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Annual review of pharmacology and toxicology最新文献

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Introduction to the Theme "Pharmacological Individuality: New Insights and Strategies for Personalized and Precise Drug Treatment". 药理学个体性：个性化和精准药物治疗的新见解和新策略 "主题介绍：个性化和精确药物治疗的新见解和新策略"。
IF 12.5 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-01-23 Epub 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":"10.1146/annurev-pharmtox-090123-010552","url":null,"abstract":"<p><p>The reviews in Volume 64 of the <i>Annual Review of Pharmacology and Toxicology</i> 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.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":"64 ","pages":"27-31"},"PeriodicalIF":12.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139519495","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
Addressing Ancestry and Sex Bias in Pharmacogenomics. 解决药物基因组学中的血统和性别偏见。
IF 12.5 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-01-23 Epub Date: 2023-07-14 DOI: 10.1146/annurev-pharmtox-030823-111731
Manuel Corpas, Moneeza K Siddiqui, Opeyemi Soremekun, Rohini Mathur, Dipender Gill, Segun Fatumo
{"title":"Addressing Ancestry and Sex Bias in Pharmacogenomics.","authors":"Manuel Corpas, Moneeza K Siddiqui, Opeyemi Soremekun, Rohini Mathur, Dipender Gill, Segun Fatumo","doi":"10.1146/annurev-pharmtox-030823-111731","DOIUrl":"10.1146/annurev-pharmtox-030823-111731","url":null,"abstract":"<p><p>The association of an individual's genetic makeup with their response to drugs is referred to as pharmacogenomics. By understanding the relationship between genetic variants and drug efficacy or toxicity, we are able to optimize pharmacological therapy according to an individual's genotype. Pharmacogenomics research has historically suffered from bias and underrepresentation of people from certain ancestry groups and of the female sex. These biases can arise from factors such as drugs and indications studied, selection of study participants, and methods used to collect and analyze data. To examine the representation of biogeographical populations in pharmacogenomic data sets, we describe individuals involved in gene-drug response studies from PharmGKB, a leading repository of drug-gene annotations, and showcase<i>CYP2D6</i>, a gene that metabolizes approximately 25% of all prescribed drugs. We also show how the historical underrepresentation of females in clinical trials has led to significantly more adverse drug reactions in females than in males.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":"53-64"},"PeriodicalIF":12.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9779570","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 Efferocytosis in Inflammaging. 在炎症过程中以吞噬细胞为目标
IF 12.5 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-01-23 Epub Date: 2023-08-16 DOI: 10.1146/annurev-pharmtox-032723-110507
Ivan K H Poon, Kodi S Ravichandran
{"title":"Targeting Efferocytosis in Inflammaging.","authors":"Ivan K H Poon, Kodi S Ravichandran","doi":"10.1146/annurev-pharmtox-032723-110507","DOIUrl":"10.1146/annurev-pharmtox-032723-110507","url":null,"abstract":"<p><p>Rapid removal of apoptotic cells by phagocytes, a process known as efferocytosis, is key for the maintenance of tissue homeostasis, the resolution of inflammation, and tissue repair. However, impaired efferocytosis can result in the accumulation of apoptotic cells, subsequently triggering sterile inflammation through the release of endogenous factors such as DNA and nuclear proteins from membrane permeabilized dying cells. Here, we review the molecular basis of the three key phases of efferocytosis, that is, the detection, uptake, and degradation of apoptotic materials by phagocytes. We also discuss how defects in efferocytosis due to the alteration of phagocytes and dying cells can contribute to the low-grade chronic inflammation that occurs during aging, described as inflammaging. Lastly, we explore opportunities in targeting and harnessing the efferocytic machinery to limit aging-associated inflammatory diseases.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":"339-357"},"PeriodicalIF":12.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10013250","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
Gene-Environment Interactions: My Unique Journey. 基因与环境的相互作用：我独特的旅程。
IF 12.5 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-022323-082311
Daniel W Nebert
{"title":"Gene-Environment Interactions: My Unique Journey.","authors":"Daniel W Nebert","doi":"10.1146/annurev-pharmtox-022323-082311","DOIUrl":"10.1146/annurev-pharmtox-022323-082311","url":null,"abstract":"<p><p>I am deeply honored to be invited to write this scientific autobiography. As a physician-scientist, pediatrician, molecular biologist, and geneticist, I have authored/coauthored more than 600 publications in the fields of clinical medicine, biochemistry, biophysics, pharmacology, drug metabolism, toxicology, molecular biology, cancer, standardized gene nomenclature, developmental toxicology and teratogenesis, mouse genetics, human genetics, and evolutionary genomics. Looking back, I think my career can be divided into four distinct research areas, which I summarize mostly chronologically in this article: (<i>a</i>) discovery and characterization of the AHR/CYP1 axis, (<i>b</i>) pharmacogenomics and genetic prediction of response to drugs and other environmental toxicants, (<i>c</i>) standardized drug-metabolizing gene nomenclature based on evolutionary divergence, and (<i>d</i>) discovery and characterization of the <i>SLC39A8</i> gene encoding the ZIP8 metal cation influx transporter. Collectively, all four topics embrace gene-environment interactions, hence the title of my autobiography.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":"1-26"},"PeriodicalIF":12.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41091887","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
G Protein-Coupled Receptor Signaling: New Insights Define Cellular Nanodomains. G 蛋白偶联受体信号：定义细胞纳米域的新见解。
IF 12.5 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-01-23 Epub Date: 2023-09-08 DOI: 10.1146/annurev-pharmtox-040623-115054
Martin J Lohse, Andreas Bock, Manuela Zaccolo
{"title":"G Protein-Coupled Receptor Signaling: New Insights Define Cellular Nanodomains.","authors":"Martin J Lohse, Andreas Bock, Manuela Zaccolo","doi":"10.1146/annurev-pharmtox-040623-115054","DOIUrl":"10.1146/annurev-pharmtox-040623-115054","url":null,"abstract":"<p><p>G protein-coupled receptors are the largest and pharmacologically most important receptor family and are involved in the regulation of most cell functions. Most of them reside exclusively at the cell surface, from where they signal via heterotrimeric G proteins to control the production of second messengers such as cAMP and IP<sub>3</sub> as well as the activity of several ion channels. However, they may also internalize upon agonist stimulation or constitutively reside in various intracellular locations. Recent evidence indicates that their function differs depending on their precise cellular localization. This is because the signals they produce, notably cAMP and Ca<sup>2+</sup>, are mostly bound to cell proteins that significantly reduce their mobility, allowing the generation of steep concentration gradients. As a result, signals generated by the receptors remain confined to nanometer-sized domains. We propose that such nanometer-sized domains represent the basic signaling units in a cell and a new type of target for drug development.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":"387-415"},"PeriodicalIF":12.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10187019","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 the Actions of Muscarinic Receptors on Dopamine Systems: New Strategies for Treating Neuropsychiatric Disorders. 针对多巴胺系统上的毒蕈碱受体的作用：治疗神经精神疾病的新策略。
IF 12.5 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-01-23 Epub Date: 2023-08-09 DOI: 10.1146/annurev-pharmtox-051921-023858
Eric J Nunes, Nii A Addy, P Jeffrey Conn, Daniel J Foster
{"title":"Targeting the Actions of Muscarinic Receptors on Dopamine Systems: New Strategies for Treating Neuropsychiatric Disorders.","authors":"Eric J Nunes, Nii A Addy, P Jeffrey Conn, Daniel J Foster","doi":"10.1146/annurev-pharmtox-051921-023858","DOIUrl":"10.1146/annurev-pharmtox-051921-023858","url":null,"abstract":"<p><p>Cholinergic regulation of dopamine (DA) signaling has significant implications for numerous disorders, including schizophrenia, substance use disorders, and mood-related disorders. The activity of midbrain DA neurons and DA release patterns in terminal regions are tightly regulated by cholinergic neurons found in both the striatum and the hindbrain. These cholinergic neurons can modulate DA circuitry by activating numerous receptors, including muscarinic acetylcholine receptor (mAChR) subtypes. This review specifically focuses on the complex role of M2, M4, and M5 mAChR subtypes in regulating DA neuron activity and DA release and the potential clinical implications of targeting these mAChR subtypes.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":"277-289"},"PeriodicalIF":12.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10841102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10219282","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
Novel Immunopharmacological Drugs for the Treatment of Allergic Diseases. 治疗过敏性疾病的新型免疫药理学药物。
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-051623-091038
Ekaterini Tiligada, Daria Gafarov, Maria Zaimi, Joana Vitte, Francesca Levi-Schaffer
{"title":"Novel Immunopharmacological Drugs for the Treatment of Allergic Diseases.","authors":"Ekaterini Tiligada, Daria Gafarov, Maria Zaimi, Joana Vitte, Francesca Levi-Schaffer","doi":"10.1146/annurev-pharmtox-051623-091038","DOIUrl":"10.1146/annurev-pharmtox-051623-091038","url":null,"abstract":"<p><p>The exponential rise in the prevalence of allergic diseases since the mid-twentieth century has led to a genuine public health emergency and has also fostered major progress in research on the underlying mechanisms and potential treatments. The management of allergic diseases benefits from the biological revolution, with an array of novel immunomodulatory therapeutic and investigational tools targeting players of allergic inflammation at distinct pathophysiological steps. Prominent examples include therapeutic monoclonal antibodies against cytokines, alarmins, and their receptors, as well as small-molecule modifiers of signal transduction mainly mediated by Janus kinases and Bruton's tyrosine kinases. However, the first-line therapeutic options have yet to switch from symptomatic to disease-modifying interventions. Here we present an overview of available drugs in the context of our current understanding of allergy pathophysiology, identify potential therapeutic targets, and conclude by providing a selection of candidate immunopharmacological molecules under investigation for potential future use in allergic diseases.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":"481-506"},"PeriodicalIF":12.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10311550","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
Direct K-Ras Inhibitors to Treat Cancers: Progress, New Insights, and Approaches to Treat Resistance. 直接使用 K-Ras 抑制剂治疗癌症：治疗癌症的直接 K-Ras 抑制剂：进展、新见解和治疗耐药性的方法》（Progress, New Insights, and Approaches to Treat Resistance.
IF 12.5 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-01-23 Epub Date: 2023-07-31 DOI: 10.1146/annurev-pharmtox-022823-113946
Ruth Nussinov, Hyunbum Jang
{"title":"Direct K-Ras Inhibitors to Treat Cancers: Progress, New Insights, and Approaches to Treat Resistance.","authors":"Ruth Nussinov, Hyunbum Jang","doi":"10.1146/annurev-pharmtox-022823-113946","DOIUrl":"10.1146/annurev-pharmtox-022823-113946","url":null,"abstract":"<p><p>Here we discuss approaches to K-Ras inhibition and drug resistance scenarios. A breakthrough offered a covalent drug against K-Ras<sup>G12C</sup>. Subsequent innovations harnessed same-allele drug combinations, as well as cotargeting K-Ras<sup>G12C</sup> with a companion drug to upstream regulators or downstream kinases. However, primary, adaptive, and acquired resistance inevitably emerge. The preexisting mutation load can explain how even exceedingly rare mutations with unobservable effects can promote drug resistance, seeding growth of insensitive cell clones, and proliferation. Statistics confirm the expectation that most resistance-related mutations are in <i>cis</i>, pointing to the high probability of cooperative, same-allele effects. In addition to targeted Ras inhibitors and drug combinations, bifunctional molecules and innovative tri-complex inhibitors to target Ras mutants are also under development. Since the identities and potential contributions of preexisting and evolving mutations are unknown, selecting a pharmacologic combination is taxing. Collectively, our broad review outlines considerations and provides new insights into pharmacology and resistance.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":"231-253"},"PeriodicalIF":12.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9902032","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
Health Digital Twins in Life Science and Health Care Innovation. 生命科学和医疗保健创新中的健康数字双胞胎。
IF 12.5 1区 医学
Annual review of pharmacology and toxicology Pub Date : 2024-01-23 Epub Date: 2023-08-10 DOI: 10.1146/annurev-pharmtox-022123-022046
Kaushik P Venkatesh, Gabriel Brito, Maged N Kamel Boulos
{"title":"Health Digital Twins in Life Science and Health Care Innovation.","authors":"Kaushik P Venkatesh, Gabriel Brito, Maged N Kamel Boulos","doi":"10.1146/annurev-pharmtox-022123-022046","DOIUrl":"10.1146/annurev-pharmtox-022123-022046","url":null,"abstract":"<p><p>Health digital twins (HDTs) are virtual representations of real individuals that can be used to simulate human physiology, disease, and drug effects. HDTs can be used to improve drug discovery and development by providing a data-driven approach to inform target selection, drug delivery, and design of clinical trials. HDTs also offer new applications into precision therapies and clinical decision making. The deployment of HDTs at scale could bring a precision approach to public health monitoring and intervention. Next steps include challenges such as addressing socioeconomic barriers and ensuring the representativeness of the technology based on the training and validation data sets. Governance and regulation of HDT technology are still in the early stages.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":"159-170"},"PeriodicalIF":12.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9964722","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
Translational In Vivo Assays in Behavioral Biology. 行为生物学的体内转化试验。
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-051921-093711
Sarah L Withey, Diego A Pizzagalli, Jack Bergman
{"title":"Translational In Vivo Assays in Behavioral Biology.","authors":"Sarah L Withey, Diego A Pizzagalli, Jack Bergman","doi":"10.1146/annurev-pharmtox-051921-093711","DOIUrl":"10.1146/annurev-pharmtox-051921-093711","url":null,"abstract":"<p><p>The failure of preclinical research to advance successful candidate medications in psychiatry has created a paradigmatic crisis in psychiatry. The Research Domain Criteria (RDoC) initiative was designed to remedy this situation with a neuroscience-based approach that employs multimodal and cross-species in vivo methodology to increase the probability of translational findings and, consequently, drug discovery. The present review underscores the feasibility of this methodological approach by briefly reviewing, first, the use of multidimensional and cross-species methodologies in traditional behavioral pharmacology and, subsequently, the utility of this approach in contemporary neuroimaging and electrophysiology research-with a focus on the value of functionally homologous studies in nonhuman and human subjects. The final section provides a brief review of the RDoC, with a focus on the potential strengths and weaknesses of its domain-based underpinnings. Optimistically, this mechanistic and multidimensional approach in neuropsychiatric research will lead to novel therapeutics for the management of neuropsychiatric disorders.</p>","PeriodicalId":8057,"journal":{"name":"Annual review of pharmacology and toxicology","volume":" ","pages":"435-453"},"PeriodicalIF":12.5,"publicationDate":"2024-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10233152","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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