Expert Opinion on Drug Discovery最新文献

New models for cancer cachexia and their application to drug discovery. 癌症恶病质的新模型及其在药物开发中的应用。

IF 4.9 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-10-03 DOI: 10.1080/17460441.2025.2562020

Ryosuke Sato, Markus S Anker, Jochen Springer, Stephan von Haehling

{"title":"New models for cancer cachexia and their application to drug discovery.","authors":"Ryosuke Sato, Markus S Anker, Jochen Springer, Stephan von Haehling","doi":"10.1080/17460441.2025.2562020","DOIUrl":"https://doi.org/10.1080/17460441.2025.2562020","url":null,"abstract":"Introduction: Cancer cachexia (CC) is a multifactorial syndrome characterized by progressive weight loss, anorexia, and loss of skeletal muscle and fat mass, resulting in reduced quality of life and poor prognosis. Currently, there are no approved pharmacological treatments for CC, highlighting the urgent need for developing novel experimental models.Area covered: This review covers recent advancements in preclinical models of CC, highlighting their implications for drug discovery and therapeutic development. The literature search was conducted in PubMed up to April 2025.Expert opinion: CC remains clinically challenging and requires improved translational research and therapeutic strategies. Improved preclinical models, such as personalized patient-derived xenograft models incorporating patient-specific immune profiles and microbiota, hold promise for precision medicine. Identification of standardized extracellular vesicle (EV) derived biomarkers and effective targeting of EV signaling pathways are critical research directions. In addition, clinical validation of appetite regulators such as glucagon-like peptide-1 and growth differentiation factor-15, along with comprehensive approaches integrating diet, exercise, and targeted pharmacological interventions, will be pivotal. Finally, multidisciplinary collaboration is essential to translate these findings into meaningful therapies that will ultimately improve patient prognosis and quality of life.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1-13"},"PeriodicalIF":4.9,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212085","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 discovery and development of tisagenlecleucel for the treatment of adult patients with relapsed or refractory follicular lymphoma. 用于治疗复发或难治性滤泡性淋巴瘤成人患者的tisagenlecleucel的发现和发展。

IF 4.9 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-10-02 DOI: 10.1080/17460441.2025.2567291

Smith Kungwankiattichai, Richard T Maziarz

{"title":"The discovery and development of tisagenlecleucel for the treatment of adult patients with relapsed or refractory follicular lymphoma.","authors":"Smith Kungwankiattichai, Richard T Maziarz","doi":"10.1080/17460441.2025.2567291","DOIUrl":"https://doi.org/10.1080/17460441.2025.2567291","url":null,"abstract":"Introduction: Follicular lymphoma (FL) is an indolent yet incurable subtype of non-Hodgkin lymphoma characterized by repeated relapses and diminishing responses with each treatment line. Although front-line chemoimmunotherapy achieves high initial response rates, a subset of patients - particularly those with early relapse (POD24) - experience poor outcomes and require alternative therapies. Tisagenlecleucel (tisa-cel), a CD19-directed chimeric antigen receptor (CAR) T-cell therapy, has emerged as a promising option for relapsed or refractory (r/r) FL, offering the potential for deep and durable remissions.Areas covered: This review covers the scientific rationale, preclinical innovations, and clinical development of tisa-cel, from its origins in 2nd-generation CAR-T engineering to its pivotal trials in hematologic malignancies. It is based on a literature search using PubMed, Embase, and conference abstracts from major hematology meetings from 1987 to April 2025. The paper deta ils the ELARA trial outcomes, subsequent long-term and real-world data, and the competitive landscape of third-line therapies for r/r FL.Expert opinion: Tisa-cel has demonstrated high response rates and sustained remissions with a favorable safety profile in heavily pretreated FL, including high-risk populations such as those with POD24. While bispecific antibodies offer convenient outpatient administration, CAR-T cell therapy provides the potential for deep and durable remissions. The 4-1BB costimulatory domain used in tisa-cel and liso-cel is associated with a lower incidence of severe CRS and ICANS compared to CD28-based constructs. the field evolves, careful patient selection and head-to-head trials will be essential to refine therapeutic sequencing in r/r FL.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1-12"},"PeriodicalIF":4.9,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145212088","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

Discovery of novel cathepsin K inhibitors for osteoporosis treatment using a deep learning-based strategy. 使用基于深度学习的策略发现用于骨质疏松症治疗的新型组织蛋白酶K抑制剂。

IF 4.9 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-10-01 Epub Date: 2025-07-02 DOI: 10.1080/17460441.2025.2527686

Qi Li, Xue-Chun Han, Si-Rui Zhou, Yu Lu, Yu-Ji Wang, Jin-Kui Yang

{"title":"Discovery of novel cathepsin K inhibitors for osteoporosis treatment using a deep learning-based strategy.","authors":"Qi Li, Xue-Chun Han, Si-Rui Zhou, Yu Lu, Yu-Ji Wang, Jin-Kui Yang","doi":"10.1080/17460441.2025.2527686","DOIUrl":"10.1080/17460441.2025.2527686","url":null,"abstract":"Background: Cathepsin K (CTSK), a cysteine protease of the papain family, exhibits high expression in activated osteoclasts, making it a key therapeutic target for osteoporosis. However, there are currently no CTSK inhibitors available for clinical use.Research design and methods: The authors employed a combination of deep learning approaches and experimental methods to identify novel CTSK inhibitors. Firstly, the authors utilized Chemprop to develop a predictive model for predicting CTSK inhibition. Subsequently, the top 100 predicted molecules were selected for experimental validation, with the most potent inhibitors chosen for further analysis, including enzyme kinetics, molecular docking, molecular dynamics simulations, and RANKL-induced osteoclastogenesis assays.Results: The authors identified six compounds exhibiting concentration-dependent CTSK inhibitory effects, with Quercetin, γ-Linolenic acid (GLA), and Benzyl isothiocyanate (BITC) demonstrating the highest potency. Enzyme kinetics studies revealed that these inhibitors employ distinct mechanisms of CTSK inhibition. Molecular dynamics simulations further showed that Quercetin and BITC form stable interactions at the CTSK active site. Moreover, in-vitro studies demonstrated that Quercetin and GLA significantly inhibit RANKL-induced osteoclastogenesis in RAW264.7 cells.Conclusions: This study led to the development of a deep learning model capable of predicting CTSK inhibitors and identified Quercetin, GLA, and BITC as promising candidates for the treatment of osteoporosis.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1345-1356"},"PeriodicalIF":4.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144539754","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 gepirone hydrochloride extended-release tablets: the first oral selective 5-HT1A receptor agonist for the treatment of major depressive disorder. 治疗重度抑郁症的口服选择性5-HT1A受体激动剂盐酸吉旋龙缓释片的临床前发现与开发

IF 4.9 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-10-01 Epub Date: 2025-09-01 DOI: 10.1080/17460441.2025.2552144

George Konstantakopoulos, Dionysios Argyropoulos, Antonis Tsionis

{"title":"The preclinical discovery and development of gepirone hydrochloride extended-release tablets: the first oral selective 5-HT1A receptor agonist for the treatment of major depressive disorder.","authors":"George Konstantakopoulos, Dionysios Argyropoulos, Antonis Tsionis","doi":"10.1080/17460441.2025.2552144","DOIUrl":"10.1080/17460441.2025.2552144","url":null,"abstract":"Introduction: Despite advances in antidepressant development, many patients with major depressive disorder (MDD) remain inadequately treated. Gepirone, a selective 5-HT1A agonist without reuptake inhibition, offers a novel mechanism potentially improving efficacy and tolerability over selective serotonin reuptake inhibitors (SSRIs) and earlier agents.Areas covered: This case history describes gepirone's discovery and development, including its pharmacodynamic profile, preclinical data on pharmacology, mechanism of action, and effects on depressive-like behavior and anxiety, as well as early clinical findings on its safety and efficacy in major depressive disorder. The review draws on English peer-reviewed articles and trials (1983-2025) from major databases, including PubMed, Embase, and ClinicalTrials.gov.Expert opinion: Although gepirone ER was approved due to evidence supporting clinical efficacy and favorable tolerability in MDD, its antidepressant effect size is modest relative to other monoamine-based antidepressants. It may offer particular benefit for patients who experience anxiety-related adverse effects on standard antidepressants and may be particularly useful in anxious depression or patients prioritizing tolerability. Approved by the U.S. Food and Drug Administration in 2023, withdrawn in 2024, the product will relaunch in late 2025. Future research should assess head-to-head efficacy, pharmacoeconomics, real-world outcomes, and its potential role in treatment-resistant depression.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1223-1237"},"PeriodicalIF":4.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948302","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

Artificial intelligence in drug design: why a 'one-size-fits-all' approach remains out of reach. 药物设计中的人工智能：为什么“一刀切”的方法仍然遥不可及。

IF 4.9 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-10-01 Epub Date: 2025-08-06 DOI: 10.1080/17460441.2025.2543802

Rafael Lopes Almeida, Gabriella Matos Campera, Ina Pöhner, Vinicius Gonçalves Maltarollo

{"title":"Artificial intelligence in drug design: why a 'one-size-fits-all' approach remains out of reach.","authors":"Rafael Lopes Almeida, Gabriella Matos Campera, Ina Pöhner, Vinicius Gonçalves Maltarollo","doi":"10.1080/17460441.2025.2543802","DOIUrl":"10.1080/17460441.2025.2543802","url":null,"abstract":"Introduction: Advances in artificial intelligence (AI) have transformed the drug design and discovery process, introducing novel methods that can reduce costs, increase success rates, and shorten development timelines. However, due to the complexity and multifactorial nature of this process, no single AI approach is likely to be universally effective.Areas covered: This review summarizes progress made over the past five years toward diverse drug development goals using AI tools. It also discusses the main challenges that inhibit the development and adoption of a broad AI solution in this field.Expert opinion: Despite major advancements, AI fails to reach its full potential due to issues related to data quality, model complexity, computational costs, and organizational barriers. At present, the effectiveness of any AI approach heavily depends on its application. Ultimately, while the world strives for a general-purpose AI, no method in drug discovery can yet be considered universally applicable, and rather than relying on a one-size-fits-all solution, individual trade-offs and research objectives need to be carefully aligned to harness AI's potential in drug discovery.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1239-1250"},"PeriodicalIF":4.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788579","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 advances in the development of promising carbohydrate-based therapeutics. 基于碳水化合物的治疗方法的最新进展。

IF 4.9 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-10-01 Epub Date: 2025-08-21 DOI: 10.1080/17460441.2025.2547890

Nayyar Ahmad Aslam, Yevhenii Kyriukha, James W Janetka

{"title":"Recent advances in the development of promising carbohydrate-based therapeutics.","authors":"Nayyar Ahmad Aslam, Yevhenii Kyriukha, James W Janetka","doi":"10.1080/17460441.2025.2547890","DOIUrl":"10.1080/17460441.2025.2547890","url":null,"abstract":"Introduction: Carbohydrates are ubiquitous biomolecules that play indispensable roles in living systems, functioning in cellular communication, genetic information storage, cellular energy provision, structural support, host-pathogen interactions, and the biosynthesis of secondary metabolites such as antibiotics. Their inherent multifunctionality, stereochemical complexity, and natural affinity for binding specific proteins make them highly attractive scaffolds for drug discovery. Despite their biological significance, carbohydrate-based therapeutics remain underrepresented in the pharmacopoeia, comprising only a small fraction of approved drugs. This underutilization highlights the untapped potential of carbohydrates as sources of novel therapeutic agents with innovative mechanisms of action.Areas covered: In this concise review, the authors summarize the current landscape of approved small-molecule drugs containing carbohydrate moieties and highlight recent advances in carbohydrate-based compounds with a wide spectrum of pharmacological activities, including antimicrobial, anticancer, antidiabetic, anti-inflammatory, neuroprotective, antiviral, and enzyme inhibitory effects.Expert opinion: Carbohydrate-based therapeutics are transitioning from niche applications to mainstream drug discovery platforms and, as such, hold significant promise for generating future generations of pharmaceuticals. Consequently, the authors firmly advocate continued efforts in designing carbohydrate-derived drug candidates which are well positioned to deliver first or best-in-class drugs.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1297-1326"},"PeriodicalIF":4.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144855038","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

How do drug discovery scientists address the unmet need of long COVID syndrome therapeutics and what more can be done? 药物发现科学家如何解决长期COVID综合征治疗的未满足需求？还可以做些什么？

IF 4.9 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-10-01 Epub Date: 2025-07-16 DOI: 10.1080/17460441.2025.2534056

Pasquale Pagliano, Flora Salzano, Chiara D'Amore, Annamaria Spera, Valeria Conti, Veronica Folliero, Gianluigi Franci, Tiziana Ascione

{"title":"How do drug discovery scientists address the unmet need of long COVID syndrome therapeutics and what more can be done?","authors":"Pasquale Pagliano, Flora Salzano, Chiara D'Amore, Annamaria Spera, Valeria Conti, Veronica Folliero, Gianluigi Franci, Tiziana Ascione","doi":"10.1080/17460441.2025.2534056","DOIUrl":"10.1080/17460441.2025.2534056","url":null,"abstract":"Introduction: Long COVID (LC), also known as post-acute COVID-19 syndrome (PASC), has emerged as a significant public health concern characterized by persistent symptoms following SARS-CoV-2 infection. This condition affects regardless of initial illness severity and can significantly impair daily functioning. Understanding the implications of LC is crucial, given that approximately 6.9 % of adults reported related symptoms in 2022, with increased prevalence among women and individuals of Hispanic descent. The pathogenesis of LC is multifactorial, involving mechanisms such as endothelial dysfunction, chronic inflammation, immune dysregulation, and potential viral persistence. The clinical manifestations include fatigue, cognitive impairment, musculoskeletal pain, and sleep disturbances. Current research emphasizes the importance of early antiviral interventions and vaccines to mitigate the risk of developing LC. Despite promising therapies like anti-inflammatory agents and metabolic enhancers, the lack of established biomarkers complicates diagnosis and treatment.Areas covered: The authors provide an overview of the pathogenesis of LC and briefly review the currently available therapy. The authors then give their perspectives on how best future drug discovery efforts can be utilized to address the current demand for novel LC therapeutics to reduce the burden of this public health problem.Expert opinion: Progress has been made in understanding the pathophysiology and potential treatment options, as well as in establishing reliable biomarkers for potential tailored strategies. Future research should prioritize both pharmacological and non-pharmacological interventions to enhance patient outcomes and quality of life. Addressing these challenges is essential for developing comprehensive care protocols for individuals affected by LC.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1251-1265"},"PeriodicalIF":4.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144636644","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 state of the art in dual-acting hybrid antibiotics to combat bacterial resistance. 对抗细菌耐药性的双作用混合抗生素的最新进展。

IF 4.9 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-10-01 Epub Date: 2025-09-11 DOI: 10.1080/17460441.2025.2552145

Alastair L Parkes, Oliver A Bardell-Cox, Ricky M Cain

{"title":"The state of the art in dual-acting hybrid antibiotics to combat bacterial resistance.","authors":"Alastair L Parkes, Oliver A Bardell-Cox, Ricky M Cain","doi":"10.1080/17460441.2025.2552145","DOIUrl":"10.1080/17460441.2025.2552145","url":null,"abstract":"Introduction: The efficacy of current treatments for bacterial infections is under threat due to the continuing rise in the prevalence of antimicrobial resistance (AMR). Resistance can arise due to a wide variety of changes in the bacterial cell that prevent the antibiotic from acting on its target. This can be through changes to the target itself or changes that limit access to the target. Strategies to overcome resistance therefore either seek to reestablish access to the target or to engage a different target for which resistance is yet to arise. This has been done successfully in the clinic through co-dosing of more than one molecule, but a long-held aim has been to achieve efficacy in a single 'hybrid' molecule.Areas covered: The authors review the progress since 2016 of hybrid antibiotics in clinical trials, cover some advances in preclinical research into dual-acting hybrids, and examine alternative approaches to using bi-functional hybrid molecules to tackle AMR.Expert opinion: Many contributory factors, both scientific and economic, have limited the success of dual-acting hybrids where both partners are antibiotics. The success of cefiderocol highlights the potential of linking molecules that target bacteria directly and non-antibiotics. These strategies offer some exciting possibilities.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1283-1295"},"PeriodicalIF":4.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948299","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

Advances in click chemistry for drug discovery and development. 药物发现和开发的点击化学进展。

IF 4.9 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-10-01 Epub Date: 2025-08-30 DOI: 10.1080/17460441.2025.2552146

Jiaojiao Dai, Xiaojia Xue, Xiangyi Jiang, Xinyong Liu, Peng Zhan

{"title":"Advances in click chemistry for drug discovery and development.","authors":"Jiaojiao Dai, Xiaojia Xue, Xiangyi Jiang, Xinyong Liu, Peng Zhan","doi":"10.1080/17460441.2025.2552146","DOIUrl":"10.1080/17460441.2025.2552146","url":null,"abstract":"Introduction: Click chemistry, first introduced by Sharpless and colleagues in 2001, has been an essential tool of drug research owing to its modularity, high efficiency, excellent yields, chemoselectivity, and mild reaction conditions.Areas covered: This review provides an overview of recent advances in drug development based on click chemistry over the past five years. It highlights key applications including fluorescent probes, lead identification and optimization, drug delivery systems, as well as emerging therapeutic modalities such as antibody-drug conjugates and protein degraders. The literature search was primarily conducted using PubMed and Web of Science.Expert opinion: Click chemistry serves as a powerful enabler of accelerated drug discovery and development. Nevertheless, its clinical translation faces challenges such as physiological interference, pharmacokinetic requirements, and the potential toxicity of metal catalysts. Going forward, research should prioritize optimizing click chemistry reactions to enhance biocompatibility, safety, and stability. Meanwhile, combining click chemistry with artificial intelligence offers promise for identifying structurally diverse candidate molecules that are also synthetically feasible.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1327-1343"},"PeriodicalIF":4.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948322","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

Phenotypic screening for new heart failure therapeutics: scalable animal modeling in zebrafish. 新型心力衰竭治疗的表型筛选：斑马鱼的可扩展动物模型。

IF 4.9 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-10-01 Epub Date: 2025-09-09 DOI: 10.1080/17460441.2025.2552148

Calum A MacRae

{"title":"Phenotypic screening for new heart failure therapeutics: scalable animal modeling in zebrafish.","authors":"Calum A MacRae","doi":"10.1080/17460441.2025.2552148","DOIUrl":"10.1080/17460441.2025.2552148","url":null,"abstract":"Introduction: Congestive heart failure (CHF) is a complex multi-organ syndrome representative of many chronic 'diseases,' and as such it has proven resistant to traditional cell-based drug discovery cannot readily be captured the relevant systemic biology. In vivo drug discovery screens offer unique opportunities to identify the initial dysfunction which ultimately drives heart failure (HF) and novel pathways modifying the cardiac response to injury.Areas covered: In this review, the author discusses phenotype-driven screens which allow rigorous and unbiased approaches to the biological systems which underpin HF (PubMed search terms on 07/11/2025-heart failure, cardiomyopathy, zebrafish, screen, drug). The rationale for specific models of HF and the relevance of the zebrafish in screens for suppressors of HF is discussed. Central principles are detailed for the successful design and execution of phenotypic screens for HF modifiers. A major focus is the development of scalable HF assays in the zebrafish.Expert opinion: In vivo phenotypic screening in the zebrafish is a reproducible approach to the identification of potent suppressors of complex multisystem disorders including different forms of HF. Design features associated with success are the rigor and human fidelity of the initial mechanistic modeling and quantitative screen endpoints.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1267-1282"},"PeriodicalIF":4.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144948363","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