Annual Review of Pharmacology and Toxicology - Volume 57, 2017
Volume 57, 2017
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A Life of Neurotransmitters
Vol. 57 (2017), pp. 1–11More LessDevelopment of scientific creativity is often tied closely to mentorship. In my case, two years with Julius Axelrod, the sum total of my research training, was transformative. My mentoring generations of graduate students and postdoctoral fellows has been as nurturing for me as it has been for them. Work in our lab over fifty years has covered the breadth of neurotransmitters and related substances, focusing on the discove Read More
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Introduction to the Theme “New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology”
Vol. 57 (2017), pp. 13–17More LessMajor advances in scientific discovery and insights can result from the development and use of new techniques, as exemplified by the work of Solomon Snyder, who writes a prefatory article in this volume. The Editors have chosen “New Methods and Novel Therapeutic Approaches in Pharmacology and Toxicology” as the Theme for a number of articles in this volume. These include ones that review the development a Read More
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Nanobodies to Study G Protein–Coupled Receptor Structure and Function
Vol. 57 (2017), pp. 19–37More LessLigand-induced activation of G protein–coupled receptors (GPCRs) is a key mechanism permitting communication between cells and organs. Enormous progress has recently elucidated the structural and dynamic features of GPCR transmembrane signaling. Nanobodies, the recombinant antigen–binding fragments of camelid heavy-chain-only antibodies, have emerged as important research tools to lock GPCRs in particula Read More
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Strategies to Develop Inhibitors of Motif-Mediated Protein-Protein Interactions as Drug Leads
Vol. 57 (2017), pp. 39–60More LessProtein-protein interactions are fundamental for virtually all functions of the cell. A large fraction of these interactions involve short peptide motifs, and there has been increased interest in targeting them using peptide-based therapeutics. Peptides benefit from being specific, relatively safe, and easy to produce. They are also easy to modify using chemical synthesis and molecular biology techniques. However, significant challeng Read More
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Aptamers as Therapeutics
Vol. 57 (2017), pp. 61–79More LessAptamers are single-stranded nucleic acid molecules that bind to and inhibit proteins and are commonly produced by systematic evolution of ligands by exponential enrichment (SELEX). Aptamers undergo extensive pharmacological revision, which alters affinity, specificity, and therapeutic half-life, tailoring each drug for a specific clinical need. The first therapeutic aptamer was described 25 years ago. Thus far, one aptame Read More
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Pharmacology of Antisense Drugs
Vol. 57 (2017), pp. 81–105More LessRecent studies have led to a greater appreciation of the diverse roles RNAs play in maintaining normal cellular function and how they contribute to disease pathology, broadening the number of potential therapeutic targets. Antisense oligonucleotides are the most direct means to target RNA in a selective manner and have become an established platform technology for drug discovery. There are multiple molecular mechanisms Read More
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Targeted Protein Degradation by Small Molecules
Vol. 57 (2017), pp. 107–123More LessProtein homeostasis networks are highly regulated systems responsible for maintaining the health and productivity of cells. Whereas therapeutics have been developed to disrupt protein homeostasis, more recently identified techniques have been used to repurpose homeostatic networks to effect degradation of disease-relevant proteins. Here, we review recent advances in the use of small molecules to degrade proteins in a Read More
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Stem Cell Extracellular Vesicles: Extended Messages of Regeneration
Vol. 57 (2017), pp. 125–154More LessStem cells are critical to maintaining steady-state organ homeostasis and regenerating injured tissues. Recent intriguing reports implicate extracellular vesicles (EVs) as carriers for the distribution of morphogens and growth and differentiation factors from tissue parenchymal cells to stem cells, and conversely, stem cell–derived EVs carrying certain proteins and nucleic acids can support healing of injured tissues. We d Read More
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Accelerating Drug Development: Antiviral Therapies for Emerging Viruses as a Model
Vol. 57 (2017), pp. 155–169More LessDrug discovery and development is a lengthy and expensive process. Although no one, simple, single solution can significantly accelerate this process, steps can be taken to avoid unnecessary delays. Using the development of antiviral therapies as a model, we describe options for acceleration that cover target selection, assay development and high-throughput screening, hit confirmation, lead identification and dev Read More
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CNS Target Identification and Validation: Avoiding the Valley of Death or Naive Optimism?
P.H. Hutson, J.A. Clark, and A.J. CrossVol. 57 (2017), pp. 171–187More LessThere are many challenges along the path to the approval of new drugs to treat CNS disorders, one of the greatest areas of unmet medical need with a large societal burden and health-care impact. Unfortunately, over the past two decades, few CNS drug approvals have succeeded, leading many pharmaceutical companies to deprioritize this therapeutic area. The reasons for the failures in CNS drug discovery are likely to be Read More
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Innovative Approaches to Improve Anti-Infective Vaccine Efficacy
Vol. 57 (2017), pp. 189–222More LessSafe and efficacious vaccines are arguably the most successful medical interventions of all time. Yet the ongoing discovery of new pathogens, along with emergence of antibiotic-resistant pathogens and a burgeoning population at risk of such infections, imposes unprecedented public health challenges. To meet these challenges, innovative strategies to discover and develop new or improved anti-infective vaccines are necess Read More
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PCSK9: Regulation and Target for Drug Development for Dyslipidemia
Vol. 57 (2017), pp. 223–244More LessProprotein convertase subtilisin/kexin type-9 (PCSK9) is a secreted zymogen expressed primarily in the liver. PCSK9 circulates in plasma, binds to cell surface low-density lipoprotein (LDL) receptors, is internalized, and then targets the receptors to lysosomal degradation. Studies of naturally occurring PCSK9 gene variants that caused extreme plasma LDL cholesterol (LDL-C) deviations and altered atherosclerosis risk unleashe Read More
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Harnessing Big Data for Systems Pharmacology
Vol. 57 (2017), pp. 245–262More LessSystems pharmacology aims to holistically understand mechanisms of drug actions to support drug discovery and clinical practice. Systems pharmacology modeling (SPM) is data driven. It integrates an exponentially growing amount of data at multiple scales (genetic, molecular, cellular, organismal, and environmental). The goal of SPM is to develop mechanistic or predictive multiscale models that are interpretable and a Read More
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Changing Provider Behavior in the Context of Chronic Disease Management: Focus on Clinical Inertia
Vol. 57 (2017), pp. 263–283More LessWidespread acceptance of evidence-based medicine has led to the proliferation of clinical practice guidelines as the primary mode of communicating current best practices across a range of chronic diseases. Despite overwhelming evidence supporting the benefits of their use, there is a long history of poor uptake by providers. Nonadherence to clinical practice guidelines is referred to as clinical inertia and repr Read More
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Don't Worry, Be Happy: Endocannabinoids and Cannabis at the Intersection of Stress and Reward
Vol. 57 (2017), pp. 285–308More LessCannabis enables and enhances the subjective sense of well-being by stimulating the endocannabinoid system (ECS), which plays a key role in modulating the response to stress, reward, and their interactions. However, over time, repeated activation of the ECS by cannabis can trigger neuroadaptations that may impair the sensitivity to stress and reward. This effect, in vulnerable individuals, can lead to addiction and ot Read More
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Organophosphorus Xenobiotic Toxicology
Vol. 57 (2017), pp. 309–327More LessOriginally, organophosphorus (OP) toxicology consisted of acetylcholinesterase inhibition by insecticides and chemical threat agents acting as phosphorylating agents for serine in the catalytic triad, but this is no longer the case. Other serine hydrolases can be secondary OP targets, depending on the OP structure, and include neuropathy target esterase, lipases, and endocannabinoid hydrolases. The major OP herbici Read More
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Will There Be a Cure for Ebola?
Vol. 57 (2017), pp. 329–348More LessDespite the unprecedented Ebola virus outbreak response in West Africa, no Ebola medical countermeasures have been approved by the US Food and Drug Administration. However, multiple valuable lessons have been learned about the conduct of clinical research in a resource-poor, high risk–pathogen setting. Numerous therapeutics were explored or developed during the outbreak, including repurposed drugs, nucleoside Read More
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Challenges and Opportunities in Protease-Activated Receptor Drug Development
Vol. 57 (2017), pp. 349–373More LessProtease-activated receptors (PARs) are a unique class of G protein–coupled receptors (GPCRs) that transduce cellular responses to extracellular proteases. PARs have important functions in the vasculature, inflammation, and cancer and are important drug targets. A unique feature of PARs is their irreversible proteolytic mechanism of activation that results in the generation of a tethered ligand that cannot diffuse away. Despit Read More
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Autophagy: A Druggable Process
Vol. 57 (2017), pp. 375–398More LessMacroautophagy (hereafter called autophagy) is a vacuolar, lysosomal pathway for catabolism of intracellular material that is conserved among eukaryotic cells. Autophagy plays a crucial role in tissue homeostasis, adaptation to stress situations, immune responses, and the regulation of the inflammatory response. Blockade or uncontrolled activation of autophagy is associated with cancer, diabetes, obesity, cardiovascular di Read More
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Intestinal and Hepatocellular Transporters: Therapeutic Effects and Drug Interactions of Herbal Supplements
Vol. 57 (2017), pp. 399–416More LessHerbal supplements are generally considered safe; however, drug disposition is influenced by the interactions of herbal supplements and food constituents with transport and metabolic processes. Although the interference of herbal supplements with drug metabolism has been studied extensively, knowledge of how they interact with the drug transport processes is less advanced. Therefore, we describe here specific ex Read More
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Previous Volumes
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Volume 64 (2024)
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Volume 63 (2023)
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Volume 62 (2022)
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Volume 61 (2021)
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Volume 60 (2020)
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Volume 59 (2019)
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Volume 58 (2018)
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Volume 57 (2017)
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Volume 56 (2016)
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Volume 55 (2015)
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Volume 54 (2014)
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Volume 53 (2013)
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Volume 52 (2012)
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Volume 51 (2011)
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Volume 50 (2010)
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Volume 49 (2009)
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Volume 48 (2008)
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Volume 47 (2007)
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Volume 46 (2006)
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Volume 45 (2005)
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Volume 44 (2004)
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Volume 43 (2003)
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Volume 42 (2002)
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Volume 41 (2001)
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Volume 40 (2000)
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Volume 39 (1999)
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Volume 38 (1998)
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Volume 37 (1997)
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Volume 36 (1996)
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Volume 35 (1995)
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Volume 34 (1994)
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Volume 33 (1993)
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Volume 32 (1992)
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Volume 31 (1991)
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Volume 30 (1990)
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Volume 29 (1989)
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Volume 28 (1988)
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Volume 27 (1987)
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Volume 26 (1986)
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Volume 25 (1985)
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Volume 24 (1984)
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Volume 23 (1983)
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Volume 22 (1982)
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Volume 21 (1981)
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Volume 20 (1980)
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Volume 19 (1979)
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Volume 18 (1978)
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Volume 17 (1977)
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Volume 16 (1976)
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Volume 15 (1975)
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Volume 14 (1974)
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Volume 13 (1973)
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Volume 12 (1972)
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Volume 11 (1971)
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Volume 10 (1970)
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Volume 9 (1969)
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Volume 8 (1968)
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Volume 7 (1967)
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Volume 6 (1966)
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Volume 5 (1965)
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Volume 4 (1964)
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Volume 3 (1963)
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Volume 2 (1962)
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Volume 1 (1961)
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Volume 0 (1932)