发布求助
文献互助 智能选刊 最新文献

Trends in pharmacological sciences最新文献

筛选
英文 中文
KRASG12C/mTORC1 inhibition: a powerful duo in NSCLC therapeutics. KRASG12C/mTORC1抑制：非小细胞肺癌治疗中的一个强大的组合。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-05-01 Epub Date: 2025-04-14 DOI: 10.1016/j.tips.2025.03.009
Antonios N Gargalionis, Kostas A Papavassiliou, Athanasios G Papavassiliou
{"title":"KRAS<sup>G12C</sup>/mTORC1 inhibition: a powerful duo in NSCLC therapeutics.","authors":"Antonios N Gargalionis, Kostas A Papavassiliou, Athanasios G Papavassiliou","doi":"10.1016/j.tips.2025.03.009","DOIUrl":"https://doi.org/10.1016/j.tips.2025.03.009","url":null,"abstract":"<p><p>In a recent report in Nature Communications, Kitai et al. designed a combinational treatment based on targeting the active-state KRAS<sup>G12C</sup>-mutant variant that characterizes a substantial subset of non-small-cell lung cancer (NSCLC) cases. The authors highlighted that dual targeting with KRAS<sup>G12C</sup> (ON) and mammalian target of rapamycin (mTOR) complex (mTORC)-1-selective inhibition potentially provides a new strategy to overcome drug resistance.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":"46 5","pages":"389-391"},"PeriodicalIF":13.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144014993","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
CRISPR/Cas technologies for cancer drug discovery and treatment. CRISPR/Cas技术用于癌症药物的发现和治疗。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-05-01 Epub Date: 2025-03-24 DOI: 10.1016/j.tips.2025.02.009
Kevin C Wang, Tiffany Zheng, Basil P Hubbard
{"title":"CRISPR/Cas technologies for cancer drug discovery and treatment.","authors":"Kevin C Wang, Tiffany Zheng, Basil P Hubbard","doi":"10.1016/j.tips.2025.02.009","DOIUrl":"10.1016/j.tips.2025.02.009","url":null,"abstract":"<p><p>Clustered regularly interspaced short palindromic repeats (CRISPR) tools are revolutionizing the establishment of genotype-phenotype relationships and are transforming cell- and gene-based therapies. In the field of oncology, CRISPR/CRISPR-associated protein 9 (Cas9), Cas12, and Cas13 have advanced the generation of cancer models, the study of tumor evolution, the identification of target genes involved in cancer growth, and the discovery of genes involved in chemosensitivity and resistance. Moreover, preclinical therapeutic strategies employing CRISPR/Cas have emerged. These include the generation of chimeric antigen receptor T (CAR-T) cells and engineered immune cells, and the use of precision anticancer gene-editing agents to inactivate driver oncogenes, suppress tumor support genes, and cull cancer cells in response to genetic circuit output. This review summarizes the collective impact that CRISPR technology has had on basic and applied cancer research, and highlights the promises and challenges facing its clinical translation.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"437-452"},"PeriodicalIF":13.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711371","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
Venom peptides regulating Ca2+ homeostasis: neuroprotective potential. 调节Ca2+稳态的蛇毒肽：神经保护潜能。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-05-01 Epub Date: 2025-04-15 DOI: 10.1016/j.tips.2025.03.007
Jessica A I Muller, Lachlan A Bourke, Sam I D Campbell, Fernanda C Cardoso
{"title":"Venom peptides regulating Ca<sup>2+</sup> homeostasis: neuroprotective potential.","authors":"Jessica A I Muller, Lachlan A Bourke, Sam I D Campbell, Fernanda C Cardoso","doi":"10.1016/j.tips.2025.03.007","DOIUrl":"https://doi.org/10.1016/j.tips.2025.03.007","url":null,"abstract":"<p><p>Venom peptides specialized in modulating intracellular calcium ([Ca<sup>2+</sup>]<sub>i</sub>) offer a treasure trove of pharmacological properties to regulate aberrant Ca<sup>2+</sup> homeostasis in disease. Combined with emerging advances across peptide optimization, disease models, and functional bioassays, these venom peptides could unlock new therapies restoring Ca<sup>2+</sup> homeostasis. In this opinion, we explore the pharmacology of venom peptides modulating [Ca<sup>2+</sup>]<sub>i</sub> signaling along with recent breakthroughs propelling venom peptide-based drug discovery. We predict a transformative era in therapeutic development harnessing venom peptides targeting dysfunctional Ca<sup>2+</sup> signaling in intractable conditions such as neurodegenerative diseases.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":"46 5","pages":"407-421"},"PeriodicalIF":13.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144033844","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
Repurposing trifluoperazine for glioblastoma treatment. 三氟拉嗪在胶质母细胞瘤治疗中的应用
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-05-01 Epub Date: 2025-04-28 DOI: 10.1016/j.tips.2025.03.005
Manam Inushi De Silva, Hui K Gan, Cedric Bardy
{"title":"Repurposing trifluoperazine for glioblastoma treatment.","authors":"Manam Inushi De Silva, Hui K Gan, Cedric Bardy","doi":"10.1016/j.tips.2025.03.005","DOIUrl":"https://doi.org/10.1016/j.tips.2025.03.005","url":null,"abstract":"<p><p>Glioblastoma (GBM) remains a therapeutic challenge due to its heterogeneity and plasticity, which drive treatment resistance, especially when compounded by interactions with the brain microenvironment. Recent preclinical evidence indicates that trifluoperazine (TFP) inhibits treatment-induced malignant reprogramming of tumour cells, potentially helping to reduce tumour plasticity. TFP targets calmodulin, dopamine receptors, and stress-responsive proteins (nuclear protein 1, NUPR1). Through these mechanisms, TFP has been shown to reduce tumour growth, sensitise tumours to chemoradiotherapy, and prolong survival in xenograft animal models. The clinical safety profile of TFP is well known from its use as an antipsychotic, and recent preclinical evidence further indicates that TFP has low toxicity to healthy neurons and glia despite transient functional effects on dopamine receptors. This Opinion explores TFP mechanisms of action and clinical activity to assess its suitability as a repurposed therapeutic option for GBM.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":"46 5","pages":"392-406"},"PeriodicalIF":13.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000876","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
Suzetrigine for moderate to severe acute pain. 舒三嗪用于中度至重度急性疼痛。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-05-01 Epub Date: 2025-03-24 DOI: 10.1016/j.tips.2025.02.008
Eun Bee Cho, Chenyao Jiang, Zihan Wang, Ying Yu, Jianxiong Jiang
{"title":"Suzetrigine for moderate to severe acute pain.","authors":"Eun Bee Cho, Chenyao Jiang, Zihan Wang, Ying Yu, Jianxiong Jiang","doi":"10.1016/j.tips.2025.02.008","DOIUrl":"10.1016/j.tips.2025.02.008","url":null,"abstract":"","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"480-481"},"PeriodicalIF":13.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12049257/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711376","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
Structural pharmacology and mechanisms of GLP-1R signaling. GLP-1R信号传导的结构药理学和机制。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-05-01 Epub Date: 2025-04-11 DOI: 10.1016/j.tips.2025.03.003
Qingtong Zhou, Fenghui Zhao, Yao Zhang, Dehua Yang, Ming-Wei Wang
{"title":"Structural pharmacology and mechanisms of GLP-1R signaling.","authors":"Qingtong Zhou, Fenghui Zhao, Yao Zhang, Dehua Yang, Ming-Wei Wang","doi":"10.1016/j.tips.2025.03.003","DOIUrl":"https://doi.org/10.1016/j.tips.2025.03.003","url":null,"abstract":"<p><p>Glucagon-like peptide-1 receptor (GLP-1R), a class B1 G protein-coupled receptor, plays critical roles in glucose homeostasis. Recent structural pharmacology studies using cryogenic electron microscopy, X-ray crystallography, mass spectrometry, and functional analyses, have provided valuable insights into its activation by endogenous hormones and mono- or dual agonists like semaglutide and tirzepatide, highly effective in treating type 2 diabetes and obesity. They highlight significant conformational changes in the extracellular and transmembrane domains of GLP-1R that drive receptor activation and downstream signal transduction. Additionally, allosteric modulators, supported by emerging structural information, show great promises as an alternative strategy. Future research investigating unexplored effector interactions, biased signaling, weight rebound mechanisms, and personalized therapy strategies will be critical for developing better therapeutic agents targeting GLP-1R.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":"46 5","pages":"422-436"},"PeriodicalIF":13.9,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144036011","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 AMPK as a potential treatment for hepatic fibrosis in MASLD. 靶向AMPK作为MASLD肝纤维化的潜在治疗方法。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-04-28 DOI: 10.1016/j.tips.2025.03.008
Xavier Palomer, Jue-Rui Wang, Claudia Escalona, Siyuan Wu, Walter Wahli, Manuel Vázquez-Carrera
{"title":"Targeting AMPK as a potential treatment for hepatic fibrosis in MASLD.","authors":"Xavier Palomer, Jue-Rui Wang, Claudia Escalona, Siyuan Wu, Walter Wahli, Manuel Vázquez-Carrera","doi":"10.1016/j.tips.2025.03.008","DOIUrl":"https://doi.org/10.1016/j.tips.2025.03.008","url":null,"abstract":"<p><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease, and often progresses to hepatic fibrosis, cirrhosis, and liver failure. Despite its increasing prevalence, effective pharmacological treatments for MASLD-related fibrosis remain limited. Recent research has highlighted AMP-activated protein kinase (AMPK) as a key regulator of the processes that promote fibrogenesis, and AMPK activation shows potential in mitigating fibrosis. Advances in AMPK activators and deeper insights into their role in fibrotic pathways have recently revitalized interest in targeting AMPK for fibrosis treatment. This review discusses the molecular mechanisms linking AMPK to hepatic fibrosis and evaluates emerging AMPK-directed therapies. Furthermore, it addresses challenges in clinical translation. Importantly, we combine the latest mechanistic discoveries with recent therapeutic developments to provide a comprehensive perspective on AMPK as a target for hepatic fibrosis treatment.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":13.9,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144049837","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
HSV-1 as a gene delivery platform for cancer gene therapy. HSV-1作为癌症基因治疗的基因传递平台。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-04-01 Epub Date: 2025-03-10 DOI: 10.1016/j.tips.2025.02.006
Yangkun Shen, Hucheng Zhang, Mengzhou Xue, Chunfu Zheng, Qi Chen
{"title":"HSV-1 as a gene delivery platform for cancer gene therapy.","authors":"Yangkun Shen, Hucheng Zhang, Mengzhou Xue, Chunfu Zheng, Qi Chen","doi":"10.1016/j.tips.2025.02.006","DOIUrl":"10.1016/j.tips.2025.02.006","url":null,"abstract":"<p><p>Herpes simplex virus type 1 (HSV-1) is a DNA virus with strong replication capabilities, a large genomic payload (≥30 kb), and low toxicity, making it a prominent vector in cancer gene therapy. Clinically approved oncolytic HSV-1 (oHSV-1) variants, such as T-VEC and G47Δ, demonstrate safety and efficacy in localized tumors, but face challenges in treating metastatic disease. To address this issue, next-generation oHSV-1 designs focus on precision targeting and immune remodeling through the delivery of multiple exogenous genes. In this review, we provide an overview of the inherent characteristics of oHSV-1 as a gene delivery platform, focusing on its genetic modification strategies, safety challenges in clinical applications, and future directions to maximize its therapeutic potential.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"324-336"},"PeriodicalIF":13.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606437","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
Ribosome-directed cancer therapies: the tip of the iceberg? 核糖体导向的癌症治疗：冰山一角？
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-04-01 Epub Date: 2025-03-04 DOI: 10.1016/j.tips.2025.02.001
Gregory C Howard, William P Tansey
{"title":"Ribosome-directed cancer therapies: the tip of the iceberg?","authors":"Gregory C Howard, William P Tansey","doi":"10.1016/j.tips.2025.02.001","DOIUrl":"10.1016/j.tips.2025.02.001","url":null,"abstract":"<p><p>Ribosomes and ribosome biogenesis (RiBi) are universally corrupted in cancer, fueling the high rates of translation that sustain malignancy and creating opportunities for discriminating therapeutic intervention. Despite longstanding recognition of the promise of ribosome-directed cancer therapies, only a handful of such agents have been used in the clinic, and with limited success, and the true potential of this approach is unknown. In the past few years, however, understanding of cancer ribosome specialization and the intricacies of RiBi have advanced dramatically, opening opportunities that could not be imagined when existing agents were discovered. Here, we discuss the rationale for targeting ribosomes to treat cancer, review the limitations of current agents, and highlight an important set of recent discoveries we propose could be exploited to discover molecularly-targeted ribosome-directed cancer therapeutics.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"303-310"},"PeriodicalIF":13.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568200","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
Pain Signaling by GPCRs and RTKs. gpcr和rtk的疼痛信号传导。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2025-04-01 Epub Date: 2025-03-08 DOI: 10.1016/j.tips.2025.02.002
Brain L Schmidt, Francesco De Logu, Romina Nassini, Pierangelo Geppetti, Nigel W Bunnett
{"title":"Pain Signaling by GPCRs and RTKs.","authors":"Brain L Schmidt, Francesco De Logu, Romina Nassini, Pierangelo Geppetti, Nigel W Bunnett","doi":"10.1016/j.tips.2025.02.002","DOIUrl":"10.1016/j.tips.2025.02.002","url":null,"abstract":"<p><p>Chronic pain is common and debilitating, yet is inadequately treated by current therapies, which can have life-threatening side effects. Treatments targeting G protein-coupled receptors (GPCRs) and receptor tyrosine kinases (RTKs), key pain mediators, often fail in clinical trials for unknown reasons. Here, we discuss the recent evidence that GPCRs and RTKs generate sustained signals from multiprotein signaling complexes or signalosomes in intracellular compartments to control chronic pain. We evaluate the evidence that selective antagonism of these intracellular signals provides more efficacious and long-lasting pain relief than antagonism of receptors at the surface of cells. We highlight how the identification of coreceptors and molecular scaffolds that underpin pain signaling by multiple receptors has identified new therapeutic targets for chronic pain, surmounting the redundancy of the pain signaling pathway.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"372-385"},"PeriodicalIF":13.9,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11972155/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143587228","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
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