, and CompN2 were found to be potential hit agonists and can be developed for therapy.</p>","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1-18"},"PeriodicalIF":6.0,"publicationDate":"2025-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144527107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 preclinical discovery and development of upadacitinib for the treatment of Crohn's disease. 用于治疗克罗恩病的upadacitinib的临床前发现和开发。
IF 6 2区 医学
Expert Opinion on Drug Discovery Pub Date : 2025-06-27 DOI: 10.1080/17460441.2025.2522890
Sophie Vieujean, Silvio Danese, Laurent Peyrin-Biroulet
{"title":"The preclinical discovery and development of upadacitinib for the treatment of Crohn's disease.","authors":"Sophie Vieujean, Silvio Danese, Laurent Peyrin-Biroulet","doi":"10.1080/17460441.2025.2522890","DOIUrl":"https://doi.org/10.1080/17460441.2025.2522890","url":null,"abstract":"<p><strong>Introduction: </strong>The JAK-STAT pathway plays a pivotal role in immune regulation and is implicated in the pathogenesis of Crohn's disease (CD). Upadacitinib is a JAK inhibitor with greater selectivity for JAK1 over JAK2 and JAK3, and is emerging as a promising alternative to biologic therapies in CD.</p><p><strong>Areas covered: </strong>A literature search of MEDLINE and EMBASE up to February 2025 was conducted using defined keywords to identify preclinical, clinical, and real-world studies on upadacitinib in CD. In early trials, upadacitinib demonstrated efficacy in reducing proinflammatory cytokines, improving intestinal barrier integrity, and achieving high intracellular drug concentrations in target tissues. The phase II CELEST trial demonstrated that upadacitinib induced both endoscopic and clinical responses in patients with moderate-to-severe CD. Subsequent phase III studies (U-EXCEED, U-EXCEL, U-ENDURE) confirmed rapid clinical remission, sustained efficacy, and a manageable safety profile, leading to regulatory approval. The efficacy and safety of this molecule in CD have been confirmed by real-world studies.</p><p><strong>Expert opinion: </strong>The currently available data suggests that upadacitinib is an effective oral therapy for CD, offering an alternative to biologics with predictable pharmacokinetics, rapid symptom relief, and sustained long-term benefits. Future research will refine its role in treatment algorithms, biomarker-driven personalization, and combination therapies.</p>","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1-21"},"PeriodicalIF":6.0,"publicationDate":"2025-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144505301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
相关产品
×
本文献相关产品
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信