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Trends in pharmacological sciences最新文献

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VMAT structures reveal exciting targets for drug development. VMAT 结构揭示了令人兴奋的药物开发目标。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-05-01 Epub Date: 2024-02-29 DOI: 10.1016/j.tips.2024.02.004
Shimon Schuldiner, Lucy R Forrest
{"title":"VMAT structures reveal exciting targets for drug development.","authors":"Shimon Schuldiner, Lucy R Forrest","doi":"10.1016/j.tips.2024.02.004","DOIUrl":"10.1016/j.tips.2024.02.004","url":null,"abstract":"<p><p>Vesicular monoamine transporter (VMAT)-2 has a crucial role in the neurotransmission of biogenic amines. Recently, Dalton et al., Pidathala et al., Wu et al., and Wang et al. individually reported cryo-electron microscopy (EM) structures of human VMAT2, offering opportunities for developing improved therapeutics and deep insights into the functioning of this protein.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.9,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11191364/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140013272","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
Glymphatic-stagnated edema induced by traumatic brain injury. 创伤性脑损伤引发的脑水肿。
IF 13.8 1区 医学
Trends in pharmacological sciences Pub Date : 2024-05-01 Epub Date: 2024-01-29 DOI: 10.1016/j.tips.2024.01.005
Per Kristian Eide, Geir Ringstad
{"title":"Glymphatic-stagnated edema induced by traumatic brain injury.","authors":"Per Kristian Eide, Geir Ringstad","doi":"10.1016/j.tips.2024.01.005","DOIUrl":"10.1016/j.tips.2024.01.005","url":null,"abstract":"<p><p>Traumatic brain injury (TBI) outcomes are notably affected by brain edema. A recent report by Hussain et al. unveils a unique form, glymphatic-stagnated brain edema, that stems from impaired glymphatic and lymphatic drainage induced by noradrenergic activation. Consequently, pan-noradrenergic inhibition may emerge as an innovative treatment for TBI-related edema, challenging traditional therapeutic approaches.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139643005","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
Directions to overcome therapy resistance in cancer. 克服癌症抗药性的方向
IF 13.8 1区 医学
Trends in pharmacological sciences Pub Date : 2024-05-01 DOI: 10.1016/j.tips.2024.05.001
Ruth Nussinov, Thomas Weichhart, Zodwa Dlamini, Don L. Gibbons, Isabelle Van Seuningen, Jessica Konen, Huai-qiang Ju
{"title":"Directions to overcome therapy resistance in cancer.","authors":"Ruth Nussinov, Thomas Weichhart, Zodwa Dlamini, Don L. Gibbons, Isabelle Van Seuningen, Jessica Konen, Huai-qiang Ju","doi":"10.1016/j.tips.2024.05.001","DOIUrl":"https://doi.org/10.1016/j.tips.2024.05.001","url":null,"abstract":"","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141041578","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
Malolactone strikes: K-Ras-G12D's Achilles' heel Malolactone 罢工：K-Ras-G12D 的致命弱点
IF 13.8 1区 医学
Trends in pharmacological sciences Pub Date : 2024-04-22 DOI: 10.1016/j.tips.2024.04.001
Christos Adamopoulos, Kostas A. Papavassiliou, Athanasios G. Papavassiliou
{"title":"Malolactone strikes: K-Ras-G12D's Achilles' heel","authors":"Christos Adamopoulos, Kostas A. Papavassiliou, Athanasios G. Papavassiliou","doi":"10.1016/j.tips.2024.04.001","DOIUrl":"https://doi.org/10.1016/j.tips.2024.04.001","url":null,"abstract":"<p>In a recent study in <em>Nature Chemical Biology</em>, <span>Zheng <em>et al.</em></span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"8px\" viewbox=\"0 0 8 8\" width=\"8px\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg> exploiting strain release by malolactone-based electrophiles and designed a first-in-class covalent inhibitor that targets the elusive aspartate of the Kirsten rat sarcoma viral oncogene homolog (K-Ras)-G12D variant, which is highly prevalent in pancreatic cancer. The compound drastically inhibited oncogenic signaling and tumor growth in preclinical K-Ras-G12D-mutant pancreatic cancer models, expanding treatment potential beyond K-Ras-G12C-targeted therapies.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140634852","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
AML treatment: conventional chemotherapy and emerging novel agents 急性髓细胞性白血病治疗：传统化疗和新型药物
IF 13.8 1区 医学
Trends in pharmacological sciences Pub Date : 2024-04-20 DOI: 10.1016/j.tips.2024.03.005
Mark Forsberg, Marina Konopleva
{"title":"AML treatment: conventional chemotherapy and emerging novel agents","authors":"Mark Forsberg, Marina Konopleva","doi":"10.1016/j.tips.2024.03.005","DOIUrl":"https://doi.org/10.1016/j.tips.2024.03.005","url":null,"abstract":"<p>Acute myeloid leukemia (AML) is driven by complex mutations and cytogenetic abnormalities with profound tumoral heterogeneity, making it challenging to treat. Ten years ago, the 5-year survival rate of patients with AML was only 29% with conventional chemotherapy and stem cell transplantation. All attempts to improve conventional therapy over the previous 40 years had failed. Now, new genomic, immunological, and molecular insights have led to a renaissance in AML therapy. Improvements to standard chemotherapy and a wave of new targeted therapies have been developed. However, how best to incorporate these advances into frontline therapy and sequence them in relapse is not firmly established. In this review, we highlight current treatments of AML, targeted agents, and pioneering attempts to synthesize these developments into a rational standard of care (SoC).</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140624095","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
Electroceuticals: emerging applications beyond the nervous system and excitable tissues 电疗药物：神经系统和可兴奋组织之外的新兴应用
IF 13.8 1区 医学
Trends in pharmacological sciences Pub Date : 2024-04-18 DOI: 10.1016/j.tips.2024.03.001
Swarnalatha Balasubramanian, David A. Weston, Michael Levin, Devon Charles Cardoso Davidian
{"title":"Electroceuticals: emerging applications beyond the nervous system and excitable tissues","authors":"Swarnalatha Balasubramanian, David A. Weston, Michael Levin, Devon Charles Cardoso Davidian","doi":"10.1016/j.tips.2024.03.001","DOIUrl":"https://doi.org/10.1016/j.tips.2024.03.001","url":null,"abstract":"<p>Electroceuticals have evolved beyond devices manipulating neuronal signaling for symptomatic treatment, becoming more precise and disease modulating and expanding beyond the nervous system. These advancements promise transformative applications in arthritis, cancer treatment, tissue regeneration, and more. Here, we discuss these recent advances and offer insights for future research.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140624291","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
Heterobifunctional small molecules to modulate RNA function 调节 RNA 功能的异种功能小分子
IF 13.8 1区 医学
Trends in pharmacological sciences Pub Date : 2024-04-18 DOI: 10.1016/j.tips.2024.03.006
Sandra Kovachka, Yuquan Tong, Jessica L. Childs-Disney, Matthew D. Disney
{"title":"Heterobifunctional small molecules to modulate RNA function","authors":"Sandra Kovachka, Yuquan Tong, Jessica L. Childs-Disney, Matthew D. Disney","doi":"10.1016/j.tips.2024.03.006","DOIUrl":"https://doi.org/10.1016/j.tips.2024.03.006","url":null,"abstract":"<p>RNA has diverse cellular functionality, including regulating gene expression, protein translation, and cellular response to stimuli, due to its intricate structures. Over the past decade, small molecules have been discovered that target functional structures within cellular RNAs and modulate their function. Simple binding, however, is often insufficient, resulting in low or even no biological activity. To overcome this challenge, heterobifunctional compounds have been developed that can covalently bind to the RNA target, alter RNA sequence, or induce its cleavage. Herein, we review the recent progress in the field of RNA-targeted heterobifunctional compounds using representative case studies. We identify critical gaps and limitations and propose a strategic pathway for future developments of RNA-targeted molecules with augmented functionalities.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140634862","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
Direct in vivo CAR T cell engineering 直接体内 CAR T 细胞工程
IF 13.8 1区 医学
Trends in pharmacological sciences Pub Date : 2024-04-12 DOI: 10.1016/j.tips.2024.03.004
Lauralie Short, Robert A. Holt, Pieter R. Cullis, Laura Evgin
{"title":"Direct in vivo CAR T cell engineering","authors":"Lauralie Short, Robert A. Holt, Pieter R. Cullis, Laura Evgin","doi":"10.1016/j.tips.2024.03.004","DOIUrl":"https://doi.org/10.1016/j.tips.2024.03.004","url":null,"abstract":"<p>T cells modified to express intelligently designed chimeric antigen receptors (CARs) are exceptionally powerful therapeutic agents for relapsed and refractory blood cancers and have the potential to revolutionize therapy for many other diseases. To circumvent the complexity and cost associated with broad-scale implementation of <em>ex vivo</em> manufactured adoptive cell therapy products, alternative strategies to generate CAR T cells <em>in vivo</em> by direct infusion of nanoparticle-formulated nucleic acids or engineered viral vectors under development have received a great deal of attention in the past few years. Here, we outline the <em>ex vivo</em> manufacturing process as a motivating framework for direct <em>in vivo</em> strategies and discuss emerging data from preclinical models to highlight the potency of the <em>in vivo</em> approach, the applicability for new disease indications, and the remaining challenges associated with clinical readiness, including delivery specificity, long term efficacy, and safety.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140624290","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
Frizzleds act as dynamic pharmacological entities Frizzleds 作为动态药理学实体发挥作用
IF 13.8 1区 医学
Trends in pharmacological sciences Pub Date : 2024-04-08 DOI: 10.1016/j.tips.2024.03.003
{"title":"Frizzleds act as dynamic pharmacological entities","authors":"","doi":"10.1016/j.tips.2024.03.003","DOIUrl":"https://doi.org/10.1016/j.tips.2024.03.003","url":null,"abstract":"Abstract not available","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140624286","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 methionine metabolism in cancer: opportunities and challenges 以癌症中的蛋氨酸代谢为靶点：机遇与挑战
IF 13.8 1区 医学
Trends in pharmacological sciences Pub Date : 2024-04-05 DOI: 10.1016/j.tips.2024.03.002
Peng Bin, Chuanlong Wang, Hangchao Zhang, Yuqi Yan, Wenkai Ren
{"title":"Targeting methionine metabolism in cancer: opportunities and challenges","authors":"Peng Bin, Chuanlong Wang, Hangchao Zhang, Yuqi Yan, Wenkai Ren","doi":"10.1016/j.tips.2024.03.002","DOIUrl":"https://doi.org/10.1016/j.tips.2024.03.002","url":null,"abstract":"<p>Reprogramming of methionine metabolism is a conserved hallmark of tumorigenesis. Recent studies have revealed mechanisms regulating methionine metabolism within the tumor microenvironment (TME) that drive both cancer development and antitumor immunity evasion. In this review article we summarize advancements in our understanding of tumor regulation of methionine metabolism and therapies in development that target tumor methionine metabolism. We also delineate the challenges of methionine blockade therapies in cancer and discuss emerging strategies to address them.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":null,"pages":null},"PeriodicalIF":13.8,"publicationDate":"2024-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140624316","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
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