Annual review of pharmacology and toxicology最新文献_第7页

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

Pharmacological Interventions in Labor and Delivery. 分娩中的药物干预。

IF 12.5 1区医学

Annual review of pharmacology and toxicology Pub Date : 2023-01-20 DOI: 10.1146/annurev-pharmtox-051921-122822

Susan Wray, Sarah Arrowsmith, Andrew Sharp

引用次数: 3

Understanding the Chemical Exposome During Fetal Development and Early Childhood: A Review. 了解胎儿发育和幼儿期化学物质暴露:综述。

IF 12.5 1区医学

Annual review of pharmacology and toxicology Pub Date : 2023-01-20 DOI: 10.1146/annurev-pharmtox-051922-113350

Magdaléna Krausová, Dominik Braun, Tina Buerki-Thurnherr, Claudia Gundacker, Eva Schernhammer, Lukas Wisgrill, Benedikt Warth

{"title":"Understanding the Chemical Exposome During Fetal Development and Early Childhood: A Review.","authors":"Magdaléna Krausová, Dominik Braun, Tina Buerki-Thurnherr, Claudia Gundacker, Eva Schernhammer, Lukas Wisgrill, Benedikt Warth","doi":"10.1146/annurev-pharmtox-051922-113350","DOIUrl":"https://doi.org/10.1146/annurev-pharmtox-051922-113350","url":null,"abstract":"Early human life is considered a critical window of susceptibility to external exposures. Infants are exposed to a multitude of environmental factors, collectively referred to as the exposome. The chemical exposome can be summarized as the sum of all xenobiotics that humans are exposed to throughout a lifetime. We review different exposure classes and routes that impact fetal and infant metabolism and the potential toxicological role of mixture effects. We also discuss the progress in human biomonitoring and present possiblemodels for studying maternal-fetal transfer. Data gaps on prenatal and infant exposure to xenobiotic mixtures are identified and include natural biotoxins, in addition to commonly reported synthetic toxicants, to obtain a more holistic assessment of the chemical exposome. We highlight the lack of large-scale studies covering a broad range of xenobiotics. Several recommendations to advance our understanding of the early-life chemical exposome and the subsequent impact on health outcomes are proposed.","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":"63 ","pages":"517-540"},"PeriodicalIF":12.5,"publicationDate":"2023-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10564763","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: 10

Cognitive Impairment Associated with Schizophrenia: From Pathophysiology to Treatment. 与精神分裂症相关的认知障碍:从病理生理学到治疗。

IF 12.5 1区医学

Annual review of pharmacology and toxicology Pub Date : 2023-01-20 DOI: 10.1146/annurev-pharmtox-051921-093250

Daniel C Javitt

{"title":"Cognitive Impairment Associated with Schizophrenia: From Pathophysiology to Treatment.","authors":"Daniel C Javitt","doi":"10.1146/annurev-pharmtox-051921-093250","DOIUrl":"https://doi.org/10.1146/annurev-pharmtox-051921-093250","url":null,"abstract":"Cognitive impairment is a core feature of schizophrenia and a major contributor to poor functional outcomes. Methods for assessment of cognitive dysfunction in schizophrenia are now well established. In addition, there has been increasing appreciation in recent years of the additional role of social cognitive impairment in driving functional outcomes and of the contributions of sensory-level dysfunction to higher-order impairments. At the neurochemical level, acute administration of N-methyl-d-aspartate receptor (NMDAR) antagonists reproduces the pattern of neurocognitive dysfunction associated with schizophrenia, encouraging the development of treatments targeted at both NMDAR and its interactome. At the local-circuit level, an auditory neurophysiological measure, mismatch negativity, has emerged both as a veridical index of NMDAR dysfunction and excitatory/inhibitory imbalance in schizophrenia and as a critical biomarker for early-stage translational drug development. Although no compounds have yet been approved for treatment of cognitive impairment associated with schizophrenia, several candidates are showing promise in early-phase testing.","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":"63 ","pages":"119-141"},"PeriodicalIF":12.5,"publicationDate":"2023-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10570682","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: 11

Biased Agonism: Lessons from Studies of Opioid Receptor Agonists. 偏倚激动作用:阿片受体激动剂研究的启示。

IF 12.5 1区医学

Annual review of pharmacology and toxicology Pub Date : 2023-01-20 DOI: 10.1146/annurev-pharmtox-052120-091058

Eamonn Kelly, Alexandra Conibear, Graeme Henderson

引用次数: 14

Introduction to the Theme "Development of New Drugs: Moving from the Bench to Bedside and Improved Patient Care". 介绍主题“新药的发展:从实验室到床边，改善病人护理”。

IF 12.5 1区医学

Annual review of pharmacology and toxicology Pub Date : 2023-01-20 DOI: 10.1146/annurev-pharmtox-091222-022612

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

{"title":"Introduction to the Theme \"Development of New Drugs: Moving from the Bench to Bedside and Improved Patient Care\".","authors":"Terrence F Blaschke, Paul A Insel, Susan G Amara, Urs A Meyer","doi":"10.1146/annurev-pharmtox-091222-022612","DOIUrl":"https://doi.org/10.1146/annurev-pharmtox-091222-022612","url":null,"abstract":"Investigations in pharmacology and toxicology range from molecular studies to clinical care. Studies in basic and clinical pharmacology and in preclinical and clinical toxicology are all essential in bringing new knowledge and new drugs into clinical use. The 30 reviews in Volume 63 of the Annual Review of Pharmacology and Toxicology explore topics across this spectrum. Examples include \"Zebrafish as a Mainstream Model for In Vivo Systems Pharmacology and Toxicology\" and \"Artificial Intelligence and Machine Learning for Lead-to-Candidate Decision-Making and Beyond.\" Other reviews discuss components important for drug discovery and development and the use of pharmaceuticals in a variety of diseases. Air pollution continues to increase globally; accordingly, \"Air Pollution-Related Neurotoxicity Across the Life Span\" is a timely and forward-thinking review. Volume 63 also explores the use of contemporary technologies such as electronic health records, pharmacogenetics, and new drug delivery systems that help enhance and improve the utility of new therapies.","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":"63 ","pages":"15-18"},"PeriodicalIF":12.5,"publicationDate":"2023-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10741368","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: 1