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

Molecular Activation of NLRP3 Inflammasome by Particles and Crystals: A Continuing Challenge of Immunology and Toxicology. 颗粒和晶体对 NLRP3 炎症体的分子激活：免疫学和毒理学的持续挑战。

IF 12.5 1区医学

Annual review of pharmacology and toxicology Pub Date : 2024-01-23 Epub Date: 2023-09-14 DOI: 10.1146/annurev-pharmtox-031023-125300

Qiang Ma, Chol Seung Lim

{"title":"Molecular Activation of NLRP3 Inflammasome by Particles and Crystals: A Continuing Challenge of Immunology and Toxicology.","authors":"Qiang Ma, Chol Seung Lim","doi":"10.1146/annurev-pharmtox-031023-125300","DOIUrl":"10.1146/annurev-pharmtox-031023-125300","url":null,"abstract":"Particles and crystals constitute a unique class of toxic agents that humans are constantly exposed to both endogenously and from the environment. Deposition of particulates in the body is associated with a range of diseases and toxicity. The mechanism by which particulates cause disease remains poorly understood due to the lack of mechanistic insights into particle-biological interactions. Recent research has revealed that many particles and crystals activate the NLRP3 inflammasome, an intracellular pattern-recognition receptor. Activated NLRP3 forms a supramolecular complex with an adaptor protein to activate caspase 1, which in turn activates IL-1β and IL-18 to instigate inflammation. Genetic ablation and pharmacological inhibition of the NLRP3 inflammasome dampen inflammatory responses to particulates. Nonetheless, how particulates activate NLRP3 remains a challenging question. From this perspective, we discuss our current understanding of and progress on revealing the function and mode of action of the NLRP3 inflammasome in mediating adaptive and pathologic responses to particulates in health and disease.","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":"417-433"},"PeriodicalIF":12.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10842595/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10233153","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

Anthracycline Toxicity: Light at the End of the Tunnel? 蒽环素毒性：隧道尽头的光？

IF 11.2 1区医学

Annual review of pharmacology and toxicology Pub Date : 2024-01-23 Epub Date: 2023-10-03 DOI: 10.1146/annurev-pharmtox-022823-035521

Romina B Cejas, Kateryna Petrykey, Yadav Sapkota, Paul W Burridge

{"title":"Anthracycline Toxicity: Light at the End of the Tunnel?","authors":"Romina B Cejas, Kateryna Petrykey, Yadav Sapkota, Paul W Burridge","doi":"10.1146/annurev-pharmtox-022823-035521","DOIUrl":"10.1146/annurev-pharmtox-022823-035521","url":null,"abstract":"Anthracycline-induced cardiotoxicity (AIC) is a serious and common side effect of anthracycline therapy. Identification of genes and genetic variants associated with AIC risk has clinical potential as a cardiotoxicity predictive tool and to allow the development of personalized therapies. In this review, we provide an overview of the function of known AIC genes identified by association studies and categorize them based on their mechanistic implication in AIC. We also discuss the importance of functional validation of AIC-associated variants in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) to advance the implementation of genetic predictive biomarkers. Finally, we review how patient-specific hiPSC-CMs can be used to identify novel patient-relevant functional targets and for the discovery of cardioprotectant drugs to prevent AIC. Implementation of functional validation and use of hiPSC-CMs for drug discovery will identify the next generation of highly effective and personalized cardioprotectants and accelerate the inclusion of approved AIC biomarkers into clinical practice.","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":"115-134"},"PeriodicalIF":11.2,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11260185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41105562","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

Deciphering Drug Targets and Actions with Single-Cell and Spatial Resolution. 以单细胞和空间分辨率解密药物靶点和作用。

IF 12.5 1区医学

Annual review of pharmacology and toxicology Pub Date : 2024-01-23 Epub Date: 2023-09-18 DOI: 10.1146/annurev-pharmtox-033123-123610

Zhengyuan Pang, Benjamin F Cravatt, Li Ye

{"title":"Deciphering Drug Targets and Actions with Single-Cell and Spatial Resolution.","authors":"Zhengyuan Pang, Benjamin F Cravatt, Li Ye","doi":"10.1146/annurev-pharmtox-033123-123610","DOIUrl":"10.1146/annurev-pharmtox-033123-123610","url":null,"abstract":"Recent advances in chemical, molecular, and genetic approaches have provided us with an unprecedented capacity to identify drug-target interactions across the whole proteome and genome. Meanwhile, rapid developments of single-cell and spatial omics technologies are revolutionizing our understanding of the molecular architecture of biological systems. However, a significant gap remains in how we align our understanding of drug actions, traditionally based on molecular affinities, with the in vivo cellular and spatial tissue heterogeneity revealed by these newer techniques. Here, we review state-of-the-art methods for profiling drug-target interactions and emerging multiomics tools to delineate the tissue heterogeneity at single-cell resolution. Highlighting the recent technical advances enabling high-resolution, multiplexable in situ small-molecule drug imaging (clearing-assisted tissue click chemistry, or CATCH), we foresee the integration of single-cell and spatial omics platforms, data, and concepts into the future framework of defining and understanding in vivo drug-target interactions and mechanisms of actions.","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":"507-526"},"PeriodicalIF":12.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10311190","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

Alcohol Use Disorder Treatment: Problems and Solutions. 酒精使用障碍治疗：问题与解决方案。

IF 12.5 1区医学

Annual review of pharmacology and toxicology Pub Date : 2024-01-23 DOI: 10.1146/annurev-pharmtox-031323-115847

George F Koob

{"title":"Alcohol Use Disorder Treatment: Problems and Solutions.","authors":"George F Koob","doi":"10.1146/annurev-pharmtox-031323-115847","DOIUrl":"10.1146/annurev-pharmtox-031323-115847","url":null,"abstract":"Alcohol use disorder (AUD) afflicts over 29 million individuals and causes more than 140,000 deaths annually in the United States. A heuristic framework for AUD includes a three-stage cycle-binge/intoxication, withdrawal/negative affect, and preoccupation/anticipation-that provides a starting point for exploring the heterogeneity of AUD with regard to treatment. Effective behavioral health treatments and US Food and Drug Administration-approved medications are available but greatly underutilized, creating a major treatment gap. This review outlines challenges that face the alcohol field in closing this treatment gap and offers solutions, including broadening end points for the approval of medications for the treatment of AUD; increasing the uptake of screening, brief intervention, and referral to treatment; addressing stigma; implementing a heuristic definition of recovery; engaging early treatment; and educating health-care professionals and the public about challenges that are associated with alcohol misuse. Additionally, this review focuses on broadening potential targets for the development of medications for AUD by utilizing the three-stage heuristic model of addiction that outlines domains of dysfunction in AUD and the mediating neurobiology of AUD.","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":"64 ","pages":"255-275"},"PeriodicalIF":12.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139541418","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

Introduction to the Theme "Pharmacological Individuality: New Insights and Strategies for Personalized and Precise Drug Treatment". “药理学个性化：个性化和精确药物治疗的新见解和策略”主题简介。

IF 12.5 1区医学

Annual review of pharmacology and toxicology Pub Date : 2023-10-10 DOI: 10.1146/annurev-pharmtox-090123-010552

Urs A Meyer, Susan G Amara, Terrence F Blaschke, Paul A Insel

{"title":"Introduction to the Theme \"Pharmacological Individuality: New Insights and Strategies for Personalized and Precise Drug Treatment\".","authors":"Urs A Meyer, Susan G Amara, Terrence F Blaschke, Paul A Insel","doi":"10.1146/annurev-pharmtox-090123-010552","DOIUrl":"https://doi.org/10.1146/annurev-pharmtox-090123-010552","url":null,"abstract":"The reviews in Volume 64 of the Annual Review of Pharmacology and Toxicology cover diverse topics. A common theme in many of the reviews is the interindividual variability in the clinical response to drugs. Highlighted areas include emerging developments in pharmacogenomics that can predict the personal risk for drug inefficacy and/or adverse drug reactions. Other reviews focus on the use of circulating biomarkers to define drug metabolism phenotypes and the effect of circadian regulation on drug response. Another emerging technology, digital twins that model individual patients, is used to generate computational simulations of drug effects and identify optimal personalized treatments. Another variable that may affect clinical outcomes, the nocebo response (an adverse reaction to a placebo), complicates clinical trials. These reviews further document that pharmacological individuality is an essential component of the concepts of personalized medicine and precision medicine and will likely have an important impact on patient care. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 64 is January 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":""},"PeriodicalIF":12.5,"publicationDate":"2023-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41231900","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

Introduction to the Theme “Pharmacological Individuality: New Insights and Strategies for Personalized and Precise Drug Treatment” 主题“药物个性:个性化和精准药物治疗的新见解和新策略”导论

1区医学

Annual review of pharmacology and toxicology Pub Date : 2023-10-10 DOI: 10.1146/annurev-physiol-090123-010552

Urs A. Meyer, Susan G. Amara, Terrence F. Blaschke, Paul A. Insel

{"title":"Introduction to the Theme “Pharmacological Individuality: New Insights and Strategies for Personalized and Precise Drug Treatment”","authors":"Urs A. Meyer, Susan G. Amara, Terrence F. Blaschke, Paul A. Insel","doi":"10.1146/annurev-physiol-090123-010552","DOIUrl":"https://doi.org/10.1146/annurev-physiol-090123-010552","url":null,"abstract":"The reviews in Volume 64 of the Annual Review of Pharmacology and Toxicology cover diverse topics. A common theme in many of the reviews is the interindividual variability in the clinical response to drugs. Highlighted areas include emerging developments in pharmacogenomics that can predict the personal risk for drug inefficacy and/or adverse drug reactions. Other reviews focus on the use of circulating biomarkers to define drug metabolism phenotypes and the effect of circadian regulation on drug response. Another emerging technology, digital twins that model individual patients, is used to generate computational simulations of drug effects and identify optimal personalized treatments. Another variable that may affect clinical outcomes, the nocebo response (an adverse reaction to a placebo), complicates clinical trials. These reviews further document that pharmacological individuality is an essential component of the concepts of personalized medicine and precision medicine and will likely have an important impact on patient care. Expected final online publication date for the Annual Review of Pharmacology and Toxicology, Volume 64 is January 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":"24 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136294071","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

Artificial Intelligence and Machine Learning for Lead-to-Candidate Decision-Making and Beyond. 人工智能和机器学习在候选人决策中的应用。

IF 12.5 1区医学

Annual review of pharmacology and toxicology Pub Date : 2023-01-20 DOI: 10.1146/annurev-pharmtox-051921-023255

Douglas McNair

{"title":"Artificial Intelligence and Machine Learning for Lead-to-Candidate Decision-Making and Beyond.","authors":"Douglas McNair","doi":"10.1146/annurev-pharmtox-051921-023255","DOIUrl":"https://doi.org/10.1146/annurev-pharmtox-051921-023255","url":null,"abstract":"The use of artificial intelligence (AI) and machine learning (ML) in pharmaceutical research and development has to date focused on research: target identification; docking-, fragment-, and motif-based generation of compound libraries; modeling of synthesis feasibility; rank-ordering likely hits according to structural and chemometric similarity to compounds having known activity and affinity to the target(s); optimizing a smaller library for synthesis and high-throughput screening; and combining evidence from screening to support hit-to-lead decisions. Applying AI/ML methods to lead optimization and lead-to-candidate (L2C) decision-making has shown slower progress, especially regarding predicting absorption, distribution, metabolism, excretion, and toxicology properties. The present review surveys reasons why this is so, reports progress that has occurred in recent years, and summarizes some of the issues that remain. Effective AI/ML tools to derisk L2C and later phases of development are important to accelerate the pharmaceutical development process, ameliorate escalating development costs, and achieve greater success rates.","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":"63 ","pages":"77-97"},"PeriodicalIF":12.5,"publicationDate":"2023-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10570891","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: 5

Structures of Leukotriene Biosynthetic Enzymes and Development of New Therapeutics. 白三烯生物合成酶的结构及新疗法的研究进展。

IF 12.5 1区医学

Annual review of pharmacology and toxicology Pub Date : 2023-01-20 DOI: 10.1146/annurev-pharmtox-051921-085014

Jesper Z Haeggström, Marcia E Newcomer

引用次数: 7

Pharmacological Induction of Granulocyte Cell Death as Therapeutic Strategy. 药物诱导粒细胞死亡作为治疗策略。

IF 12.5 1区医学

Annual review of pharmacology and toxicology Pub Date : 2023-01-20 DOI: 10.1146/annurev-pharmtox-051921-115130

Thomas Kaufmann, Hans-Uwe Simon

{"title":"Pharmacological Induction of Granulocyte Cell Death as Therapeutic Strategy.","authors":"Thomas Kaufmann, Hans-Uwe Simon","doi":"10.1146/annurev-pharmtox-051921-115130","DOIUrl":"https://doi.org/10.1146/annurev-pharmtox-051921-115130","url":null,"abstract":"Apoptosis is central for the maintenance of health. In the immune system, apoptosis guarantees proper development of immune cells and shutdown of immune reactions by the coordinated elimination of activated immune cells. Limitation of the life span of granulocytes is important, as overactivation of these cells is associated with chronic inflammation and collateral tissue damage. Consequently, targeted induction of granulocyte apoptosis may be beneficial in the course of respective immune disorders. Anti-inflammatory drugs such as glucocorticoids and monoclonal antibodies against IL-5Rα exert their function in part by triggering eosinophil apoptosis. Agonistic antibodies targeting Siglec-8 or death receptors are tested (pre)clinically. Moreover, a new class of inhibitors targeting antiapoptotic BCL-2 proteins shows great promise for anticancer treatments. Because of their specificity and tolerable side effects, these so-called BH3 mimetics may be worthwhile to evaluate in inflammatory disorders. Here, we review past and recent data on pharmacological apoptosis induction of granulocytes and highlight respective therapeutic potential.","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":"63 ","pages":"231-247"},"PeriodicalIF":12.5,"publicationDate":"2023-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9121203","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: 2

Fibroblast Growth Factor-Based Pharmacotherapies for the Treatment of Obesity-Related Metabolic Complications. 基于成纤维细胞生长因子的药物疗法治疗肥胖相关代谢并发症。

IF 12.5 1区医学

Annual review of pharmacology and toxicology Pub Date : 2023-01-20 DOI: 10.1146/annurev-pharmtox-032322-093904

Leigang Jin, Ranyao Yang, Leiluo Geng, Aimin Xu

{"title":"Fibroblast Growth Factor-Based Pharmacotherapies for the Treatment of Obesity-Related Metabolic Complications.","authors":"Leigang Jin, Ranyao Yang, Leiluo Geng, Aimin Xu","doi":"10.1146/annurev-pharmtox-032322-093904","DOIUrl":"https://doi.org/10.1146/annurev-pharmtox-032322-093904","url":null,"abstract":"The fibroblast growth factor (FGF) family, which comprises 22 structurally related proteins, plays diverse roles in cell proliferation, differentiation, development, and metabolism. Among them, two classical members (FGF1 and FGF4) and two endocrine members (FGF19 and FGF21) are important regulators of whole-body energy homeostasis, glucose/lipid metabolism, and insulin sensitivity. Preclinical studies have consistently demonstrated the therapeutic benefits of these FGFs for the treatment of obesity, diabetes, dyslipidemia, and nonalcoholic steatohepatitis (NASH). Several genetically engineered FGF19 and FGF21 analogs with improved pharmacodynamic and pharmacokinetic properties have been developed and progressed into various stages of clinical trials. These FGF analogs are effective in alleviating hepatic steatosis, steatohepatitis, and liver fibrosis in biopsy-confirmed NASH patients, whereas their antidiabetic and antiobesity effects are mildand vary greatly in different clinical trials. This review summarizes recent advances in biopharmaceutical development of FGF-based therapies against obesity-related metabolic complications, highlights major challenges in clinical implementation, and discusses possible strategies to overcome these hurdles.","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":"63 ","pages":"359-382"},"PeriodicalIF":12.5,"publicationDate":"2023-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9169482","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: 8