(Q36887542)

16 August 2017

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title

The application of discovery toxicology and pathology towards the design of safer pharmaceutical lead candidates (English)

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16 August 2017

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Jeffrey A Kramer

1

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16 August 2017

John E Sagartz

series ordinal

2

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16 August 2017

Dale L Morris

series ordinal

3

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16 August 2017

publication date

1 August 2007

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Nature Reviews Drug Discovery

16 August 2017

published in

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16 August 2017

volume

6

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16 August 2017

issue

8

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16 August 2017

page(s)

636-649

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Pharmaceutical innovation by the seven UK-owned pharmaceutical companies (1964-1985)

16 August 2017

cites work

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Revised methods for the Salmonella mutagenicity test

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21 January 2018

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The SOS chromotest: a review

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Yeast DEL assay detects clastogens

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Identification of a gene expression profile that discriminates indirect-acting genotoxins from direct-acting genotoxins

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The utility of DNA microarrays for characterizing genotoxicity

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Aberrant renal vascular morphology and renin expression in mutant mice lacking angiotensin-converting enzyme

21 January 2018

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Evidence for possible involvement of 5-HT(2B) receptors in the cardiac valvulopathy associated with fenfluramine and other serotonergic medications

21 January 2018

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In vivo detection of vascular adhesion protein-1 in experimental inflammation

21 January 2018

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Mechanisms and pathogenesis of thyroid cancer in animals and man.

21 January 2018

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Near completely humanized liver in mice shows human-type metabolic responses to drugs

21 January 2018

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Genetically engineered animals in drug discovery and development: a maturing resource for toxicologic research

21 January 2018

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Toxicogenomics in risk assessment: an overview of an HESI collaborative research program

21 January 2018

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Trends in development and approval times for new therapeutics in the United States

21 January 2018

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Prospects for productivity

31 March 2020

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The price of innovation: new estimates of drug development costs

31 March 2020

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Can the pharmaceutical industry reduce attrition rates?

31 March 2020

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Mass spectrometry in drug discovery: a current review

31 March 2020

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The pathologist and toxicologist in pharmaceutical product discovery

31 March 2020

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Concordance of the toxicity of pharmaceuticals in humans and in animals

31 March 2020

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First dose of potential new medicines to humans: how animals help

31 March 2020

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Safety assessment of biotechnology-derived pharmaceuticals: ICH and beyond

31 March 2020

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Prediction of chemical carcinogenicity in rodents from in vitro genetic toxicity assays.

31 March 2020

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A miniaturized Ames mutagenicity assay employing bioluminescent strains of Salmonella typhimurium.

31 March 2020

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An assessment of the utility of the yeast GreenScreen assay in pharmaceutical screening

31 March 2020

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The automated bone marrow micronucleus test

31 March 2020

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Flow cytometric analysis of micronucleated reticulocytes in mouse bone marrow

31 March 2020

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Automation of mouse micronucleus genotoxicity assay by laser scanning cytometry

31 March 2020

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In vitro erythropoiesis from bone marrow-derived progenitors provides a physiological assay for toxic and mutagenic compounds

31 March 2020

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Suppression of mutagenic activity of a series of 5HT2c receptor agonists by the incorporation of a gem-dimethyl group: SAR using the Ames test and a DNA unwinding assay

31 March 2020

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Arrhythmogenic mechanisms of non-sedating antihistamines

31 March 2020

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Are hERG channel inhibition and QT interval prolongation all there is in drug-induced torsadogenesis? A review of emerging trends

31 March 2020

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QT-interval prolongation by non-cardiac drugs: lessons to be learned from recent experience

31 March 2020

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Evaluation of functional and binding assays in cells expressing either recombinant or endogenous hERG channel

31 March 2020

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Evaluation of the rubidium efflux assay for preclinical identification of HERG blockade.

31 March 2020

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2-(2-Furanyl)-7-phenyl[1,2,4]triazolo[1,5-c]pyrimidin-5-amine analogs as adenosine A2A antagonists: the successful reduction of hERG activity. Part 2.

31 March 2020

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Optimization of a tertiary alcohol series of phosphodiesterase-4 (PDE4) inhibitors: structure-activity relationship related to PDE4 inhibition and human ether-a-go-go related gene potassium channel binding affinity

31 March 2020

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Predicting in vivo drug interactions from in vitro drug discovery data

31 March 2020

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Calcein accumulation as a fluorometric functional assay of the multidrug transporter

31 March 2020

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The design, preparation and SAR of novel small molecule sodium (Na(+)) channel blockers

31 March 2020

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Design and Synthesis of trans-3-(2-(4-((3-(3-(5-Methyl-1,2,4-oxadiazolyl))- phenyl)carboxamido)cyclohexyl)ethyl)-7-methylsulfonyl-2,3,4,5-tetrahydro- 1H-3-benzazepine (SB-414796): A Potent and Selective Dopamine D3 Receptor Antagonist

31 March 2020

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SAR of 4-hydroxypiperidine and hydroxyalkyl substituted heterocycles as novel p38 map kinase inhibitors

31 March 2020

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Design and synthesis of new templates derived from pyrrolopyrimidine as selective multidrug-resistance-associated protein inhibitors in multidrug resistance

31 March 2020

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Drug metabolites in safety testing

31 March 2020

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An in vitro approach to detect metabolite toxicity due to CYP3A4-dependent bioactivation of xenobiotics

31 March 2020

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Role of metabolism in drug-induced idiosyncratic hepatotoxicity

31 March 2020

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Investigation of toxic metabolites during drug development

31 March 2020

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Drug-protein adducts: an industry perspective on minimizing the potential for drug bioactivation in drug discovery and development

31 March 2020

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Cytochrome P450 3A4-mediated bioactivation of raloxifene: irreversible enzyme inhibition and thiol adduct formation

31 March 2020

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Future of toxicology-metabolic activation and drug design: challenges and opportunities in chemical toxicology

31 March 2020

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Pathogenesis of cardiovascular alterations in dogs treated with minoxidil

31 March 2020

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The pharmacologic basis of the cardiovascular toxicity of minoxidil in the dog

31 March 2020

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Relationship between serum concentrations, hemodynamic effects, and cardiovascular lesions in dogs treated with minoxidil

31 March 2020

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Drug-induced vascular injury--a quest for biomarkers.

31 March 2020

1 reference

Recent update on the PPARα-null mouse

31 March 2020

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Role of Drug Disposition in Drug Hypersensitivity: A Chemical, Molecular, and Clinical Perspective

31 March 2020

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Adverse drug reactions: definitions, diagnosis, and management

31 March 2020

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Inflammation and drug idiosyncrasy--is there a connection?

31 March 2020

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Microarray analysis of lipopolysaccharide potentiation of trovafloxacin-induced liver injury in rats suggests a role for proinflammatory chemokines and neutrophils

31 March 2020

1 reference

Prediction of rodent nongenotoxic carcinogenesis: evaluation of biochemical and tissue changes in rodents following exposure to nine nongenotoxic NTP carcinogens

31 March 2020

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Acute molecular markers of rodent hepatic carcinogenesis identified by transcription profiling

31 March 2020

1 reference

Mode of action: angiotensin-converting enzyme inhibition--developmental effects associated with exposure to ACE inhibitors

31 March 2020

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Placental alterations, intrauterine growth retardation and teratogenicity associated with enalapril use in pregnant rats

31 March 2020

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Platelet inhibitory activity and pharmacokinetics of prasugrel (CS-747) a novel thienopyridine P2Y12 inhibitor: a multiple-dose study in healthy humans

31 March 2020

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Safety and efficacy of aspirin, clopidogrel, and warfarin after coronary stent placement in patients with an indication for anticoagulation

31 March 2020

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Arterial antithrombotic effects of aspirin, heparin, enoxaparin and clopidogrel alone, or in combination, in the rat

31 March 2020

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The in vivo pharmacological profile of CS-747, a novel antiplatelet agent with platelet ADP receptor antagonist properties

31 March 2020

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Antithrombotic effects and bleeding time of thrombin inhibitors and warfarin in the rat

31 March 2020

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Low-molecular-weight heparin (fragmin) and thrombin active-site inhibitor (argatroban) compared in experimental arterial and venous thrombosis and bleeding time

31 March 2020

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Valvular heart disease associated with fenfluramine-phentermine

31 March 2020

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Serotonin 5-ht2c receptor agonists: potential for the treatment of obesity

31 March 2020

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The potential use of selective 5-HT2C agonists in treating obesity

31 March 2020

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Gastrointestinal toxicity with celecoxib vs nonsteroidal anti-inflammatory drugs for osteoarthritis and rheumatoid arthritis: the CLASS study: A randomized controlled trial. Celecoxib Long-term Arthritis Safety Study

31 March 2020

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Comparison of upper gastrointestinal toxicity of rofecoxib and naproxen in patients with rheumatoid arthritis. VIGOR Study Group

31 March 2020

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Drug-induced phospholipidosis: issues and future directions

31 March 2020

1 reference

Aryl acetylenes as mechanism-based inhibitors of cytochrome P450-dependent monooxygenase enzymes

31 March 2020

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Suicide inactivation of cytochrome P450 by midchain and terminal acetylenes. A mechanistic study of inactivation of a plant lauric acid omega-hydroxylase

31 March 2020

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Mechanism-based inhibition of cytochrome P450 3A4 by therapeutic drugs.

31 March 2020

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Polycyclic aromatic hydrocarbons physically intercalate into duplex regions of denatured DNA.

31 March 2020

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Utilization of operational schemes for analog synthesis in drug design

31 March 2020

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Broad-spectrum matrix metalloproteinase inhibitor marimastat-induced musculoskeletal side effects in rats

31 March 2020

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Differential display in rat livers treated for 13 weeks with phenobarbital implicates a role for metabolic and oxidative stress in nongenotoxic carcinogenicity

31 March 2020

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Identification of putative gene based markers of renal toxicity

31 March 2020

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Animal models of arthritis: relevance to human disease

31 March 2020

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Animal models of emphysema and their relevance to studies of particle-induced disease

31 March 2020

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Animal models of chronic bronchitis and their relevance to studies of particle-induced disease

31 March 2020

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Structural, functional, and molecular characterization of the SHHF model of heart failure

31 March 2020

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Effects of concurrent ozone exposure on the pathogenesis of cigarette smoke-induced emphysema in B6C3F1 mice

31 March 2020

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Non-invasive MRI of mouse models of atherosclerosis

31 March 2020

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Pioglitazone inhibits in-stent restenosis in atherosclerotic rabbits by targeting transforming growth factor-beta and MCP-1.

31 March 2020

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MDOC and atorvastatin have potential antiinflammatory effects in vascular endothelium of apoE-/- mouse model of atherosclerosis

31 March 2020

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Immunohistochemical analysis of Clara cell secretory protein expression in a transgenic model of mouse lung carcinogenesis

31 March 2020

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Selective cyclooxygenase-2 inhibition does not affect the healing of cutaneous full-thickness incisional wounds in SKH-1 mice

31 March 2020

1 reference

Aldosterone/salt induces renal inflammation and fibrosis in hypertensive rats

31 March 2020

1 reference

Interspecies differences in renal localization of cyclooxygenase isoforms: implications in nonsteroidal antiinflammatory drug-related nephrotoxicity

31 March 2020

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Interspecies differences in the nephrotoxic response to cyclooxygenase inhibition

31 March 2020

1 reference

Combinatorial biomarkers: From early toxicology assays to patient population profiling

31 March 2020

1 reference

Molecular approaches to the identification of biomarkers of exposure and effect--report of an expert meeting organized by COST Action B15. November 28, 2003.

31 March 2020

1 reference

Prediction of nephrotoxicant action and identification of candidate toxicity-related biomarkers.

31 March 2020

1 reference

Toxicoproteomics: serum proteomic pattern diagnostics for early detection of drug induced cardiac toxicities and cardioprotection

31 March 2020

1 reference

Adipsin, a biomarker of gastrointestinal toxicity mediated by a functional gamma-secretase inhibitor

31 March 2020

1 reference

Peroxisome proliferation and nongenotoxic carcinogenesis: commentary on a symposium

31 March 2020

1 reference

Peroxisome proliferator-activated receptor-alpha and the pleiotropic responses to peroxisome proliferators

31 March 2020

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The peroxisome proliferator (PP) response element upstream of the human acyl CoA oxidase gene is inactive among a sample human population: significance for species differences in response to PPs.

31 March 2020

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Do peroxisome proliferating compounds pose a hepatocarcinogenic hazard to humans?

31 March 2020

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Studies on the mode of action for thyroid gland tumor promotion in rats by phenobarbital

31 March 2020

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Thyroid gland neoplasia: non-genotoxic mechanisms

31 March 2020

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Use and application of stem cells in toxicology

31 March 2020

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The role of investigative molecular toxicology in early stage drug development

31 March 2020

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Application of proteomic technologies in the drug development process

31 March 2020

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Metabonomics: its potential as a tool in toxicology for safety assessment and data integration

31 March 2020

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Systems toxicology: applications of toxicogenomics, transcriptomics, proteomics and metabolomics in toxicology

31 March 2020

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Toxicogenomics and drug discovery: will new technologies help us produce better drugs?

31 March 2020

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Toxicogenomics: an opportunity to optimise drug development and safety evaluation

31 March 2020

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Revolution through genomics in investigative and discovery toxicology

31 March 2020

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Critical role for sphingosine kinase-1 in regulating survival of neuroblastoma cells exposed to amyloid-beta peptide

31 March 2020

1 reference

Xpa and Xpa/p53+/- knockout mice: overview of available data

31 March 2020

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The Tg.AC (v-Ha-ras) transgenic mouse: nature of the model

31 March 2020

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P53+/- hemizygous knockout mouse: overview of available data

31 March 2020

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Humanized beta-thalassemia mouse model containing the common IVSI-110 splicing mutation

31 March 2020

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Nile Red binding to HepG2 cells: an improved assay for in vitro studies of hepatosteatosis

31 March 2020

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Analysis of two matrix metalloproteinase inhibitors and their metabolites for induction of phospholipidosis in rat and human hepatocytes(1).

31 March 2020

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Validation of an in vitro screen for phospholipidosis using a high-content biology platform

31 March 2020

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Apoptotic photoreceptor cell death in mouse models of retinitis pigmentosa

31 March 2020

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A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V

31 March 2020

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Fluorometric and Colorimetric Detection of Caspase Activity Associated with Apoptosis

31 March 2020

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A quantitative fluorimetric assay for the determination of oxidant production by polymorphonuclear leukocytes: Its use in the simultaneous fluorimetric assay of cellular activation processes

31 March 2020

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Immunological approaches to the characterization and diagnosis of mitochondrial disease

31 March 2020

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Inhibition of microsomal triglyceride transfer protein: another mechanism for drug-induced steatosis in mice.

31 March 2020

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Synthesis and SAR of 5-amino- and 5-(aminomethyl)benzofuran histamine H3 receptor antagonists with improved potency

31 March 2020

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Endogenous glucocorticoids regulate an inducible cyclooxygenase enzyme

31 March 2020

1 reference

The 45-year story of the development of an anti-aldosterone more specific than spironolactone

31 March 2020

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Pharmacokinetics and pharmacodynamics of mineralocorticoid blocking agents and their effects on potassium homeostasis

31 March 2020

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The protein kinase complement of the human genome

31 March 2020

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A qualitative assessment of developmental toxicity within a series of structurally related dopamine mimetics

31 March 2020

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Inhibitor focusing: direct selection of drug targets from proteomes using activity-based probes.

31 March 2020

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Pharmacologic options for aggressive low-density lipoprotein cholesterol lowering: benefits versus risks

31 March 2020

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Pharmacological interactions of statins.

31 March 2020

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Effects of HMG-CoA reductase inhibitors on skeletal muscle: are all statins the same?

31 March 2020

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HMG-CoA reductase inhibitors and myotoxicity

31 March 2020

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Knockouts model the 100 best-selling drugs--will they model the next 100?

31 March 2020

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31 March 2020

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Cardiovascular effects after inhalation of large doses of albuterol dry powder in rats, monkeys, and dogs: a species comparison

31 March 2020

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Prospects for reducing and refining the use of dogs in the regulatory toxicity testing of pharmaceuticals

31 March 2020

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Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings

31 March 2020

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Drug-induced phospholipidosis: are there functional consequences?

31 March 2020

1 reference

inferred from DOI database lookup

7 January 2021

based on heuristic

The comet assay: a comprehensive review

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inferred from DOI database lookup

7 January 2021

based on heuristic

Identifiers

DOI

10.1038/NRD2378

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16 August 2017

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