The impact of genomics-based technologies on drug safety evaluation.

abstract：:Development 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 ov...

journal_title：Annual review of pharmacology and toxicology

authors： Snyder SH

更新日期：2017-01-06 00:00:00

abstract：:The theme "New Approaches for Studying Drug and Toxicant Action: Applications to Drug Discovery and Development" links 13 articles in this volume of the Annual Review of Pharmacology and Toxicology (ARPT). The engaging prefatory articles by Arthur Cho and Robert Lefkowitz set the stage for this theme and for the revie...

journal_title：Annual review of pharmacology and toxicology

authors： Insel PA,Amara SG,Blaschke TF,Meyer UA

更新日期：2018-01-06 00:00:00

abstract：:The cost of drugs is a major and rapidly rising component of health-care expenditures. We survey recent literature on the ethics and economics of skyrocketing pharmaceutical prices and find that advances in economic research have increased the sharpness and focus of the ethically based calls to increase access by modi...

journal_title：Annual review of pharmacology and toxicology

authors： Parker-Lue S,Santoro M,Koski G

更新日期：2015-01-01 00:00:00

abstract：:Exposure of the developing conceptus to selected environmental agents can lead to deleterious and often times lethal birth defects. These malformations result in serious emotional and financial consequences to families and societies worldwide. As we continue to progress technologically, we face challenges from the int...

journal_title：Annual review of pharmacology and toxicology

authors： Finnell RH,Waes JG,Eudy JD,Rosenquist TH

更新日期：2002-01-01 00:00:00

abstract：:Apoptosis signal-regulating kinase 1 (ASK1) is a mitogen-activated protein kinase (MAPK) kinase kinase of the c-Jun N-terminal kinase (JNK) and p38 MAPK pathways. ASK1 is preferentially activated by various cytotoxic stressors and plays pivotal roles in a wide variety of cellular response to them. Recent analyses of A...

journal_title：Annual review of pharmacology and toxicology

authors： Takeda K,Noguchi T,Naguro I,Ichijo H

更新日期：2008-01-01 00:00:00

abstract：:Pluripotent stem cells (PSCs) are a potential replacement tissue source for degenerative diseases. Age-related macular degeneration (AMD) is a blinding disease triggered by degeneration of the retinal pigment epithelium (RPE), a monolayer tissue that functionally supports retinal photoreceptors. Recently published cli...

journal_title：Annual review of pharmacology and toxicology

authors： Sharma R,Bose D,Maminishkis A,Bharti K

更新日期：2020-01-06 00:00:00

abstract：:Retinoids regulate gene transcription by binding to the nuclear receptors, the retinoic acid (RA) receptors (RARs), and the retinoid X receptors (RXRs). RARs and RXRs are ligand-activated transcription factors for the regulation of RA-responsive genes. The actions of RARs and RXRs on gene transcription require a highl...

journal_title：Annual review of pharmacology and toxicology

authors： Wei LN

更新日期：2003-01-01 00:00:00

abstract：:The protein variously named ABCG2/BCRP/MXR/ABCP is a recently described ATP-binding cassette (ABC) transporter originally identified by its ability to confer drug resistance that is independent of Mrp1 (multidrug-resistance protein 1) and Pgp (P-glycoprotein). Unlike Mrp1 and Pgp, ABCG2 is a half-transporter that must...

journal_title：Annual review of pharmacology and toxicology

authors： Krishnamurthy P,Schuetz JD

更新日期：2006-01-01 00:00:00

abstract：:Mechanism-based PK-PD models differ from conventional PK-PD models in that they contain specific expressions to characterize, in a quantitative manner, processes on the causal path between drug administration and effect. This includes target site distribution, target binding and activation, pharmacodynamic interaction...

journal_title：Annual review of pharmacology and toxicology

authors： Danhof M,de Jongh J,De Lange EC,Della Pasqua O,Ploeger BA,Voskuyl RA

更新日期：2007-01-01 00:00:00

abstract：:Cyclooxygenase (COX), first purified in 1976 and cloned in 1988, is the key enzyme in the synthesis of prostaglandins (PGs) from arachidonic acid. In 1991, several laboratories identified a product from a second gene with COX activity and called it COX-2. However, COX-2 was inducible, and the inducing stimuli included...

journal_title：Annual review of pharmacology and toxicology

authors： Vane JR,Bakhle YS,Botting RM

更新日期：1998-01-01 00:00:00

abstract：:The major concepts presented in this review can be summarized as follows: 1. There is a multidirectional continuum of anesthetic states--some represented by CNS excitation and others by depression. 2. The reticular activating system is influenced by all anesthetics; some inhibit its action (stage III) and some hyperex...

journal_title：Annual review of pharmacology and toxicology

authors： Winters WD

更新日期：1976-01-01 00:00:00

abstract：:In this review, we discuss the potential pharmacological targeting of a set of powerful epigenetic mechanisms: DNA methylation control systems in the central nervous system (CNS). Specifically, we focus on the possible use of these targets for novel future treatments for learning and memory disorders. We first describ...

journal_title：Annual review of pharmacology and toxicology

authors： Day JJ,Kennedy AJ,Sweatt JD

更新日期：2015-01-01 00:00:00

abstract：:G protein-coupled receptors (GPCRs) represent a major class of proteins in the genome of many species, including humans. In addition to the mapping of a number of human disorders to regions of the genome containing GPCRs, a growing body of literature has documented frequently occurring variations (i.e. polymorphisms) ...

journal_title：Annual review of pharmacology and toxicology

authors： Rana BK,Shiina T,Insel PA

更新日期：2001-01-01 00:00:00

abstract：:Most facets of mammalian physiology and behavior vary according to time of day, thanks to endogenous circadian clocks. Therefore, it is not surprising that many aspects of pharmacology and toxicology also oscillate according to the same 24-h clocks. Daily oscillations in abundance of proteins necessary for either drug...

journal_title：Annual review of pharmacology and toxicology

authors： Dallmann R,Brown SA,Gachon F

更新日期：2014-01-01 00:00:00

abstract：:CB1 and CB2 cannabinoid receptors are the primary targets of endogenous cannabinoids (endocannabinoids). These G protein-coupled receptors play an important role in many processes, including metabolic regulation, craving, pain, anxiety, bone growth, and immune function. Cannabinoid receptors can be engaged directly by...

journal_title：Annual review of pharmacology and toxicology

authors： Mackie K

更新日期：2006-01-01 00:00:00

abstract：:Parkinson's disease (PD) is a chronic, progressive, disabling neurodegenerative disorder that begins in mid to late life and is characterized by motor impairment, autonomic dysfunction, and, in many, psychological and cognitive changes. Recent advances have helped delineate pathogenetic mechanisms, yet the cause of PD...

journal_title：Annual review of pharmacology and toxicology

authors： Goldman SM

更新日期：2014-01-01 00:00:00

abstract：:Neuroglial cells of the central nervous system include the astrocytes, oligodendrocytes, and microglia. Their counterparts in the peripheral nervous system are the Schwann cells. The term neuroglia comes from an erroneous concept originally coined by Virchow (1850), in which he envisioned the neurons to be embedded in...

journal_title：Annual review of pharmacology and toxicology

authors： Aschner M,Allen JW,Kimelberg HK,LoPachin RM,Streit WJ

更新日期：1999-01-01 00:00:00

abstract：:Billions of US dollars are invested every year by the pharmaceutical industry in drug development, with the aim of introducing new drugs that are effective and have minimal side effects. Thirty percent of in-pipeline drugs are excluded in an early phase of preclinical and clinical screening owing to cardiovascular saf...

journal_title：Annual review of pharmacology and toxicology

authors： Magdy T,Schuldt AJT,Wu JC,Bernstein D,Burridge PW

更新日期：2018-01-06 00:00:00

abstract：:Numerous lines of evidence demonstrate that calpains, a family of 14 Ca(2+)-activated neutral cysteine proteases, are involved in oncotic cell death in a variety of models. At this time, the biochemistry of most calpains and the specific roles of different calpains in physiology and pathology remain to be determined. ...

journal_title：Annual review of pharmacology and toxicology

authors： Liu X,Van Vleet T,Schnellmann RG

更新日期：2004-01-01 00:00:00

abstract：:The developing central nervous system (CNS) is more vulnerable to injury than the adult one. Although a great deal of research has been devoted to subtle effects of developmental exposure, such as neurobehavioral changes, this review instead focuses on a number of chemicals that have been shown, in several experimenta...

journal_title：Annual review of pharmacology and toxicology

authors： Costa LG,Aschner M,Vitalone A,Syversen T,Soldin OP

更新日期：2004-01-01 00:00:00

abstract：:Electron cryo-microscopy (cryo-EM) has revolutionized structure determination of membrane proteins and holds great potential for structure-based drug discovery. Here we discuss the potential of cryo-EM in the rational design of therapeutics for membrane proteins compared to X-ray crystallography. We also detail recent...

journal_title：Annual review of pharmacology and toxicology

authors： García-Nafría J,Tate CG

更新日期：2020-01-06 00:00:00

abstract：:Nuclear receptors (NR) are ligand-modulated transcription factors that play diverse roles in cell differentiation, development, proliferation, and metabolism and are associated with numerous liver pathologies such as cancer, steatosis, inflammation, fibrosis, cholestasis, and xenobiotic/drug-induced liver injury. The ...

journal_title：Annual review of pharmacology and toxicology

authors： Rudraiah S,Zhang X,Wang L

更新日期：2016-01-01 00:00:00

abstract：:Long-acting contraceptives are the most effective reversible contraceptive methods. Increasing patients' access to these contraceptives may translate into fewer unintended pregnancies and lead to substantial individual and public health benefits. However, development of long-acting products can be complex and challeng...

journal_title：Annual review of pharmacology and toxicology

authors： Li L,Tran D,Zhu H,Balimane P,Willett G,Zhao P,Gerrard SE,Vogelsong KM,Wang Y,Seo SK

更新日期：2021-01-06 00:00:00

abstract：:Recent studies of membrane transporters have revealed their importance in determining the pharmacokinetics of transporter substrates. When drug-drug interactions (DDIs) or genetic polymorphisms (i.e., pharmacogenetics) affect the activities of transporters, the pharmacokinetics of transporter substrate drugs is altere...

journal_title：Annual review of pharmacology and toxicology

authors： Yoshida K,Maeda K,Sugiyama Y

更新日期：2013-01-01 00:00:00

abstract：:Recent 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 hav...

journal_title：Annual review of pharmacology and toxicology

authors： Bennett CF,Baker BF,Pham N,Swayze E,Geary RS

更新日期：2017-01-06 00:00:00

abstract：:This essay is an account of the author's experience in trying to interpret the action of drugs as seen in in vitro bioassays. The central theme is how the development of simple mathematical models has assisted in the interpretation of drug actions. Starting from encounters with partial agonists, the essay describes th...

journal_title：Annual review of pharmacology and toxicology

authors： Black J

更新日期：1996-01-01 00:00:00

abstract：:The mammalian circadian system is organized in a hierarchical manner in that a central pacemaker in the suprachiasmatic nucleus (SCN) of the brain's hypothalamus synchronizes cellular circadian oscillators in most peripheral body cells. Fasting-feeding cycles accompanying rest-activity rhythms are the major timing cue...

journal_title：Annual review of pharmacology and toxicology

authors： Levi F,Schibler U

更新日期：2007-01-01 00:00:00

abstract：:Microbicides, substances applied topically to prevent sexual HIV infection, are needed to empower receptive sexual partners with effective prevention methods. Several large microbicide trials, however, failed to demonstrate efficacy, thus motivating a reevaluation of the current microbicide development paradigm, which...

journal_title：Annual review of pharmacology and toxicology

authors： Hendrix CW,Cao YJ,Fuchs EJ

更新日期：2009-01-01 00:00:00

abstract：:This article provides a personal account of the discovery of the induced synthesis of drug-metabolizing enzymes and of subsequent research that led to the discovery of multiple cytochromes P450 with different catalytic activities. The manuscript also emphasizes the role of environmental factors (in addition to genetic...

journal_title：Annual review of pharmacology and toxicology

authors： Conney AH

更新日期：2003-01-01 00:00:00

abstract：:The RNA polymerase I (Pol I) transcription machinery in the nucleolus is the key convergence point that collects and integrates a vast array of information from cellular signaling cascades to regulate ribosome production that in turn guides cell growth and proliferation. Cancer cells commonly harbor mutations that ina...

journal_title：Annual review of pharmacology and toxicology

authors： Drygin D,Rice WG,Grummt I

更新日期：2010-01-01 00:00:00