Drug transporters in drug efficacy and toxicity.

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：: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：: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：: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：:Major 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 ...

journal_title：Annual review of pharmacology and toxicology

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

更新日期：2017-01-06 00:00:00

abstract：:Arterial tone is coordinated among vessel segments to optimize nutrient transport and organ function. Coordinated vasomotor activity is remarkable to observe and depends on stimuli, sparsely generated in tissue, eliciting electrical responses that conduct lengthwise among electrically coupled vascular cells. The condu...

journal_title：Annual review of pharmacology and toxicology

authors： Welsh DG,Tran CHT,Hald BO,Sancho M

更新日期：2018-01-06 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：: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：:Oral vaccination enables pain-free and self-administrable vaccine delivery for rapid mass vaccination during pandemic outbreaks. Furthermore, it elicits systemic and mucosal immune responses. This protects against infection at mucosal surfaces, which may further enhance protection and minimize the spread of disease. T...

journal_title：Annual review of pharmacology and toxicology

authors： Coffey JW,Gaiha GD,Traverso G

更新日期：2021-01-06 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：: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：:Research spanning (genetically engineered) animal models, healthy volunteers, and sleep-disordered patients has identified the neurotransmitters and neuromodulators dopamine, serotonin, norepinephrine, histamine, hypocretin, melatonin, glutamate, acetylcholine, γ-amino-butyric acid, and adenosine as important players ...

journal_title：Annual review of pharmacology and toxicology

authors： Holst SC,Valomon A,Landolt HP

更新日期：2016-01-01 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

abstract：:Systems approaches have long been used in pharmacology to understand drug action at the organ and organismal levels. The application of computational and experimental systems biology approaches to pharmacology allows us to expand the definition of systems pharmacology to include network analyses at multiple scales of ...

journal_title：Annual review of pharmacology and toxicology

authors： Zhao S,Iyengar R

更新日期：2012-01-01 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：: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：: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：: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 presence of druggable, topographically distinct allosteric sites on a wide range of receptor families has offered new paradigms for small molecules to modulate receptor function. Moreover, ligands that target allosteric sites offer significant advantages over the corresponding orthosteric ligands in terms of selec...

journal_title：Annual review of pharmacology and toxicology

authors： Wenthur CJ,Gentry PR,Mathews TP,Lindsley CW

更新日期：2014-01-01 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 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：: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：: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：:Oligonucleotides (ONs) can interfere with biomolecules representing the entire extended central dogma. Antisense gapmer, steric block, splice-switching ONs, and short interfering RNA drugs have been successfully developed. Moreover, antagomirs (antimicroRNAs), microRNA mimics, aptamers, DNA decoys, DNAzymes, synthetic...

journal_title：Annual review of pharmacology and toxicology

authors： Smith CIE,Zain R

更新日期：2019-01-06 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：:Ion channels and G protein-coupled receptors (GPCRs) are regulated by lipids in their membrane environment. Structural studies combined with biophysical and molecular simulation investigations reveal interaction sites for specific lipids on membrane protein structures. For K channels, PIP2 plays a key role in regulati...

journal_title：Annual review of pharmacology and toxicology

authors： Duncan AL,Song W,Sansom MSP

更新日期：2020-01-06 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：: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 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：: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