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Trends in pharmacological sciences最新文献

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Centanafadine (Simtriyo): a triple monoamine reuptake inhibitor for ADHD. Centanafadine (Simtriyo)：一种用于ADHD的三重单胺再摄取抑制剂。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-10-01 Epub Date: 2026-09-12 DOI: 10.1016/j.tips.2026.08.011
Juqian Han, Chenyao Jiang, Alyssia Antwania Pruitt, Ying Yu, Jianxiong Jiang
{"title":"Centanafadine (Simtriyo): a triple monoamine reuptake inhibitor for ADHD.","authors":"Juqian Han, Chenyao Jiang, Alyssia Antwania Pruitt, Ying Yu, Jianxiong Jiang","doi":"10.1016/j.tips.2026.08.011","DOIUrl":"10.1016/j.tips.2026.08.011","url":null,"abstract":"","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"1186-1187"},"PeriodicalIF":24.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13591490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944721","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
Deubiquitinases in mitophagy: therapeutic control of mitochondrial quality. 线粒体自噬中的去泛素酶：线粒体质量的治疗控制。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-10-01 Epub Date: 2026-09-12 DOI: 10.1016/j.tips.2026.08.009
Yang Xu, Bahareh Behrouz, Andrew Lee, Gang Xin, Nuo Sun
{"title":"Deubiquitinases in mitophagy: therapeutic control of mitochondrial quality.","authors":"Yang Xu, Bahareh Behrouz, Andrew Lee, Gang Xin, Nuo Sun","doi":"10.1016/j.tips.2026.08.009","DOIUrl":"10.1016/j.tips.2026.08.009","url":null,"abstract":"<p><p>Mitochondrial quality control is essential for maintaining cellular and tissue homeostasis. Mitophagy, the selective autophagic removal of damaged mitochondria, is a central component of this process, and defects in mitophagy are increasingly linked to neurodegeneration, cardiovascular disease, cancer, and inherited mitochondrial disorders. Ubiquitin-dependent tagging of outer mitochondrial membrane proteins is a major mechanism for marking damaged mitochondria for clearance; however, recent advances reveal that mitochondrial deubiquitinases (DUBs) shape ubiquitin signaling at damaged mitochondria, thereby influencing the efficiency and selectivity of mitochondrial turnover. Moreover, DUBs are emerging as context-dependent editors of the mitochondrial ubiquitin code that link mitophagy to disease pathogenesis and therapeutic intervention. Here, we synthesize current understanding of mitochondrial DUBs in physiology and disease and discuss emerging pharmacological strategies to guide the development of mitophagy-targeted therapeutics.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"1099-1115"},"PeriodicalIF":24.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148944941","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
Heterochiral peptides reshaping class B1 GPCR agonism. 异手性肽重塑B1类GPCR激动作用。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-10-01 DOI: 10.1016/j.tips.2026.09.003
Heng Liu, Jianfeng Cai
{"title":"Heterochiral peptides reshaping class B1 GPCR agonism.","authors":"Heng Liu, Jianfeng Cai","doi":"10.1016/j.tips.2026.09.003","DOIUrl":"https://doi.org/10.1016/j.tips.2026.09.003","url":null,"abstract":"<p><p>A α-helical conformation within Class B1 G protein-coupled receptors agonists has been thought necessary for receptor activation. Gellman et al. suggested that selective replacement of L-amino acids with D-enantiomers could yield biased agonists. The new strategy helical would broaden the tools available for investigating agonist conformations and therapeutic potentials.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":24.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13632646/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149115356","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
Pyroptotic pores reopen the case for caspase inhibitors. 半胱天冬酶抑制剂的热腐孔重新打开。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-10-01 Epub Date: 2026-09-09 DOI: 10.1016/j.tips.2026.08.013
Ivano Amelio
{"title":"Pyroptotic pores reopen the case for caspase inhibitors.","authors":"Ivano Amelio","doi":"10.1016/j.tips.2026.08.013","DOIUrl":"10.1016/j.tips.2026.08.013","url":null,"abstract":"<p><p>Caspase inhibitors have repeatedly entered clinical trials but have not reached clinical practice due to toxicity and limited efficacy. Groborz and colleagues now show that gasdermin D pores admit otherwise membrane-impermeable inhibitors into pyroptotic cells, turning poor permeability into a mechanism of cell-state selectivity.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"1067-1068"},"PeriodicalIF":24.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148921071","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
Why pharmacological concepts survive despite scientific progress. 为什么药理学概念在科学进步的情况下仍然存在。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-10-01 Epub Date: 2026-09-05 DOI: 10.1016/j.tips.2026.08.008
Pierre-Louis Toutain, Peggy Gandia, Didier Concordet
{"title":"Why pharmacological concepts survive despite scientific progress.","authors":"Pierre-Louis Toutain, Peggy Gandia, Didier Concordet","doi":"10.1016/j.tips.2026.08.008","DOIUrl":"10.1016/j.tips.2026.08.008","url":null,"abstract":"<p><p>Scientific disciplines routinely reassess methods but rarely the concepts guiding scientific reasoning. We identify three mechanisms of conceptual persistence: amnesia, institutionalisation, and reification-the process by which an operational construct is regarded as biological reality. These mechanisms may impede scientific self-correction, a challenge increasingly relevant as artificial intelligence learns from scientific literature.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"1076-1078"},"PeriodicalIF":24.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148892480","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
Emerging STAT1 post-translational modifications: mechanisms and translational perspectives. 新出现的STAT1翻译后修饰：机制和翻译观点。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-10-01 Epub Date: 2026-09-08 DOI: 10.1016/j.tips.2026.08.014
Suyeol Im, So Eun Lee, Bumseok Kim, Seung Pil Yun, Jong-Won Kim
{"title":"Emerging STAT1 post-translational modifications: mechanisms and translational perspectives.","authors":"Suyeol Im, So Eun Lee, Bumseok Kim, Seung Pil Yun, Jong-Won Kim","doi":"10.1016/j.tips.2026.08.014","DOIUrl":"10.1016/j.tips.2026.08.014","url":null,"abstract":"<p><p>Signal transducer and activator of transcription 1 (STAT1) is a central regulator of interferon signaling, antiviral defense, inflammation, and antitumor immunity. Although STAT1 activation has been traditionally defined by phosphorylation, recent studies have revealed diverse post-translational modifications (PTMs) that fine-tune its activity, stability, localization, and transcriptional output. Newly identified modifications, including vitamin C-derived vitcylation and pyruvate-induced pyruvylation, directly link nutrient and metabolic cues to STAT1 signaling. Additional PTMs, such as acylation, glycosylation, ubiquitination, methylation, and oxidative modifications, further shape STAT1 function in a context-dependent manner. In this review, we evaluate the evidence supporting STAT1 PTMs and discuss how specific modifications regulate STAT1 activation, stability, localization, and transcriptional output in immune and inflammatory contexts, while distinguishing established regulatory mechanisms from emerging modifications that require further validation.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"1136-1154"},"PeriodicalIF":24.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148913434","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
Nitroxyl (HNO) therapeutics: exposure control and target engagement. 硝基（HNO）疗法：暴露控制和靶标接合。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-10-01 Epub Date: 2026-09-09 DOI: 10.1016/j.tips.2026.08.010
Sebastián A Suarez
{"title":"Nitroxyl (HNO) therapeutics: exposure control and target engagement.","authors":"Sebastián A Suarez","doi":"10.1016/j.tips.2026.08.010","DOIUrl":"10.1016/j.tips.2026.08.010","url":null,"abstract":"<p><p>Nitroxyl (HNO) donors enhance cardiac contraction and relaxation. However, systemic administration of these donors provides limited control over local HNO exposure or interaction with the target. This forum discusses recent approaches and challenges to control HNO generation, reshape exposure, and assess target engagement, evaluating mechanisms, maturity, constraints, and therapeutic fit.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"1079-1084"},"PeriodicalIF":24.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148913468","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
Dissecting the Lewy body. 解剖路易体。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-10-01 Epub Date: 2026-09-03 DOI: 10.1016/j.tips.2026.08.007
Emanuele Frattini, Jens C Schwamborn
{"title":"Dissecting the Lewy body.","authors":"Emanuele Frattini, Jens C Schwamborn","doi":"10.1016/j.tips.2026.08.007","DOIUrl":"10.1016/j.tips.2026.08.007","url":null,"abstract":"<p><p>How Lewy pathology forms and diversifies remains a central question in Parkinson's disease research. A recent study by Mahul-Mellier and Colleagues proposes a dynamic model in which inclusion maturation and organelle remodeling drive pathological heterogeneity, reshaping concepts of disease mechanisms and providing new perspectives on therapeutic approaches.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"1072-1075"},"PeriodicalIF":24.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148888308","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
Bias from within: intracellular allosterism and the ICL2 hub. 内部偏倚：细胞内变构和ICL2中枢。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-10-01 Epub Date: 2026-09-16 DOI: 10.1016/j.tips.2026.08.015
Yang Zhou, Alan Long, Joshua D Gross, Lawrence S Barak, Alem W Kahsai
{"title":"Bias from within: intracellular allosterism and the ICL2 hub.","authors":"Yang Zhou, Alan Long, Joshua D Gross, Lawrence S Barak, Alem W Kahsai","doi":"10.1016/j.tips.2026.08.015","DOIUrl":"10.1016/j.tips.2026.08.015","url":null,"abstract":"<p><p>Targeting the orthosteric site of G protein-coupled receptors (GPCRs) has long dominated drug discovery, but intracellular allosteric modulators (AMs) provide new avenues to enhance selectivity and fine-tune signaling. Recent structural advances have illuminated intracellular allosteric pockets that act as conformational control hubs for transducer-selective engagement, biased signaling, and noncanonical receptor activation. Among these, the transmembrane helix 3 (TM3)-intracellular loop 2 (ICL2)-TM4 intracellular pocket (hereafter, the ICL2 site) has emerged as a key determinant of GPCR signaling bias and a strategic target for intracellular AM development. We review emerging structure-activity relationships, mechanistic and evolutionary determinants of ICL2-targeted intracellular allostery, and key translational challenges including membrane accessibility, pharmacokinetics, and species divergence. Finally, we highlight structure-guided and affinity-based discovery strategies for engineering pathway-selective intracellular AMs with greater transducer control than conventional orthosteric ligands.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"1155-1170"},"PeriodicalIF":24.0,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148983681","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 CH25H restores p62-mediated α-synuclein clearance. 靶向CH25H恢复p62介导的α-突触核蛋白清除。
IF 24 1区 医学
Trends in pharmacological sciences Pub Date : 2026-09-28 DOI: 10.1016/j.tips.2026.09.002
Gavin S Dawe
{"title":"Targeting CH25H restores p62-mediated α-synuclein clearance.","authors":"Gavin S Dawe","doi":"10.1016/j.tips.2026.09.002","DOIUrl":"https://doi.org/10.1016/j.tips.2026.09.002","url":null,"abstract":"<p><p>Astrocytes remove extracellular α-synuclein aggregates through p62-dependent autophagy, yet the factors limiting this defense remain unclear. Zhang and colleagues recently identified cholesterol 25-hydroxylase as an inducible negative regulator of p62-mediated clearance. Genetic suppression or a p62-derived decoy peptide reduced α-synuclein pathology in mouse models of Parkinson's disease.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":""},"PeriodicalIF":24.0,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149075856","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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