Drugs for allosteric sites on receptors.

abstract：:Selective, nonpeptide antagonists for tachykinin receptors first became available ten years ago. Of the three known tachykinin receptors, drug development has focused most intensively on the substance P-preferring receptor, neurokinin(1) (NK(1)). Although originally studied as potential analgesic compounds, recent evi...

journal_title：Annual review of pharmacology and toxicology

authors： Stout SC,Owens MJ,Nemeroff CB

更新日期：2001-01-01 00:00:00

abstract：:DNA topoisomerases are double-edged swords. They are essential for many vital functions of DNA during normal cell growth. However, they are also highly vulnerable under various physiological and nonphysiological stresses because of their delicate act on breaking and rejoining DNA. These stresses (e.g. exposure to topo...

journal_title：Annual review of pharmacology and toxicology

authors： Li TK,Liu LF

更新日期：2001-01-01 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：:Mutant ras oncogenes and alterations in the mitogenic signaling pathways that they regulate are associated with a wide variety of solid tumors and leukemias for which existing chemotherapeutics have limited utility. Of the possible approaches to inhibit Ras function, much attention has focused on a posttranslational m...

journal_title：Annual review of pharmacology and toxicology

authors： Gibbs JB,Oliff A

更新日期：1997-01-01 00:00:00

abstract：:γ-Secretases are a group of widely expressed, intramembrane-cleaving proteases involved in many physiological processes. Their clinical relevance comes from their involvement in Alzheimer's disease, cancer, and other disorders. A clinical trial with the wide-spectrum γ-secretase inhibitor semagacestat has, however, de...

journal_title：Annual review of pharmacology and toxicology

authors： De Strooper B,Chávez Gutiérrez L

更新日期：2015-01-01 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 renin-angiotensin-aldosterone system is one of the most important systems in cardiovascular control and in the pathogenesis of cardiovascular diseases. Therefore, it is already a very successful drug target for the therapy of these diseases. However, angiotensins are generated not only in the plasma but also local...

journal_title：Annual review of pharmacology and toxicology

authors： Bader M

更新日期：2010-01-01 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 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：:The Risk Assessment Committee of the European Chemicals Agency issued an opinion on classifying titanium dioxide (TiO2) as a suspected human carcinogen upon inhalation. Recent animal studies indicate that TiO2 may be carcinogenic through the oral route. There is considerable uncertainty on the carcinogenicity of TiO2,...

journal_title：Annual review of pharmacology and toxicology

authors： Braakhuis HM,Gosens I,Heringa MB,Oomen AG,Vandebriel RJ,Groenewold M,Cassee FR

更新日期：2021-01-06 00:00:00

abstract：:Human syndromes and mouse mutants that exhibit accelerated but bona fide aging in multiple organs and tissues have been invaluable for the identification of nine denominators of aging: telomere attrition, genome instability, epigenetic alterations, mitochondrial dysfunction, deregulated nutrient sensing, altered inter...

journal_title：Annual review of pharmacology and toxicology

authors： Vermeij WP,Hoeijmakers JH,Pothof J

更新日期：2016-01-01 00:00:00

abstract：:Both pharmacologic and genetic methods are now available to manipulate intracellular levels of the protein thiol metallothionein. These approaches have begun to reveal the protective roles metallothioneins (MTs) have against oxygen, nitrogen, and carbon-centered free radicals, as well as the contributory role of MT to...

journal_title：Annual review of pharmacology and toxicology

authors： Lazo JS,Pitt BR

更新日期：1995-01-01 00:00:00

abstract：:The application of rapid methods currently used for screening discovery drug candidates for metabolism and pharmacokinetic characteristics is discussed. General considerations are given for screening in this context, including the criteria for good screens, the use of counterscreens, the proper sequencing of screens, ...

journal_title：Annual review of pharmacology and toxicology

authors： White RE

更新日期：2000-01-01 00:00:00

abstract：:A number of exciting findings have been made in astrocytes during the past 15 years that have led many researchers to redefine how the brain works. Astrocytes are now widely regarded as cells that propagate Ca(2+) over long distances in response to stimulation, and, similar to neurons, release transmitters (called gli...

journal_title：Annual review of pharmacology and toxicology

authors： Fiacco TA,Agulhon C,McCarthy KD

更新日期：2009-01-01 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：: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：: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：: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：:The recognition that the wall tone of most arteries and veins can change in response to shear stress has several implications for our understanding of the effects of drugs on the circulation. By a primary action on the heart and vasculature, drugs can cause changes in cardiac output and blood pressure that lead to cha...

journal_title：Annual review of pharmacology and toxicology

authors： Bevan JA,Henrion D

更新日期：1994-01-01 00:00:00

abstract：:Arsenic is a naturally occurring metalloid and one of the few metals that can be metabolized inside the human body. The pervasive presence of arsenic in nature and anthropogenic sources from agricultural and medical use have perpetuated human exposure to this toxic and carcinogenic element. Highly exposed individuals ...

journal_title：Annual review of pharmacology and toxicology

authors： Chen QY,Costa M

更新日期：2021-01-06 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：: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

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：:The recent advances made in elucidating the processes of nociception have altered the way that chronic pain therapy and analgesic drug development are approached. Recent studies have highlighted new targets for drug discovery, including inhibition of inflammatory mediators (kinins, growth factors), newly expressed pro...

journal_title：Annual review of pharmacology and toxicology

authors： Dray A,Urban L

更新日期：1996-01-01 00:00:00

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：:Cyclic ADP-ribose (cADPR) and nicotinic acid adenine dinucleotide phosphate (NAADP) are two Ca(2+) messengers derived from NAD and NADP, respectively. Although NAADP is a linear molecule, structurally distinct from the cyclic cADPR, it is synthesized by similar enzymes, ADP-ribosyl cyclase and its homolog, CD38. The c...

journal_title：Annual review of pharmacology and toxicology

authors： Lee HC

更新日期：2001-01-01 00:00:00

abstract：:The beta 3 subtype of adrenaline and noradrenaline receptors has now been extensively characterized at the structural and functional levels. Ligand binding and adenylyl cyclase activation studies helped define a beta-adrenergic profile that is quite distinct from that of the beta 1- and beta 2-adrenergic receptors, bu...

journal_title：Annual review of pharmacology and toxicology

authors： Strosberg AD

更新日期：1997-01-01 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：: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：:Originally, 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, an...

journal_title：Annual review of pharmacology and toxicology

authors： Casida JE

更新日期：2017-01-06 00:00:00