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'Living drugs' target CD70 in advanced renal tumors. 针对晚期肾肿瘤CD70的 "活药物
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-09-01 Epub Date: 2024-07-29 DOI: 10.1016/j.tips.2024.07.002
Kilian Wagner, Peter J Siska
{"title":"'Living drugs' target CD70 in advanced renal tumors.","authors":"Kilian Wagner, Peter J Siska","doi":"10.1016/j.tips.2024.07.002","DOIUrl":"10.1016/j.tips.2024.07.002","url":null,"abstract":"<p><p>Cellular therapies against solid tumors face three major barriers: low persistence, insufficient specificity, and high costs. In a recent study, Pal et al. tackle these challenges in kidney cancer by using novel, 'persistence-tuned' allogeneic chimeric antigen receptor (CAR) T cells directed against a stable antigen.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141856570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Targeting the STAT3 pathway with STAT3 degraders. 用 STAT3 降解剂靶向 STAT3 通路。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-09-01 Epub Date: 2024-08-07 DOI: 10.1016/j.tips.2024.07.003
Zhijie Wang, Xiaotong Liao, Haiqi He, Xia Guo, Jianjun Chen
{"title":"Targeting the STAT3 pathway with STAT3 degraders.","authors":"Zhijie Wang, Xiaotong Liao, Haiqi He, Xia Guo, Jianjun Chen","doi":"10.1016/j.tips.2024.07.003","DOIUrl":"10.1016/j.tips.2024.07.003","url":null,"abstract":"<p><p>Signal transducer and activator of transcription 3 (STAT3) has been widely considered as a therapeutic target for various diseases, especially tumors. Thus far, several STAT3 inhibitors have been advanced to clinical trials; however, the development of STAT3 inhibitors is hindered by numerous dilemmas. Fortunately, STAT3 degraders represent an alternative and promising strategy to block STAT3, attracting extensive research interest. Here, we analyze the recent advancements of STAT3 degraders, including proteolysis targeting chimeras (PROTACs) and small-molecule natural products, focusing on their structures, mechanisms, and biological activities. We discuss the potential opportunities and challenges for developing STAT3 degraders. It is hoped that this Review will provide insights into the discovery of potent STAT3-targeting drugs.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Role of hypoxia-inducible factor 1 in type 1 diabetes. 低氧诱导因子 1 在 1 型糖尿病中的作用。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-09-01 Epub Date: 2024-08-09 DOI: 10.1016/j.tips.2024.07.001
Raphael R Fagundes, Arnaud Zaldumbide, Cormac T Taylor
{"title":"Role of hypoxia-inducible factor 1 in type 1 diabetes.","authors":"Raphael R Fagundes, Arnaud Zaldumbide, Cormac T Taylor","doi":"10.1016/j.tips.2024.07.001","DOIUrl":"10.1016/j.tips.2024.07.001","url":null,"abstract":"<p><p>Type 1 diabetes (T1D) is a common autoimmune disease in which dysregulated glucose metabolism is a key feature. T1D is both poorly understood and in need of improved therapeutics. Hypoxia is frequently encountered in multiple tissues in T1D patients including the pancreas and sites of diabetic complications. Hypoxia-inducible factor (HIF)-1, a ubiquitous master regulator of the adaptive response to hypoxia, promotes glucose metabolism through transcriptional and non-transcriptional mechanisms and alters disease progression in multiple preclinical T1D models. However, how HIF-1 activation in β-cells of the pancreas and immune cells (two key cell types in T1D) ultimately affects disease progression remains controversial. We discuss recent advances in our understanding of the role of hypoxia/HIF-1-induced glycolysis in T1D and explore the possible use of drugs targeting this pathway as potential new therapeutics.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141914115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Epitope landscape in autoimmune neurological disease and beyond. 自身免疫性神经疾病及其他疾病的表位图谱。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-09-01 Epub Date: 2024-08-23 DOI: 10.1016/j.tips.2024.07.007
Ivan Talucci, Hans M Maric
{"title":"Epitope landscape in autoimmune neurological disease and beyond.","authors":"Ivan Talucci, Hans M Maric","doi":"10.1016/j.tips.2024.07.007","DOIUrl":"10.1016/j.tips.2024.07.007","url":null,"abstract":"<p><p>Autoantibody binding has a central role in autoimmune diseases and has also been linked to cancer, infections, and behavioral disorders. Autoimmune neurological diseases remain misclassified also due to an incomplete understanding of the underlying disease-specific epitopes. Such epitopes are crucial for both pathology and diagnosis, but have historically been overlooked. Recent technological advancements have enabled the exploration of these epitopes, potentially opening novel clinical avenues. The precise identification of novel B and T cell epitopes and their autoreactivity has led to the discovery of autoantigen-specific biomarkers for patients at high risk of autoimmune neurological diseases. In this review, we propose utilizing newly available synthetic and cellular-surface display technologies and guide epitope-focused studies to unlock the potential of disease-specific epitopes for improving diagnosis and treatments. Additionally, we offer recommendations to guide emerging epitope-focused studies to broaden the current landscape.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Nanotherapy for human papillomavirus-associated cancers: breakthroughs and challenges. 人类乳头瘤病毒相关癌症的纳米疗法：突破与挑战。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-09-01 Epub Date: 2024-08-24 DOI: 10.1016/j.tips.2024.07.004
Jéssica Lopes-Nunes, Paula A Oliveira, Carla Cruz
{"title":"Nanotherapy for human papillomavirus-associated cancers: breakthroughs and challenges.","authors":"Jéssica Lopes-Nunes, Paula A Oliveira, Carla Cruz","doi":"10.1016/j.tips.2024.07.004","DOIUrl":"10.1016/j.tips.2024.07.004","url":null,"abstract":"<p><p>Human papillomaviruses (HPVs) are well-known causative agents of several cancers, yet selective therapies remain under investigation. Nanoparticles, for instance, are emerging as promising solutions to enhance the delivery and efficacy of therapeutic approaches. Despite the increasing number of nanotherapies offering advantages over current treatments, only one has advanced to clinical trials. This review highlights recent advances in nanotherapies for HPV-associated cancers, focusing on the delivery of small molecules, gene-targeted therapies, and vaccines. Some of the challenges faced in nanotherapies translation for clinical application are discussed, emphasizing the most used preclinical models that fail to accurately predict human responses, thereby hindering proper evaluation of nanotherapies. Additionally, we explore and discuss alternative promising new preclinical models that could pave the way for more effective nanotherapeutic evaluations.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.9,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056600","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Subscription and Copyright Information 订阅和版权信息
IF 13.8 1区 医学
Trends in pharmacological sciences Pub Date : 2024-08-08 DOI: 10.1016/s0165-6147(24)00156-1
{"title":"Subscription and Copyright Information","authors":"","doi":"10.1016/s0165-6147(24)00156-1","DOIUrl":"https://doi.org/10.1016/s0165-6147(24)00156-1","url":null,"abstract":"No Abstract","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141946201","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Advisory Board and Contents 咨询委员会和内容
IF 13.8 1区 医学
Trends in pharmacological sciences Pub Date : 2024-08-08 DOI: 10.1016/s0165-6147(24)00152-4
{"title":"Advisory Board and Contents","authors":"","doi":"10.1016/s0165-6147(24)00152-4","DOIUrl":"https://doi.org/10.1016/s0165-6147(24)00152-4","url":null,"abstract":"No Abstract","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141946134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Magnesium for disease treatment and prevention: emerging mechanisms and opportunities. 镁用于疾病治疗和预防：新兴机制和机遇。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-08-01 Epub Date: 2024-07-16 DOI: 10.1016/j.tips.2024.06.004
Qi Gao, Onur Cil
{"title":"Magnesium for disease treatment and prevention: emerging mechanisms and opportunities.","authors":"Qi Gao, Onur Cil","doi":"10.1016/j.tips.2024.06.004","DOIUrl":"10.1016/j.tips.2024.06.004","url":null,"abstract":"<p><p>Magnesium (Mg<sup>2+</sup>) is a commonly used dietary supplement for the prevention and treatment of diseases. However, the efficacy and mechanisms of action of Mg<sup>2+</sup> in most diseases have been controversial because of conflicting findings in earlier studies. Recent clinical and preclinical studies provide novel insights into the use of Mg<sup>2+</sup> for the treatment and prevention of diseases affecting different organ systems. In this review, we provide an overview of recent clinical evidence for, and controversies over, the medical benefits of Mg<sup>2+</sup>. In addition, we critically discuss recent advances in understanding the mechanisms of action of Mg<sup>2+</sup>, which could enable the development of novel targeted therapies.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141634628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
Multiple hERG channel blocking pathways: implications for macromolecules. 多种 hERG 通道阻断途径：对大分子的影响。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-08-01 Epub Date: 2024-07-22 DOI: 10.1016/j.tips.2024.06.003
Bernd J Zünkler
{"title":"Multiple hERG channel blocking pathways: implications for macromolecules.","authors":"Bernd J Zünkler","doi":"10.1016/j.tips.2024.06.003","DOIUrl":"10.1016/j.tips.2024.06.003","url":null,"abstract":"<p><p>Numerous non-cardiovascular drugs have a potential to induce life-threatening torsades de pointes (TdP) ventricular cardiac arrhythmias by blocking human ether-à-go-go-related gene (hERG) currents via binding to the channel's inner cavity. Identification of the hERG current-inhibiting properties of candidate drugs is performed focusing on binding sites in the channel pore. It has been suggested that biologicals have a low likelihood of hERG current inhibition, since their poor diffusion across the plasma membrane prevents them from reaching the binding site in the channel pore. However, biologicals could influence hERG channel function by binding to 'unconventional' noncanonical binding sites. This Opinion gives an overview on noncanonical blockers of hERG channels that might be of relevance for the assessment of the possible torsadogenic potential of macromolecular therapeutics.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141752917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A novel function of the M2 muscarinic receptor. M2毒蕈碱受体的新功能
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-08-01 Epub Date: 2024-06-08 DOI: 10.1016/j.tips.2024.05.010
Jürgen Wess, Liu Liu
{"title":"A novel function of the M<sub>2</sub> muscarinic receptor.","authors":"Jürgen Wess, Liu Liu","doi":"10.1016/j.tips.2024.05.010","DOIUrl":"10.1016/j.tips.2024.05.010","url":null,"abstract":"<p><p>The M<sub>2</sub> muscarinic receptor (M2R) is a prototypic class A G protein-coupled receptor (GPCR). Interestingly, Fasciani et al. recently identified an internal translation start site within the M<sub>2</sub> receptor mRNA, directing the expression of a C-terminal receptor fragment. Elevated during cellular stress, this polypeptide localizes to mitochondria where it inhibits oxidative phosphorylation.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.9,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11316642/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141296744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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
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