Annual review of pharmacology and toxicology最新文献_第6页

Community Aspects of HIV Biomedical Prevention. 艾滋病毒生物医学预防的社区方面。

IF 19 1区医学

Annual review of pharmacology and toxicology Pub Date : 2026-01-01 Epub Date: 2025-07-31 DOI: 10.1146/annurev-pharmtox-062124-044855

Bruno Spire, Marion di Ciaccio

引用次数: 0

Microplastics and Atherosclerosis: Mechanisms. 微塑料与动脉粥样硬化：机制。

IF 19 1区医学

Annual review of pharmacology and toxicology Pub Date : 2026-01-01 DOI: 10.1146/annurev-pharmtox-062124-113011

Raffaele Marfella, Francesco Prattichizzo, Michelangela Barbieri, Pasquale Paolisso, Lucia Scisciola, Manuela Giovanna Basilicata, Ludovica Vittoria Marfella, Ada Pesapane, Angelo Fenti, Rosalba La Grotta, Francesca Carreras, Pasquale Iovino, Emanuele Barbato, Antonio Ceriello, Philip J Landrigan, Giuseppe Paolisso

{"title":"Microplastics and Atherosclerosis: Mechanisms.","authors":"Raffaele Marfella, Francesco Prattichizzo, Michelangela Barbieri, Pasquale Paolisso, Lucia Scisciola, Manuela Giovanna Basilicata, Ludovica Vittoria Marfella, Ada Pesapane, Angelo Fenti, Rosalba La Grotta, Francesca Carreras, Pasquale Iovino, Emanuele Barbato, Antonio Ceriello, Philip J Landrigan, Giuseppe Paolisso","doi":"10.1146/annurev-pharmtox-062124-113011","DOIUrl":"10.1146/annurev-pharmtox-062124-113011","url":null,"abstract":"Microplastics are emerging as mediators in the interaction between environmental pollutants and cardiovascular health. Micro- and nanoplastics (MNPs) can enter the human body through ingestion, inhalation, or skin exposure, disrupting biological processes such as autophagy, inflammation, oxidative stress, immune activation, and vascular dysfunction. Therefore, MNPs might promote the development of cardiovascular diseases. The link between MNPs and cardiovascular diseases remains unclear, with no consistent data confirming a correlation between their concentration in tissues and disease onset. Continuously evolving analytical techniques to detect MNPs within human organs and tissues will help the design of prospective studies detailing the possible harm provided by different microplastics as well as their effects according to their physical properties and associated chemicals. In this review, we provide an update on the existing techniques for MNP detection and characterization to summarize the mechanisms linking these pollutants to human health, focusing on their effects on the cardiovascular system.","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":"66 1","pages":"369-390"},"PeriodicalIF":19.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146040357","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 19 1区医学

Annual review of pharmacology and toxicology Pub Date : 2026-01-01 Epub 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":"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 PIK3CA 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.","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":"465-485"},"PeriodicalIF":19.0,"publicationDate":"2026-01-01","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

Human Mutations in the TRPV1 Channel: Implications for Noxious Cold Sensation. 人类TRPV1通道的突变：对有害冷感觉的影响。

IF 19 1区医学

Annual review of pharmacology and toxicology Pub Date : 2026-01-01 Epub Date: 2025-07-09 DOI: 10.1146/annurev-pharmtox-062624-025423

Ben Katz, Rita Gutorov, Channa Maayan, Rachel Zaguri, Baruch Minke

{"title":"Human Mutations in the TRPV1 Channel: Implications for Noxious Cold Sensation.","authors":"Ben Katz, Rita Gutorov, Channa Maayan, Rachel Zaguri, Baruch Minke","doi":"10.1146/annurev-pharmtox-062624-025423","DOIUrl":"10.1146/annurev-pharmtox-062624-025423","url":null,"abstract":"Sensing specific temperature ranges as noxious is crucial for protecting organisms from tissue damage. While the molecular detectors for noxious heat are well-characterized, those responsible for noxious cold detection remain elusive. The transient receptor potential vanilloid 1 (TRPV1) is a polymodal channel activated by heat, acid, and various animal and plant toxins. Due to its association with inflammatory pain, TRPV1 has become a promising target for analgesic development. A recent study reported on an individual carrying a homozygous TRPV1 mutation (N331K) that led to pronounced functional loss. Examination of the affected individual revealed an expected decrease in sensitivity to noxious heat and an unexpected increase in sensitivity to noxious cold. Furthermore, extensive neurogenic inflammatory, flare, and pain responses were observed following the application of a TRPA1 channel activator. These findings suggest that the combined activity of TRPV1 and TRPA1 is essential for controlling noxious cold sensitivity and should be considered when assessing TRPV1 pharmacology.","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":"405-417"},"PeriodicalIF":19.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144599209","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

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 19 1区医学

Annual review of pharmacology and toxicology Pub Date : 2026-01-01 Epub Date: 2025-09-05 DOI: 10.1146/annurev-pharmtox-062624-025717

Hideaki Yoshimura, Takeaki Ozawa

引用次数: 0

Pharmacogenetic Panel Testing: A Review of Current Practice and Potential for Clinical Implementation. 药物基因组测试：当前实践与临床实施潜力回顾。

IF 13.1 1区医学

Annual review of pharmacology and toxicology Pub Date : 2025-01-01 Epub Date: 2024-12-17 DOI: 10.1146/annurev-pharmtox-061724-080935

R Mosch, M van der Lee, H J Guchelaar, J J Swen

引用次数: 0

Evolving Approaches for Pharmacological Therapy of Obesity. 肥胖症药物治疗方法的演变。

IF 13.1 1区医学

Annual review of pharmacology and toxicology Pub Date : 2025-01-01 Epub Date: 2024-12-17 DOI: 10.1146/annurev-pharmtox-031124-101146

Ariana M Chao, Simeon Taylor, Molly Moore, Anastassia Amaro, Thomas A Wadden

引用次数: 0

Targeting Neuroplasticity in Substance Use Disorders: Implications for Therapeutics. 针对药物使用障碍的神经可塑性：对治疗的影响。

IF 13.1 1区医学

Annual review of pharmacology and toxicology Pub Date : 2025-01-01 Epub Date: 2024-12-17 DOI: 10.1146/annurev-pharmtox-061724-080548

Marina E Wolf

{"title":"Targeting Neuroplasticity in Substance Use Disorders: Implications for Therapeutics.","authors":"Marina E Wolf","doi":"10.1146/annurev-pharmtox-061724-080548","DOIUrl":"10.1146/annurev-pharmtox-061724-080548","url":null,"abstract":"The last two decades have witnessed substantial advances in identifying synaptic plasticity responsible for behavioral changes in animal models of substance use disorder. We have learned the most about cocaine-induced plasticity in the nucleus accumbens and its relationship to cocaine seeking, so that is the focus in this review. Synaptic plasticity pointing to potential therapeutic targets has been identified mainly using two drug self-administration models: extinction-reinstatement and abstinence models. A relationship between cocaine seeking and potentiated AMPAR transmission in nucleus accumbens is indicated by both models. In particular, an atypical subpopulation-Ca2+-permeable or CP-AMPARs-mediates cue-induced seeking that persists even after long periods of abstinence, modeling the persistent vulnerability to relapse that represents a major challenge in treating substance use disorder. We review strategies to reverse CP-AMPAR plasticity; strategies targeting other components of excitatory synapses, including dysregulated glutamate uptake and release; and behavioral interventions that can be augmented by harnessing synaptic plasticity.","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":"259-280"},"PeriodicalIF":13.1,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11864087/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387460","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

Toluene Toxicity in the Brain: From Cellular Targets to Molecular Mechanisms. 脑中的甲苯毒性：从细胞靶点到分子机制。

IF 19 1区医学

Annual review of pharmacology and toxicology Pub Date : 2025-01-01 DOI: 10.1146/annurev-pharmtox-012924-010532

Andrew A Shaw, Jeffery D Steketee, Anna N Bukiya, Alex M Dopico

{"title":"Toluene Toxicity in the Brain: From Cellular Targets to Molecular Mechanisms.","authors":"Andrew A Shaw, Jeffery D Steketee, Anna N Bukiya, Alex M Dopico","doi":"10.1146/annurev-pharmtox-012924-010532","DOIUrl":"10.1146/annurev-pharmtox-012924-010532","url":null,"abstract":"Toluene intoxication constitutes a persistent public health problem worldwide. While most organs can be damaged, the brain is a primary target whether exposure is accidental, occupational, or recreational. Interventions to prevent/revert brain damage by toluene are curtailed by the scarce information on the molecular targets and mechanisms mediating toluene's brain toxicity and the common exposure to other neurotoxins and/or coexistence of neurological/psychiatric disorders. We examine (a) the physicochemical properties of toluene that allow this inhalant to primarily target the lipid-rich brain; (b) the cell types targeted by toluene (neurons, different types of glia), while considering a cerebrovascular component; and (c) putative molecular mechanisms by which toluene may modify receptor function while analyzing structural features that allow toluene to directly interact with membrane lipids or specific proteins. This information constitutes a stepping stone to design pharmacotherapies that counteract toluene brain intoxication.","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":"65 1","pages":"487-506"},"PeriodicalIF":19.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12928535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027693","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

Progress and Challenges in the Field of Snakebite Envenoming Therapeutics. 蛇咬致病疗法领域的进展与挑战。

IF 13.1 1区医学

Annual review of pharmacology and toxicology Pub Date : 2025-01-01 Epub Date: 2024-12-17 DOI: 10.1146/annurev-pharmtox-022024-033544

José María Gutiérrez, Nicholas R Casewell, Andreas H Laustsen

引用次数: 0