Expert Opinion on Drug Discovery最新文献_第6页

The ongoing challenge of slowing ageing through drug discovery. 通过药物发现延缓衰老的持续挑战。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-04-01 Epub Date: 2025-03-24 DOI: 10.1080/17460441.2025.2482063

David G Le Couteur, Stephen J Simpson, Victoria C Cogger, Janani Thillainadesan, Rozalyn Anderson, Rafael de Cabo

引用次数: 0

The application of snake venom in anticancer drug discovery: an overview of the latest developments. 蛇毒在抗癌药物研发中的应用：最新进展综述。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-02-26 DOI: 10.1080/17460441.2025.2465364

Joana R da Silva, Juliana Castro-Amorim, Ashis K Mukherjee, Maria João Ramos, Pedro A Fernandes

{"title":"The application of snake venom in anticancer drug discovery: an overview of the latest developments.","authors":"Joana R da Silva, Juliana Castro-Amorim, Ashis K Mukherjee, Maria João Ramos, Pedro A Fernandes","doi":"10.1080/17460441.2025.2465364","DOIUrl":"https://doi.org/10.1080/17460441.2025.2465364","url":null,"abstract":"Introduction: Snake venom is a rich source of toxins with great potential for therapeutic applications. In addition to its efficacy in treating hypertension, acute coronary syndrome, and other heart conditions, research has shown that this potent enzymatic cocktail is capable of selectively targeting and destroying cancer cells in many cases while sparing healthy cells.Areas covered: The authors begin by acknowledging the emerging trends in snake-derived targeted therapies in battling cancer. An extensive literature review examining the effects of various snake venom toxins on cancer cell lines, highlighting the specific cancer hallmarks each toxin targets is presented. Furthermore, the authors emphasize the emerging potential of artificial intelligence in accelerating snake venom-based drug discovery for cancer treatment, showcasing several innovative software applications in this field.Expert opinion: Research on snake venom toxins indicates promising potential for cancer treatment as many of the discussed toxins can specifically target cancer cells. Nevertheless, variations in the composition of venoms, ethical issues, and delivery barriers limit their development into effective therapies. Thus, advances in biotechnology, molecular engineering, in silico methods are crucial for the refinement of venom-derived compounds, improving their specificity, and overcoming these challenges, ultimately enhancing their therapeutic potential in cancer therapy.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1-19"},"PeriodicalIF":6.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143515052","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 of chronic obstructive pulmonary disease and their role in drug discovery and development: a critical review. 慢性阻塞性肺疾病动物模型及其在药物发现和开发中的作用：综述

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-02-24 DOI: 10.1080/17460441.2025.2466704

Maria Gabriella Matera, Luigino Calzetta, Barbara Rinaldi, Vito de Novellis, Clive P Page, Peter J Barnes, Mario Cazzola

{"title":"Animal models of chronic obstructive pulmonary disease and their role in drug discovery and development: a critical review.","authors":"Maria Gabriella Matera, Luigino Calzetta, Barbara Rinaldi, Vito de Novellis, Clive P Page, Peter J Barnes, Mario Cazzola","doi":"10.1080/17460441.2025.2466704","DOIUrl":"10.1080/17460441.2025.2466704","url":null,"abstract":"Introduction: The use of laboratory animals is essential to understand the mechanisms underlying COPD and to discover and evaluate new drugs. However, the complex changes associated with the disease in humans are difficult to fully replicate in animal models.Areas covered: This review examines the most recent literature on animal models of COPD and their implications for drug discovery and development.Expert opinion: Recent advances in animal models include the introduction of transgenic mice with an increased propensity to develop COPD-associated features, such as emphysema, and animals exposed to relevant environmental agents other than cigarette smoke, in particular biomass smoke and other air pollutants. Other animal species, including zebrafish, pigs, ferrets and non-human primates, are also increasingly being used to gain insights into human COPD. Furthermore, three-dimensional organoids and humanized mouse models are emerging as technologies for evaluating novel therapeutics in more human-like models. However, despite these advances, no model has yet fully captured the heterogeneity and progression of COPD as observed in humans. Therefore, further research is needed to develop improved models incorporating humanized elements in experimental animals, that may better predict therapeutic responses in clinic settings and accelerate the development of new treatments for this debilitating disease.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1-20"},"PeriodicalIF":6.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406029","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

High performance-oriented computer aided drug design approaches in the exascale era. 百亿亿次时代的高性能计算机辅助药物设计方法。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-02-20 DOI: 10.1080/17460441.2025.2468289

Andrea Rizzi, Davide Mandelli

{"title":"High performance-oriented computer aided drug design approaches in the exascale era.","authors":"Andrea Rizzi, Davide Mandelli","doi":"10.1080/17460441.2025.2468289","DOIUrl":"10.1080/17460441.2025.2468289","url":null,"abstract":"Introduction: In 2023, the first exascale supercomputer was opened to the public in the US. With a demonstrated 1.1 exaflops of performance, Frontier represents an unprecedented breakthrough in high-performance computing (HPC). Currently, more (and more powerful) machines are being installed worldwide. Computer-aided drug design (CADD) is one of the fields of computational science that can greatly benefit from exascale computing for the benefit of the whole society. However, scaling CADD approaches to exploit exascale machines require new algorithmic and software solutions.Areas covered: Here, the authors consider physics-based and machine learning (ML)-aided techniques for the design of small molecule binders capable of leveraging modern parallel computer architectures. Specifically, the authors focus on HPC-oriented large-scale applications from the past 3 years that were enabled by (pre)exascale supercomputers by running on up tothousands of accelerated nodes.Expert opinion: In the area of ML, exascale computers can enable the training of generative models with unprecedented predictive power to design novel ligands, provided large amounts of high-quality data are available. Exascale computers could also unlock the potential of accurate ML-aided physics-based methods to boost the success rate of structure-based drug design campaigns. Currently, however, methodological developments are still required to allow routine large-scale applications of such rigorous approaches.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1-10"},"PeriodicalIF":6.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425440","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

Current challenges and future perspectives of drug discovery in China. 中国药物发现的当前挑战和未来展望。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-02-19 DOI: 10.1080/17460441.2025.2468290

Wei Han, Qingtong Zhou, Ming-Wei Wang

{"title":"Current challenges and future perspectives of drug discovery in China.","authors":"Wei Han, Qingtong Zhou, Ming-Wei Wang","doi":"10.1080/17460441.2025.2468290","DOIUrl":"10.1080/17460441.2025.2468290","url":null,"abstract":"Introduction: China's pharmaceutical industry, which is historically centered around generic medicines, has largely transformed from imitation to innovation over the past three decades. Despite unprecedented progress, critical challenges remain such as insufficient indigenous research funding, underdeveloped academia-industry relationships, and significant barriers to market access.Areas covered: This perspective examines the evolving pharmaceutical landscape of China, focusing on its participation in global clinical trials and the resultant new drug approvals. Data for this analysis was sourced from several databases (e.g. PharmCube, NextPharma, and PharmaGO), academic reports, and published literature, covering data up to 2024 (unless otherwise specified). This perspective highlights ongoing regulatory challenges, such as inconsistencies in product standards, and the approval processes relative to the U.S.A. and the European Union. There is also an urgent demand for sustained international investment and recognition, partially due to the recent changes in the geopolitical environment. This perspective also discusses China's efforts to implement accelerated approval pathways and foster multilateral development collaborations.Expert opinion: China must align its regulatory policies more closely to the international norm to generate robust trial data that will be readily acceptable to the FDA and EMA. Continued investment in biologics as well as cell and gene therapy and artificial intelligence will drive innovation and enhance competitiveness. Additionally, strengthening the academia-industry collaboration is crucial to obtaining new leads through translational research. Ultimately, structural reforms are required to solidify the country's goal of becoming a major player in the global pharmaceutical market.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1-10"},"PeriodicalIF":6.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425439","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 animal models of bladder cancer and their application in drug discovery: an update of the literature. 膀胱癌动物模型及其在药物发现中的应用：文献更新。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-02-17 DOI: 10.1080/17460441.2025.2465373

Inês Aires, Belmiro Parada, Rita Ferreira, Paula A Oliveira

{"title":"Recent animal models of bladder cancer and their application in drug discovery: an update of the literature.","authors":"Inês Aires, Belmiro Parada, Rita Ferreira, Paula A Oliveira","doi":"10.1080/17460441.2025.2465373","DOIUrl":"10.1080/17460441.2025.2465373","url":null,"abstract":"Introduction: Bladder cancer presents a significant health problem worldwide, with environmental and genetic factors contributing to its incidence. Histologically, it can be classified as carcinoma in situ, non-muscle invasive and muscle-invasive carcinoma, each one with distinct genetic alterations impacting prognosis and response to therapy. While traditional transurethral resection is commonly performed in carcinoma in situ and non-muscle invasive carcinoma, it often fails to prevent recurrence or progression to more aggressive phenotypes, leading to the frequent need for additional treatment such as intravesical chemotherapy or immunotherapy. Despite the advances made in recent years, treatment options for bladder cancer are still lacking due to the complex nature of this disease. So, animal models may hold potential for addressing these limitations, because they not only allow the study of disease progression but also the evaluation of therapies and the investigation of drug repositioning.Areas covered: This review discusses the use of animal models over the past decade, highlighting key discoveries and discussing advantages and disadvantages for new drug discovery.Expert opinion: Over the past decade animal models have been employed to evaluate new mechanisms underlying the responses to standard therapies, aiming to optimize bladder cancer treatment. The authors propose that molecular engineering techniques and AI may hold promise for the future development of more precise and effective targeted therapies in bladder cancer.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1-21"},"PeriodicalIF":6.0,"publicationDate":"2025-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143424430","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

Finding a needle in the haystack: ADME and pharmacokinetics/pharmacodynamics characterization and optimization toward orally available bifunctional protein degraders. 大海捞针：ADME和药代动力学/药效学表征和优化对口服双功能蛋白质降解。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-02-16 DOI: 10.1080/17460441.2025.2467195

Giulia Apprato, Giulia Caron, Gauri Deshmukh, Diego Garcia-Jimenez, Robin Thomas Ulrich Haid, Andy Pike, Andreas Reichel, Caroline Rynn, Zhang Donglu, Matthias Beat Wittwer

{"title":"Finding a needle in the haystack: ADME and pharmacokinetics/pharmacodynamics characterization and optimization toward orally available bifunctional protein degraders.","authors":"Giulia Apprato, Giulia Caron, Gauri Deshmukh, Diego Garcia-Jimenez, Robin Thomas Ulrich Haid, Andy Pike, Andreas Reichel, Caroline Rynn, Zhang Donglu, Matthias Beat Wittwer","doi":"10.1080/17460441.2025.2467195","DOIUrl":"https://doi.org/10.1080/17460441.2025.2467195","url":null,"abstract":"Introduction: Degraders are an increasingly important sub-modality of small molecules as illustrated by an ever-expanding number of publications and clinical candidate molecules in human trials. Nevertheless, their preclinical optimization of ADME and PK/PD properties has remained challenging. Significant research efforts are being directed to elucidate underlying principles and to derive rational optimization strategies.Areas covered: In this review the authors summarize current best practices in terms of in vitro assays and in vivo experiments. Furthermore, the authors collate and comment on the current understanding of optimal physicochemical characteristics and their impact on absorption, distribution, metabolism and excretion properties including the current knowledge of Drug-Drug interactions. Finally, the authors describe the Pharmacokinetic prediction and Pharmacokinetic/Pharmacodynamic -concepts unique to degraders and how to best implement these in research projects.Expert opinion: Despite many recent advances in the field, continued research will further our understanding of rational design regarding degrader optimization. Machine-learning and computational approaches will become increasingly important once larger, more robust datasets become available. Furthermore, tissue-targeting approaches (particularly regarding the Central Nervous System will be increasingly studied to elucidate efficacious drug regimens that capitalize on the catalytic mode of action. Finally, additional specialized approaches (e.g. covalent degraders, LOVdegs) can enrich the field further and offer interesting alternative approaches.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":""},"PeriodicalIF":6.0,"publicationDate":"2025-02-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143432786","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 zanubrutinib for the treatment of chronic lymphocytic leukemia. 扎鲁替尼治疗慢性淋巴细胞白血病的临床前发现和开发。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-02-13 DOI: 10.1080/17460441.2025.2465365

Teri K Schleicher, Melanie Cohen, Solomon A Graf

{"title":"The preclinical discovery and development of zanubrutinib for the treatment of chronic lymphocytic leukemia.","authors":"Teri K Schleicher, Melanie Cohen, Solomon A Graf","doi":"10.1080/17460441.2025.2465365","DOIUrl":"10.1080/17460441.2025.2465365","url":null,"abstract":"Introduction: The history of treating chronic lymphocytic leukemia (CLL) inflected in 2014 with the Food and Drug Administration's (FDA) approval of ibrutinib, the first-in-class small molecule inhibitor of the Bruton's tyrosine kinase (BTK). Zanubrutinib is a 2nd generation covalent BTK inhibitor developed and manufactured by BeiGene.Areas covered: In this review, the authors trace the arc of zanubrutinib development from the preclinical phase through the two landmark phase 3 studies in the CLL space, ALPINE and SEQUOIA. The authors cover contemporary management strategies in CLL and highlight the areas of need that zanubrutinib was designed to mitigate.Expert opinion: Zanubrutinib entered a fray of novel, exciting therapies for CLL. As the second of two 2nd generation covalent BTK inhibitors its path to prominence in CLL management was narrow. Emphasis during development on kinase selectivity and enhanced bioavailability identified a molecule with superior efficacy and tolerability; hierarchical endpoints in trial design allowed for efficient acquisition of comparative data. Zanubrutinib is endorsed by the National Comprehensive Cancer Network as a preferred, category 1 recommended treatment choice for CLL. Future efforts in combination therapies and response-directed treatment breaks will hopefully lead to still further improvements in use.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1-14"},"PeriodicalIF":6.0,"publicationDate":"2025-02-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143374047","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 rules often neglected in current medicinal chemistry. 在目前的药物化学中经常被忽视的规律。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-02-12 DOI: 10.1080/17460441.2025.2465370

Boris Cvek

引用次数: 0

Investigating novel pharmacological strategies for treatment-resistant depression: focus on new mechanisms and approaches. 研究治疗难治性抑郁症的新药理学策略：关注新的机制和方法。

IF 6 2区医学

Expert Opinion on Drug Discovery Pub Date : 2025-02-03 DOI: 10.1080/17460441.2025.2460674

Aline Silva de Miranda, Eliana C B Toscano, Venugopal Reddy Venna, Frederico Guilherme Graeff, Antonio Lucio Teixeira

{"title":"Investigating novel pharmacological strategies for treatment-resistant depression: focus on new mechanisms and approaches.","authors":"Aline Silva de Miranda, Eliana C B Toscano, Venugopal Reddy Venna, Frederico Guilherme Graeff, Antonio Lucio Teixeira","doi":"10.1080/17460441.2025.2460674","DOIUrl":"10.1080/17460441.2025.2460674","url":null,"abstract":"Introduction: A substantial number of patients exhibit treatment-resistant depression (TRD), posing significant challenges to clinicians. The discovery of novel molecules or mechanisms that may underlie TRD pathogenesis and antidepressant actions is highly needed.Areas covered: Using the PubMed database, the authors searched for emerging evidence of novel approaches for TRD based on experimental and human studies. Herein, the authors discuss the mechanisms underlying glutamatergic antagonists, modulators of the opioid system, and tryptamine-derivate psychedelics as well as the emerging platforms to investigate novel pharmacological targets for TRD. A search for clinical trials investigating novel agents and interventions for TRD was also conducted.Expert opinion: The understanding of the multiple pathophysiological mechanisms involved in TRD may add further value to the effective treatment, contributing to a more personalized approach. Esketamine was approved for the treatment of TRD and novel drugs with rapid antidepressant actions such as psilocybin and buprenorphine have also been investigated as potential therapeutic strategies. Over the past decades, technological advances such as omics approaches have broadened our knowledge regarding molecular and genetic underpinnings of complex conditions like TRD. Omics approaches could open new avenues for investigating glial-mediated mechanisms, including their crosstalk with neurons, as therapeutic targets in TRD.","PeriodicalId":12267,"journal":{"name":"Expert Opinion on Drug Discovery","volume":" ","pages":"1-15"},"PeriodicalIF":6.0,"publicationDate":"2025-02-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143064851","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