发布求助
文献互助 智能选刊 最新文献

Drug Discovery Today最新文献

筛选
英文 中文
Regulatory readiness to facilitate the appropriate use of innovation in clinical trials: The case of decentralized clinical trial approaches 为促进在临床试验中适当利用创新做好监管准备：分散式临床试验方法
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-09-14 DOI: 10.1016/j.drudis.2024.104180
Amos J. de Jong , Mira G.P. Zuidgeest , Yared Santa-Ana-Tellez , Anthonius de Boer , Helga Gardarsdottir , the Trials@Home Consortium
{"title":"Regulatory readiness to facilitate the appropriate use of innovation in clinical trials: The case of decentralized clinical trial approaches","authors":"Amos J. de Jong ,&nbsp;Mira G.P. Zuidgeest ,&nbsp;Yared Santa-Ana-Tellez ,&nbsp;Anthonius de Boer ,&nbsp;Helga Gardarsdottir ,&nbsp;the Trials@Home Consortium","doi":"10.1016/j.drudis.2024.104180","DOIUrl":"10.1016/j.drudis.2024.104180","url":null,"abstract":"<div><div>Methodological and operational clinical trial innovation is needed to address key challenges associated with clinical trials, including limited generalizability and (s)low recruitment rates. In this article, we discuss how appropriate implementation of innovative clinical trial approaches can be facilitated by a timely identification of, and response to, emerging situations and innovation by regulators (i.e. regulatory readiness) using decentralized clinical trial (DCT) approaches – in which trial activities are moved closer to participants and away from the investigative sites – as a case study example. Specifically, we discuss how explorative research (e.g. using regulatory sandboxes) can enable the collection of data on the usefulness of DCT approaches. Additionally, we argue that DCT approaches should be evaluated similarly to conventional clinical trials.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104180"},"PeriodicalIF":6.5,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1359644624003052/pdfft?md5=54070be5f10ff3de1fbc2a29a874ccde&pid=1-s2.0-S1359644624003052-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Expression, regulation, and function of PD-L1 on non-tumor cells in the tumor microenvironment 肿瘤微环境中非肿瘤细胞上 PD-L1 的表达、调节和功能
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-09-13 DOI: 10.1016/j.drudis.2024.104181
Lingrong Hu , Chengliang Sun , Kai Yuan , Peng Yang
{"title":"Expression, regulation, and function of PD-L1 on non-tumor cells in the tumor microenvironment","authors":"Lingrong Hu ,&nbsp;Chengliang Sun ,&nbsp;Kai Yuan ,&nbsp;Peng Yang","doi":"10.1016/j.drudis.2024.104181","DOIUrl":"10.1016/j.drudis.2024.104181","url":null,"abstract":"<div><div>Antiprogrammed death ligand 1 (PD-L1) therapy is a leading immunotherapy, but only some patients with solid cancers benefit. Overwhelming evidence has revealed that PD-L1 is expressed on various immune cells in the tumor microenvironment (TME), including macrophages, dendritic cells, and regulatory T cells, modulating tumor immunity and influencing tumor progression. PD-L1 can also be located on tumor cell membranes as well as in exosomes and cytoplasm. Accordingly, the dynamic expression and various forms of PD-L1 might explain the therapy’s limited efficacy and resistance. Herein a systematic summary of the expression of PD-L1 on different immune cells and their regulatory mechanisms is provided to offer a solid foundation for future studies.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104181"},"PeriodicalIF":6.5,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258639","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
MicroRNAs and therapeutic potentials in acute and chronic cardiac disease 急性和慢性心脏病中的微 RNA 和治疗潜力
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-09-12 DOI: 10.1016/j.drudis.2024.104179
Rui Song, Lubo Zhang
{"title":"MicroRNAs and therapeutic potentials in acute and chronic cardiac disease","authors":"Rui Song,&nbsp;Lubo Zhang","doi":"10.1016/j.drudis.2024.104179","DOIUrl":"10.1016/j.drudis.2024.104179","url":null,"abstract":"<div><p>microRNAs (miRNAs) are small regulatory RNAs implicated in various cardiac disorders. In this review, the role of miRNAs is discussed in relation to acute myocardial infarction and chronic heart failure. In both settings, miRNAs are altered, contributing to injury and adverse remodeling. Notably, miRNA profiles differ between acute ischemic injury and progressive heart failure. Owing to miRNA variabilities between disease stages and delivery difficulties, translation of animal studies to the clinic remains challenging. The identification of distinct miRNA signatures could lead to the development of miRNA therapies tailored to different disease stages. Here, we summarize the current understanding of miRNAs in acute and chronic cardiac diseases, identify knowledge gaps and discuss progress in developing miRNA-based treatment strategies.</p></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104179"},"PeriodicalIF":6.5,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1359644624003040/pdfft?md5=0a00fedfa19b4c6cd48de16392cfbb81&pid=1-s2.0-S1359644624003040-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258640","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Targeted protein degradation: current molecular targets, localization, and strategies 靶向蛋白质降解：当前的分子靶点、定位和策略
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-09-12 DOI: 10.1016/j.drudis.2024.104178
Dimanthi Pliatsika, Cindy Blatter, Rainer Riedl
{"title":"Targeted protein degradation: current molecular targets, localization, and strategies","authors":"Dimanthi Pliatsika,&nbsp;Cindy Blatter,&nbsp;Rainer Riedl","doi":"10.1016/j.drudis.2024.104178","DOIUrl":"10.1016/j.drudis.2024.104178","url":null,"abstract":"<div><div>Targeted protein degradation (TPD) has revolutionized drug discovery by selectively eliminating specific proteins within and outside the cellular context. Over the past two decades, TPD has expanded its focus beyond well-established targets, exploring diverse proteins beyond cancer-related ones. This evolution extends the potential of TPD to various diseases. Notably, TPD can target proteins at demanding locations, such as the extracellular matrix (ECM) and cellular membranes, presenting both opportunities and challenges for future research. In this review, we comprehensively examine the exciting opportunities in the burgeoning field of TPD, highlighting different targets, their cellular environment, and innovative strategies for modern drug discovery.</div></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104178"},"PeriodicalIF":6.5,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Clinical strategies with antibody–drug conjugates as potential modifications for virotherapy 将抗体药物共轭物作为病毒疗法潜在改良剂的临床策略
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-09-11 DOI: 10.1016/j.drudis.2024.104165
Zi-Xian Liao , Po-Hsiang Huang , Shan-hui Hsu , Hsiung-Hao Chang , Chi-Heng Chang , S.-Ja Tseng
{"title":"Clinical strategies with antibody–drug conjugates as potential modifications for virotherapy","authors":"Zi-Xian Liao ,&nbsp;Po-Hsiang Huang ,&nbsp;Shan-hui Hsu ,&nbsp;Hsiung-Hao Chang ,&nbsp;Chi-Heng Chang ,&nbsp;S.-Ja Tseng","doi":"10.1016/j.drudis.2024.104165","DOIUrl":"10.1016/j.drudis.2024.104165","url":null,"abstract":"<div><p>The ability to selectively target cancer cells makes antibody–drug conjugates (ADCs) promising therapeutic options. They have been tested in clinical trials as a vehicle for tumor-specific delivery of cytotoxic payloads for a range of cancers. However, systemic administration of oncolytic virotherapy is challenging, because only a small portion of injected viruses reach the target. Despite the approval of higher viral doses, most viruses still end up in the liver, potentially causing toxicity in that organ. Integrating ADCs with virotherapy in the form of antibody–virus conjugates or virus–drug conjugates can potentially overcome these challenges and improve therapeutic outcomes.</p></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104165"},"PeriodicalIF":6.5,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142258641","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
Embryonic and larval zebrafish models for the discovery of new bioactive compounds against tuberculosis 用于发现抗结核新生物活性化合物的胚胎和幼体斑马鱼模型。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-09-07 DOI: 10.1016/j.drudis.2024.104163
Stella S. Antunes , Gabriel Forn-Cuní , Nelilma C. Romeiro , Herman P. Spaink , Fons J. Verbeek , Michelle F. Muzitano
{"title":"Embryonic and larval zebrafish models for the discovery of new bioactive compounds against tuberculosis","authors":"Stella S. Antunes ,&nbsp;Gabriel Forn-Cuní ,&nbsp;Nelilma C. Romeiro ,&nbsp;Herman P. Spaink ,&nbsp;Fons J. Verbeek ,&nbsp;Michelle F. Muzitano","doi":"10.1016/j.drudis.2024.104163","DOIUrl":"10.1016/j.drudis.2024.104163","url":null,"abstract":"<div><p>Tuberculosis (TB) is a world health challenge the treatment of which is impacted by the rise of drug-resistant strains. Thus, there is an urgent need for new antitubercular compounds and novel approaches to improve current TB therapy. The zebrafish animal model has become increasingly relevant as an experimental system. It has proven particularly useful during early development for aiding TB drug discovery, supporting both the discovery of new insights into mycobacterial pathogenesis and the evaluation of therapeutical toxicity and efficacy <em>in vivo</em>. In this review, we summarize the past two decades of zebrafish–<em>Mycobacterium marinum</em> research and discuss its contribution to the field of bioactive antituberculosis therapy development.</p></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104163"},"PeriodicalIF":6.5,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152810","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
P-glycoprotein (P-gp)-driven cancer drug resistance: biological profile, non-coding RNAs, drugs and nanomodulators P-糖蛋白（P-gp）驱动的癌症耐药性：生物学概况、非编码 RNA、药物和纳米调节剂。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-09-07 DOI: 10.1016/j.drudis.2024.104161
Yang Guo , Milad Ashrafizadeh , Murtaza M. Tambuwala , Jun Ren , Gorka Orive , Guiping Yu
{"title":"P-glycoprotein (P-gp)-driven cancer drug resistance: biological profile, non-coding RNAs, drugs and nanomodulators","authors":"Yang Guo ,&nbsp;Milad Ashrafizadeh ,&nbsp;Murtaza M. Tambuwala ,&nbsp;Jun Ren ,&nbsp;Gorka Orive ,&nbsp;Guiping Yu","doi":"10.1016/j.drudis.2024.104161","DOIUrl":"10.1016/j.drudis.2024.104161","url":null,"abstract":"<div><p>Drug resistance has compromised the efficacy of chemotherapy. The dysregulation of drug transporters including P-glycoprotein (P-gp) can mediate drug resistance through drug efflux. In this review, we highlight the role of P-gp in cancer drug resistance and the related molecular pathways, including phosphoinositide 3-kinase (PI3K)–Akt, phosphatase and tensin homolog (PTEN) and nuclear factor-κB (NF-κB), along with non-coding RNAs (ncRNAs). Extracellular vesicles secreted by the cells can transport ncRNAs and other proteins to change P-gp activity in cancer drug resistance. P-gp requires ATP to function, and the induction of mitochondrial dysfunction or inhibition of glutamine metabolism can impair P-gp function, thus increasing chemosensitivity. Phytochemicals, small molecules and nanoparticles have been introduced as P-gp inhibitors to increase drug sensitivity in human cancers.</p></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104161"},"PeriodicalIF":6.5,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152811","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
Collaborative GSK–University of Strathclyde doctoral research and training programmes: Transforming approaches to industry–academia engagement 葛兰素史克公司与斯特拉思克莱德大学的合作博士研究和培训计划：转变产学合作方式。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-09-07 DOI: 10.1016/j.drudis.2024.104162
Laura C. Paterson , Philip G. Humphreys , Henry A. Kelly , William J. Kerr
{"title":"Collaborative GSK–University of Strathclyde doctoral research and training programmes: Transforming approaches to industry–academia engagement","authors":"Laura C. Paterson ,&nbsp;Philip G. Humphreys ,&nbsp;Henry A. Kelly ,&nbsp;William J. Kerr","doi":"10.1016/j.drudis.2024.104162","DOIUrl":"10.1016/j.drudis.2024.104162","url":null,"abstract":"<div><p>A global biopharma company, GSK, and the University of Strathclyde have developed an expansive and transformative research and training partnership originating in chemistry-aligned disciplines, with subsequent extensive expansion across further areas of the company. This has opened unique approaches for the delivery of collaborative research innovations while also enhancing the professional development and learning of GSK personnel, in addition to other embedded researchers and collaborating scientists, on a pathway towards more rapid and efficient discovery of new medicines.</p></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104162"},"PeriodicalIF":6.5,"publicationDate":"2024-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S1359644624002873/pdfft?md5=684af4e4b7ff730912e2bd4dc063439b&pid=1-s2.0-S1359644624002873-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152809","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 pharmaceutical productivity gap – Incremental decline in R&D efficiency despite transient improvements 制药生产率差距--研发效率虽有短暂提高，但仍在逐步下降。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-09-05 DOI: 10.1016/j.drudis.2024.104160
Kenneth D.S. Fernald, Philipp C. Förster, Eric Claassen, Linda H.M. van de Burgwal
{"title":"The pharmaceutical productivity gap – Incremental decline in R&D efficiency despite transient improvements","authors":"Kenneth D.S. Fernald,&nbsp;Philipp C. Förster,&nbsp;Eric Claassen,&nbsp;Linda H.M. van de Burgwal","doi":"10.1016/j.drudis.2024.104160","DOIUrl":"10.1016/j.drudis.2024.104160","url":null,"abstract":"<div><p>Rising research and development costs, currently exceeding $3.5 billion per novel drug, reflect a five-decade decline in pharmaceutical R&amp;D efficiency. While recent reports suggest a potential turnaround, this review offers a systems-level analysis to explore whether this marks a structural shift or transient reversal. We analyzed financial data from the 200 largest pharmaceutical firms, novel drug approvals, and more than 80 000 clinical trials between 2012 and 2023. Our analysis revealed that despite recent stabilization, the pharmaceutical industry continues to face challenges, particularly due to elevated late-stage clinical attrition, suggesting that a sustained turnaround in R&amp;D efficiency remains elusive.</p></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104160"},"PeriodicalIF":6.5,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S135964462400285X/pdfft?md5=6183df0c7f5f5378cd212c69c2ae5b5f&pid=1-s2.0-S135964462400285X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142144531","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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
Neurotrophin peptidomimetics for the treatment of neurodegenerative diseases 用于治疗神经退行性疾病的神经营养素肽模拟物。
IF 6.5 2区 医学
Drug Discovery Today Pub Date : 2024-09-02 DOI: 10.1016/j.drudis.2024.104156
Dev Madhubala , Rosy Mahato , Mojibur R. Khan , Asis Bala , Ashis K. Mukherjee
{"title":"Neurotrophin peptidomimetics for the treatment of neurodegenerative diseases","authors":"Dev Madhubala ,&nbsp;Rosy Mahato ,&nbsp;Mojibur R. Khan ,&nbsp;Asis Bala ,&nbsp;Ashis K. Mukherjee","doi":"10.1016/j.drudis.2024.104156","DOIUrl":"10.1016/j.drudis.2024.104156","url":null,"abstract":"<div><p>Neurotrophins, such as nerve growth factor and brain-derived neurotrophic factor, play an essential role in the survival of neurons. However, incorporating better features can increase their therapeutic efficacy in neurodegenerative diseases (NDs). Peptidomimetics, which mimic these neurotrophins, show potential for treating NDs. This study emphasizes the use of peptidomimetics from neurotrophins for treating NDs and their benefits. By improving bioavailability and stability, these molecules can completely transform the therapy for NDs. This in-depth review guides researchers and pharmaceutical developers, providing insight into the changing field of neurodegenerative medicine.</p></div>","PeriodicalId":301,"journal":{"name":"Drug Discovery Today","volume":"29 11","pages":"Article 104156"},"PeriodicalIF":6.5,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142131450","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
首页 上一页 下一页 尾页
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
现在去查看 取消
×
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：481959085
Book学术官方微信