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Annual review of pharmacology and toxicology最新文献

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Possible Direction of Drug Discovery Based on Single-Molecule Live Imaging. 基于单分子实时成像的药物发现的可能方向。
IF 13.1 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2025-09-05 DOI: 10.1146/annurev-pharmtox-062624-025717
Hideaki Yoshimura, Takeaki Ozawa
{"title":"Possible Direction of Drug Discovery Based on Single-Molecule Live Imaging.","authors":"Hideaki Yoshimura, Takeaki Ozawa","doi":"10.1146/annurev-pharmtox-062624-025717","DOIUrl":"https://doi.org/10.1146/annurev-pharmtox-062624-025717","url":null,"abstract":"<p><p>In conventional drug discovery, particularly for small molecules, investigating a small compound that matches the structure of the target molecule and alters its activity has been a crucial process. On the other hand, artificially regulating the activity of a target molecule that is inherently present in cells or organisms and involved in a physiological function can cause various side effects. One possible approach to overcoming this side effect problem is to explore molecules that affect the behavior or motility of molecules related to diseases. If a screening method is developed to search for drugs that target only specific motions of the target molecules, a new concept of motility-targeted drug discovery will be created. In this review article, single-molecule live imaging -a core technology for analyzing the motility of molecules in living cells and organisms -is introduced by describing examples of single-molecule imaging, such as membrane receptors and RNAs. The potential of single-molecule imaging to contribute to drug discovery is also discussed.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145005890","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
Gβγ Signaling: Lessons Across the Cellular Multiverse. Gβγ信号：跨越细胞多元宇宙的经验教训。
IF 13.1 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2025-08-25 DOI: 10.1146/annurev-pharmtox-062124-033726
Sana Qayum, Darlaine Pétrin, Jason C Tanny, Terence E Hébert
{"title":"Gβγ Signaling: Lessons Across the Cellular Multiverse.","authors":"Sana Qayum, Darlaine Pétrin, Jason C Tanny, Terence E Hébert","doi":"10.1146/annurev-pharmtox-062124-033726","DOIUrl":"https://doi.org/10.1146/annurev-pharmtox-062124-033726","url":null,"abstract":"<p><p>The eponymous term Gβγ protein has given way to a more nuanced view of 60 different possible combinations of the 5 Gβ and 12 Gγ subunits and their effects on cellular signaling profiles. Beyond this increased appreciation of their diversity per se, we now know that distinct Gβγ combinations may play roles beyond the regulation of cell surface effectors following G protein-coupled receptor activation and release from G protein heterotrimers. Gβγ subunits operate in multiple subcellular compartments. In this review, we focus on Gβγ-mediated events in the endoplasmic reticulum, Golgi apparatus, and mitochondria and particularly highlight Gβγ roles in the nucleus.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144939367","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
Multisystem Toxicity of E-Cigarettes in Preclinical and Clinical Studies: Pathophysiologic Effects of E-Cigarette Aerosol Exposures from Head to Toe. 电子烟在临床前和临床研究中的多系统毒性：从头到脚暴露于电子烟气溶胶的病理生理效应。
IF 13.1 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2025-08-19 DOI: 10.1146/annurev-pharmtox-062124-022856
Matthew J Mears, Priya Bandaru, Evan W Neczypor, Min Kwang Byun, Michelle Zhang, Matthew W Gorr, Jorge A Masso-Silva, Laura Barnes, Alexia Perryman, Avnee Kumar, Jeffrey M Hendel, Ana Lucia Fuentes, Loren E Wold, Laura E Crotty Alexander
{"title":"Multisystem Toxicity of E-Cigarettes in Preclinical and Clinical Studies: Pathophysiologic Effects of E-Cigarette Aerosol Exposures from Head to Toe.","authors":"Matthew J Mears, Priya Bandaru, Evan W Neczypor, Min Kwang Byun, Michelle Zhang, Matthew W Gorr, Jorge A Masso-Silva, Laura Barnes, Alexia Perryman, Avnee Kumar, Jeffrey M Hendel, Ana Lucia Fuentes, Loren E Wold, Laura E Crotty Alexander","doi":"10.1146/annurev-pharmtox-062124-022856","DOIUrl":"10.1146/annurev-pharmtox-062124-022856","url":null,"abstract":"<p><p>The global population breathes unsafe levels of pollutants. In recent years, electronic cigarettes (e-cigs) have become a significant source of particulate matter (PM), which causes injurious effects across organ systems. E-cig users and bystanders are exposed to concentrated aerosols, commonly called vapor, that we now know can have harmful long-term consequences due to PM and chemicals contained within. E-cigs are diverse in design, and e-liquids vary dramatically, making it difficult to draw broad conclusions from studies of different devices, brands, and flavors. With the rise in popularity of e-cigs, it is important to define the health effects across the body. In this comprehensive review, we dissect and summarize the known organ-specific effects of e-cigs, including underlying molecular mechanisms. Notably, e-cig aerosols broadly cause increased cytokine release and oxidative stress, which are associated with a heightened risk of organ dysfunction. We also highlight ways to minimize harmful e-cig constituents to develop safer products.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144881925","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
Structural Insights into the Development of Inhibitors Against Cancer-Specific Mutations of PI3Kα. PI3Kα癌症特异性突变抑制剂的结构研究
IF 13.1 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2025-08-19 DOI: 10.1146/annurev-pharmtox-082924-022724
Xiao Liu, Yanyan Chen, Wei Han, Yan Chen, Wenbo Feng, Qingtong Zhou, Ming-Wei Wang
{"title":"Structural Insights into the Development of Inhibitors Against Cancer-Specific Mutations of PI3Kα.","authors":"Xiao Liu, Yanyan Chen, Wei Han, Yan Chen, Wenbo Feng, Qingtong Zhou, Ming-Wei Wang","doi":"10.1146/annurev-pharmtox-082924-022724","DOIUrl":"10.1146/annurev-pharmtox-082924-022724","url":null,"abstract":"<p><p>Phosphoinositide 3-kinase alpha (PI3Kα) is a pivotal regulator of cell growth, proliferation, and survival. Dysregulation of the PI3K/AKT/mTOR pathway, driven predominantly by <i>PIK3CA</i> mutations (e.g., H1047R, E542K, and E545K), is a hallmark of many cancers. Advances in structural, biochemical, and computational studies have elucidated mutation-specific conformational changes of PI3Kα. While early pan- and isoform-selective PI3K inhibitors (alpelisib) show clinical utility, their intrinsic toxicity and resistance to treatment persist. Recent breakthroughs include the emergence of allosteric inhibitors (RLY-2608 and STX-478) that exploit mutation-induced cryptic pockets to achieve mutant selectivity as well as covalent inhibitors and degraders (inavolisib) that enhance specificity, aiming at decoupling antitumor activity from metabolic dysfunction. This review synthesizes current progress in PI3Kα inhibitor development, emphasizing structural characteristics, clinical challenges, and emerging strategies. Addressing challenges to increase mutant selectivity, exploring conformational modulation, uncovering new mechanisms of action, and implementing personalized therapies are key future directions for PI3Kα-targeted drug discovery.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144881926","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
Dengue Fever Vaccines: Progress and Challenges. 登革热疫苗：进展和挑战。
IF 13.1 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2025-08-18 DOI: 10.1146/annurev-pharmtox-062124-040711
Alan L Rothman, Heather Friberg
{"title":"Dengue Fever Vaccines: Progress and Challenges.","authors":"Alan L Rothman, Heather Friberg","doi":"10.1146/annurev-pharmtox-062124-040711","DOIUrl":"10.1146/annurev-pharmtox-062124-040711","url":null,"abstract":"<p><p>Development of vaccines against dengue has been designated a priority for over 75 years. The completion of Phase III trials and licensing of multiple dengue vaccines have been significant accomplishments of the last 15 years. Despite that progress, a vaccine suitable for broad use has not yet been identified. The scientific challenges of multiple dengue viral serotypes, immune imprinting from previous infections, and immune enhancement of infection and disease remain formidable obstacles to this goal. Further investments in clinical research of natural dengue virus infections and participants in dengue vaccine trials will be needed to enable the development and testing of the next generation of dengue vaccines.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2025-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144871090","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
Biased Signaling in Psychedelic Action. 致幻剂作用中的偏倚信号。
IF 13.1 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2025-08-12 DOI: 10.1146/annurev-pharmtox-062124-012545
Daniel Wacker, John D McCorvy
{"title":"Biased Signaling in Psychedelic Action.","authors":"Daniel Wacker, John D McCorvy","doi":"10.1146/annurev-pharmtox-062124-012545","DOIUrl":"10.1146/annurev-pharmtox-062124-012545","url":null,"abstract":"<p><p>Psychedelics show tremendous promise for treating psychiatric disorders and other illnesses, including pain and migraine. Despite decades of research, there is uncertainty which signaling mechanisms are necessary for rapid-acting and durable therapeutic effects of psychedelics. Although activation of the serotonin 5-HT<sub>2A</sub> receptor is critical for their psychopharmacological effects, the precise signaling pathways and receptor conformations responsible are still under investigation. This review summarizes progress in studying 5-HT<sub>2A</sub> signaling mechanisms and recent developments in the discovery of biased agonist tool compounds to disentangle therapeutic from adverse effects. Moreover, we review insights from structural studies regarding the design of psychedelic-derived compounds with tailored pharmacology and briefly discuss other 5-HT receptors that may be important for shaping therapeutic effects. Finally, by drawing parallels between 5-HT<sub>2A</sub> biased signaling and the opioid field, we conclude with lessons learned and discuss the need for more rigor and reproducibility to facilitate the development of novel psychedelic-based pharmacotherapies.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833806","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
From Fundamental Biology to Toxicology by Way of an Accident. 从基础生物学到毒理学的一次意外。
IF 13.1 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2025-08-12 DOI: 10.1146/annurev-pharmtox-071724-100915
Ana M Soto
{"title":"From Fundamental Biology to Toxicology by Way of an Accident.","authors":"Ana M Soto","doi":"10.1146/annurev-pharmtox-071724-100915","DOIUrl":"https://doi.org/10.1146/annurev-pharmtox-071724-100915","url":null,"abstract":"<p><p>When I was young and pictured my future, it wasn't a path that could be determined a priori. The world was full of interesting things. Obtaining the qualifications to become a professor and a researcher was the easy part. The rest relied on being in the right place at the right moment and having the intuition to feel the importance of events we were witnessing. This is how I met my mentors and how my scientific partner and I came upon the paradox that caused us to propose the principle of biological inertia. This is also how we discovered that estrogens leached from plasticware were ruining our experiments, and thus we became \"toxicologists by accident.\" Indeed, we were never formally trained in pharmacology or toxicology; however, our discovery that the estrogen nonylphenol leached from plastics made us pioneers of the new field of endocrine disruptors that encompasses endocrinology and toxicology.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144833807","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
The Chemical Toxicology of Ambient Air Pollutants. 环境空气污染物的化学毒理学。
IF 13.1 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2025-08-05 DOI: 10.1146/annurev-pharmtox-021025-091036
Arthur K Cho, Yoshito Kumagai, Yumi Abiko
{"title":"The Chemical Toxicology of Ambient Air Pollutants.","authors":"Arthur K Cho, Yoshito Kumagai, Yumi Abiko","doi":"10.1146/annurev-pharmtox-021025-091036","DOIUrl":"https://doi.org/10.1146/annurev-pharmtox-021025-091036","url":null,"abstract":"<p><p>Many of the adverse effects of ambient air pollution have been attributed to reactions of chemical species generated from fossil or biogenic fuel combustion. This review focuses on two reactions: (<i>a</i>) a prooxidant reaction, in which oxygen is reduced to hydrogen peroxide, and (<i>b</i>) covalent bond formation between electron-rich centers on biological targets with reactive compounds called electrophiles. Prooxidants were found to be concentrated in the particulate matter (PM) fraction of ambient air in the Los Angeles Basin with electrophiles concentrated in the volatile organic compound (VOC) fractions. Actions on mouse macrophages indicated the adverse effects to be mostly attributed to the PM, with anti-inflammatory actions to the VOC fraction. The latter observation does not include, however, the adverse effects of VOCs associated with the transient receptor potential (TRP) calcium channels on epithelial cells, a perspective that needs further investigation.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144788107","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
Community Aspects of HIV Biomedical Prevention. 艾滋病毒生物医学预防的社区方面。
IF 13.1 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2025-07-31 DOI: 10.1146/annurev-pharmtox-062124-044855
Bruno Spire, Marion di Ciaccio
{"title":"Community Aspects of HIV Biomedical Prevention.","authors":"Bruno Spire, Marion di Ciaccio","doi":"10.1146/annurev-pharmtox-062124-044855","DOIUrl":"https://doi.org/10.1146/annurev-pharmtox-062124-044855","url":null,"abstract":"<p><p>Although HIV treatment and prevention efforts in recent decades have significantly reduced new infections and mortality worldwide, progress has been uneven. Regions with the highest prevalence are those where HIV control programs fail to reach key populations, such as people who inject drugs, men who have sex with men, transgender people, and certain ethnic minorities. More specifically, the rollout of proven HIV prevention tools in these populations, such as antiretroviral therapy and pre-exposure prophylaxis, still presents a challenge. Community-based organizations play a key role in facilitating access to testing and treatment, particularly through rapid testing programs and peer support. These initiatives are crucial for overcoming social and cultural barriers, reducing stigma, and ensuring treatment adherence, especially among key populations.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758997","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
Pharmacological Mechanisms of Cellular Nanoparticles in Biological Neutralization. 细胞纳米颗粒在生物中和中的药理学机制。
IF 13.1 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2025-07-28 DOI: 10.1146/annurev-pharmtox-062124-015449
Lei Sun, Kailin Feng, Jiayuan Alex Zhang, Wei-Ting Shen, Weiwei Gao, Liangfang Zhang
{"title":"Pharmacological Mechanisms of Cellular Nanoparticles in Biological Neutralization.","authors":"Lei Sun, Kailin Feng, Jiayuan Alex Zhang, Wei-Ting Shen, Weiwei Gao, Liangfang Zhang","doi":"10.1146/annurev-pharmtox-062124-015449","DOIUrl":"https://doi.org/10.1146/annurev-pharmtox-062124-015449","url":null,"abstract":"<p><p>Biological neutralization refers to the process by which a biological agent, such as an antibody, enzyme, or therapeutic nanoparticle, renders a target molecule or pathogen harmless or inactive. Traditional approaches, such as antibody-based therapies, rely on precise molecular recognition, requiring customized development for each target. Recently, cell membrane-coated nanoparticles (cellular nanoparticles or CNPs), formulated by using natural cell membranes as drug substances, have emerged as a promising alternative. Acting as decoys, CNPs bind harmful agents based on membrane function rather than the molecular specificity, enabling broad-spectrum neutralization. This review examines how this fundamental pharmacological mechanism has guided CNP design to counteract pathological threats, including bacterial toxins, nerve agents, neurotoxins, inflammatory cytokines, autoantibodies, secretory enzymes, and viruses. Furthermore, we discuss strategies to enhance CNP performance through modifying the nanoparticle core or the membrane shell. By highlighting recent advancements, we aim to inspire further research into CNP-based approaches for tackling complex biological threats.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":""},"PeriodicalIF":13.1,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726870","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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