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Trends in pharmacological sciences最新文献

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MICUs protect the heart by regulating mitochondrial calcium. MICU 通过调节线粒体钙质来保护心脏。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-11-01 Epub Date: 2024-10-14 DOI: 10.1016/j.tips.2024.09.010
Ulas Ozkurede, Shanmugasundaram Pakkiriswami, Julia C Liu
{"title":"MICUs protect the heart by regulating mitochondrial calcium.","authors":"Ulas Ozkurede, Shanmugasundaram Pakkiriswami, Julia C Liu","doi":"10.1016/j.tips.2024.09.010","DOIUrl":"10.1016/j.tips.2024.09.010","url":null,"abstract":"<p><p>Regulation of mitochondrial calcium uptake by the mitochondrial calcium uniporter (mtCU) complex is crucial for heart function. In a recent study, Hasan et al. demonstrated that mitochondrial calcium uptake (MICU)1 and MICU2, regulatory subunits of the complex, help maintain calcium homeostasis in cardiac mitochondria, providing potential targets for therapies aimed at improving mitochondrial function in heart disease.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"950-952"},"PeriodicalIF":13.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11637328/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475600","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
Phenotypic approaches for CNS drugs. 中枢神经系统药物的表型方法。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-11-01 Epub Date: 2024-10-21 DOI: 10.1016/j.tips.2024.09.003
Raahul Sharma, Caitlin R M Oyagawa, Hamid Abbasi, Michael Dragunow, Daniel Conole
{"title":"Phenotypic approaches for CNS drugs.","authors":"Raahul Sharma, Caitlin R M Oyagawa, Hamid Abbasi, Michael Dragunow, Daniel Conole","doi":"10.1016/j.tips.2024.09.003","DOIUrl":"10.1016/j.tips.2024.09.003","url":null,"abstract":"<p><p>Central nervous system (CNS) drug development is plagued by high clinical failure rate. Phenotypic assays promote clinical translation of drugs by reducing complex brain diseases to measurable, clinically valid phenotypes. We critique recent platforms integrating patient-derived brain cells, which most accurately recapitulate CNS disease phenotypes, with higher throughput models, including immortalized cells, to balance validity and scalability. These platforms were screened with conventional commercial chemogenomic compound libraries. We explore emerging library curation strategies to improve hit rate and quality, and screening novel fragment libraries as alternatives, for more tractable drug target deconvolution. The clinically relevant models used in these platforms could harbor important, unidentified drug targets, so we review evolving agnostic target deconvolution approaches, including chemical proteomics and artificial intelligence (AI), which aid in phenotypic screening hit mechanism elucidation, thereby facilitating rational hit-to-drug optimization.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"997-1017"},"PeriodicalIF":13.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142508709","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
Novel antagonists reveal the mechanism of PXR inhibition. 新型拮抗剂揭示了 PXR 的抑制机制。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-11-01 Epub Date: 2024-10-16 DOI: 10.1016/j.tips.2024.10.002
Rajamanikkam Kamaraj, Petr Pavek
{"title":"Novel antagonists reveal the mechanism of PXR inhibition.","authors":"Rajamanikkam Kamaraj, Petr Pavek","doi":"10.1016/j.tips.2024.10.002","DOIUrl":"10.1016/j.tips.2024.10.002","url":null,"abstract":"<p><p>The pregnane X receptor (PXR) is a key regulator of metabolism, but the mechanisms underlying its antagonism remain unclear. Garcia-Maldonado et al. reported potent new antagonists and their co-crystal structures, revealing molecular determinants of PXR antagonism and paving the way for developing antagonists as therapeutics and preventing undesirable PXR activation.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"961-963"},"PeriodicalIF":13.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142475602","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
Advancing cancer research. 推进癌症研究。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-11-01 Epub Date: 2024-10-30 DOI: 10.1016/j.tips.2024.10.004
Cornelius Y Taabazuing, Whitney S Henry, Michael U J Oliphant, Shamara S Lawrence
{"title":"Advancing cancer research.","authors":"Cornelius Y Taabazuing, Whitney S Henry, Michael U J Oliphant, Shamara S Lawrence","doi":"10.1016/j.tips.2024.10.004","DOIUrl":"10.1016/j.tips.2024.10.004","url":null,"abstract":"","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"943-949"},"PeriodicalIF":13.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142547653","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
DOT1L: orchestrating methylation-dependent radiotheRAPy responses via BRCA1. DOT1L：通过 BRCA1 协调甲基化依赖性放射反应。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-11-01 Epub Date: 2024-10-09 DOI: 10.1016/j.tips.2024.09.008
Justin W Leung, Kyle M Miller
{"title":"DOT1L: orchestrating methylation-dependent radiotheRAPy responses via BRCA1.","authors":"Justin W Leung, Kyle M Miller","doi":"10.1016/j.tips.2024.09.008","DOIUrl":"10.1016/j.tips.2024.09.008","url":null,"abstract":"<p><p>Breast Cancer Type 1 Susceptibility Protein (BRCA)-1 existing in several functionally distinct complexes, promotes DNA repair of DNA double-strand breaks (DSBs). A recent study by Tang and colleagues identifies the lysine methyltransferase Disruptor of Telomeric Silencing 1-Like (DOT1L) involved in modifying Receptor-Associated Protein 80 (RAP80) to promote BRCA1-A complex localization and repair functions at DNA breaks. This study illuminates a potential therapeutic target for cancer radiotherapy.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"955-957"},"PeriodicalIF":13.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580024/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142401423","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
Targeting white adipose tissue to combat insulin resistance. 以白色脂肪组织为目标，对抗胰岛素抵抗。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-10-01 Epub Date: 2024-07-24 DOI: 10.1016/j.tips.2024.06.008
Yiheng Huang, Pingyi Gao, Lawrence H Young, Dake Qi
{"title":"Targeting white adipose tissue to combat insulin resistance.","authors":"Yiheng Huang, Pingyi Gao, Lawrence H Young, Dake Qi","doi":"10.1016/j.tips.2024.06.008","DOIUrl":"10.1016/j.tips.2024.06.008","url":null,"abstract":"<p><p>Metabolic and endocrine dysfunction of white adipose tissue (WAT) is linked to inflammation, which has been considered a key mechanism of insulin resistance (IR). However, recent studies revealed non-inflammatory mechanisms of IR in WAT, which may trigger inflammation and could be developed as a novel strategy to counteract IR.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"868-871"},"PeriodicalIF":13.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141761115","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
New insights into SYK targeting in solid tumors. 实体瘤中 SYK 靶向治疗的新见解。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-10-01 Epub Date: 2024-09-24 DOI: 10.1016/j.tips.2024.08.006
Shweta Joshi
{"title":"New insights into SYK targeting in solid tumors.","authors":"Shweta Joshi","doi":"10.1016/j.tips.2024.08.006","DOIUrl":"10.1016/j.tips.2024.08.006","url":null,"abstract":"<p><p>Spleen tyrosine kinase (SYK) is predominantly expressed in hematopoietic cells and has been extensively studied for its pivotal role in B cell malignancies and autoimmune diseases. In epithelial solid tumors, SYK shows a paradoxical role, acting as a tumor suppressor in some cancers while driving tumor growth in others. Recent preclinical studies have identified the role of SYK in the tumor microenvironment (TME), revealing that SYK signaling in immune cells, especially B cells, and myeloid cells, promote immunosuppression, tumor growth, and metastasis across various solid tumors. This review explores the emerging roles of SYK in solid tumors, the mechanisms of SYK activation, and findings from preclinical and clinical studies of SYK inhibitors as either standalone treatments or in combination with immunotherapy or chemotherapy for solid tumors.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"904-918"},"PeriodicalIF":13.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11984332/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354509","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
How can quantum computing be applied in clinical trial design and optimization? 如何将量子计算应用于临床试验设计和优化？
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-10-01 Epub Date: 2024-09-23 DOI: 10.1016/j.tips.2024.08.005
Hakan Doga, Aritra Bose, M Emre Sahin, Joao Bettencourt-Silva, Anh Pham, Eunyoung Kim, Alan Andress, Sudhir Saxena, Laxmi Parida, Jan Lukas Robertus, Hideaki Kawaguchi, Radwa Soliman, Daniel Blankenberg
{"title":"How can quantum computing be applied in clinical trial design and optimization?","authors":"Hakan Doga, Aritra Bose, M Emre Sahin, Joao Bettencourt-Silva, Anh Pham, Eunyoung Kim, Alan Andress, Sudhir Saxena, Laxmi Parida, Jan Lukas Robertus, Hideaki Kawaguchi, Radwa Soliman, Daniel Blankenberg","doi":"10.1016/j.tips.2024.08.005","DOIUrl":"10.1016/j.tips.2024.08.005","url":null,"abstract":"<p><p>Clinical trials are necessary for assessing the safety and efficacy of treatments. However, trial timelines are severely delayed with minimal success due to a multitude of factors, including imperfect trial site selection, cohort recruitment challenges, lack of efficacy, absence of reliable biomarkers, etc. Each of these factors possesses a unique computational challenge, such as data management, trial simulations, statistical analyses, and trial optimization. Recent advancements in quantum computing offer a promising opportunity to overcome these hurdles. In this opinion we uniquely explore the application of quantum optimization and quantum machine learning (QML) to the design and execution of clinical trials. We examine the current capabilities and limitations of quantum computing and outline its potential to streamline clinical trials.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"880-891"},"PeriodicalIF":13.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354508","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
Neurofilament light chain as a biomarker of chemotherapy-induced peripheral neuropathy. 作为化疗诱发周围神经病变生物标志物的神经丝蛋白轻链
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-10-01 Epub Date: 2024-09-05 DOI: 10.1016/j.tips.2024.08.001
Nanna E Andersen, Wolfgang Boehmerle, Petra Huehnchen, Tore B Stage
{"title":"Neurofilament light chain as a biomarker of chemotherapy-induced peripheral neuropathy.","authors":"Nanna E Andersen, Wolfgang Boehmerle, Petra Huehnchen, Tore B Stage","doi":"10.1016/j.tips.2024.08.001","DOIUrl":"10.1016/j.tips.2024.08.001","url":null,"abstract":"<p><p>Chemotherapy-induced peripheral neuropathy (CIPN) is a common side effect of chemotherapy. The frequency of CIPN ranges from one in three to almost all patients depending on type of chemotherapy and dose. It causes symptoms that can range from sensitivity to touch and numbness to neuropathic pain in hands and feet. CIPN is notoriously difficult to grade objectively and has mostly relied on a clinician- or patient-based rating that is subjective and poorly reproducible. Thus, considerable effort has been aimed at identifying objective biomarkers of CIPN. Recent in vitro, animal, and clinical studies suggest that neurofilament light chain (NFL), a structural neuronal protein, may be an objective biomarker of CIPN. NFL released from cells to cell culture media reflects in vitro neurotoxicity, while NFL in serum reflects neuronal damage caused by chemotherapy in rodent models. Finally, NFL in serum may be a diagnostic biomarker of CIPN, but its prognostic ability to predict CIPN requires prospective evaluation. We discuss current limitations and future perspectives on the use of NFL as a preclinical and clinical biomarker of CIPN.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"872-879"},"PeriodicalIF":13.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146303","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 TRPM channels for cerebral ischemia-reperfusion injury. 针对脑缺血再灌注损伤的 TRPM 通道。
IF 13.9 1区 医学
Trends in pharmacological sciences Pub Date : 2024-10-01 Epub Date: 2024-07-16 DOI: 10.1016/j.tips.2024.06.005
Dai-Qiang Liu, Wei Mei, Ya-Qun Zhou, Hong Xi
{"title":"Targeting TRPM channels for cerebral ischemia-reperfusion injury.","authors":"Dai-Qiang Liu, Wei Mei, Ya-Qun Zhou, Hong Xi","doi":"10.1016/j.tips.2024.06.005","DOIUrl":"10.1016/j.tips.2024.06.005","url":null,"abstract":"<p><p>Transient receptor potential melastatin (TRPM) channels have emerged as potential therapeutic targets for cerebral ischemia-reperfusion (I/R) injury. We highlight recent findings on the involvement of TRPM channels in oxidative stress, mitochondrial dysfunction, inflammation, and calcium overload. We also discuss the challenges and future directions in targeting TRPM channels for cerebral I/R injury.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"862-867"},"PeriodicalIF":13.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141634629","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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