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

Data up to Jan 2025

Published2007
Citations346
References163

Total Citations Per Year

Abstract

References (163)

Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings 1PII of original article: S0169-409X(96)00423-1. The article was originally published in Advanced Drug Delivery Reviews 23 (1997) 3–25. 1

2001 • 16,438 citations

The Protein Kinase Complement of the Human Genome

2002 • 7,708 citations

Methods for detecting carcinogens and mutagens with the salmonella/mammalian-microsome mutagenicity test

1975 • 7,413 citations

Revised methods for the Salmonella mutagenicity test

1983 • 7,295 citations

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

1995 • 5,208 citations

The price of innovation: new estimates of drug development costs

2003 • 4,276 citations

Comparison of Upper Gastrointestinal Toxicity of Rofecoxib and Naproxen in Patients with Rheumatoid Arthritis

2000 • 4,048 citations

Can the pharmaceutical industry reduce attrition rates?

2004 • 3,946 citations

Gastrointestinal Toxicity With Celecoxib vs Nonsteroidal Anti-inflammatory Drugs for Osteoarthritis and Rheumatoid Arthritis

2000 • 3,176 citations

The druggable genome

2002 • 3,099 citations

Adverse drug reactions: definitions, diagnosis, and management

2000 • 2,723 citations

Polycyclic aromatic hydrocarbons physically intercalate into duplex regions of denatured DNA

1987 • 1,942 citations

Concordance of the Toxicity of Pharmaceuticals in Humans and in Animals

2000 • 1,895 citations

The comet assay: a comprehensive review

1995 • 1,690 citations

Valvular Heart Disease Associated with Fenfluramine–Phentermine

1997 • 1,595 citations

Predicting in vivo drug interactions from in vitro drug discovery data

2005 • 842 citations

Prediction of Chemical Carcinogenicity in Rodents from in Vitro Genetic Toxicity Assays

1987 • 818 citations

Evaluation of the ability of a battery of three in vitro genotoxicity tests to discriminate rodent carcinogens and non-carcinogens

2005 • 724 citations

Drug−Protein Adducts: An Industry Perspective on Minimizing the Potential for Drug Bioactivation in Drug Discovery and Development

2003 • 697 citations

Evidence for Possible Involvement of 5-HT 2B Receptors in the Cardiac Valvulopathy Associated With Fenfluramine and Other Serotonergic Medications

2000 • 668 citations

Apoptotic photoreceptor cell death in mouse models of retinitis pigmentosa.

1994 • 630 citations

Near Completely Humanized Liver in Mice Shows Human-Type Metabolic Responses to Drugs

2004 • 528 citations

Aldosterone/salt induces renal inflammation and fibrosis in hypertensive rats

2003 • 517 citations

Mechanism-Based Inhibition of Cytochrome P450 3A4 by Therapeutic Drugs

2005 • 478 citations

Endogenous glucocorticoids regulate an inducible cyclooxygenase enzyme.

1992 • 471 citations

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

1988 • 467 citations

Mutagen testing using TRP+ reversion in Escherichia coli

1976 • 439 citations

Utilization of operational schemes for analog synthesis in drug design

1972 • 435 citations

Possible role of valvular serotonin 5-HT(2B) receptors in the cardiopathy associated with fenfluramine.

2000 • 403 citations

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

2002 • 392 citations

Drug Metabolites in Safety Testing

2002 • 368 citations

Fluorometric and Colorimetric Detection of Caspase Activity Associated with Apoptosis

1997 • 347 citations

Adipsin, a Biomarker of Gastrointestinal Toxicity Mediated by a Functional γ-Secretase Inhibitor

2003 • 343 citations

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

1984 • 322 citations

Role of Metabolism in Drug-Induced Idiosyncratic Hepatotoxicity

2005 • 322 citations

Evaluation of the ability of a battery of three in vitro genotoxicity tests to discriminate rodent carcinogens and non-carcinogens

2008 • 320 citations

Calcein accumulation as a fluorometric functional assay of the multidrug transporter

1994 • 316 citations

Proteomic analysis and identification of new biomarkers and therapeutic targets for invasive ovarian cancer

2002 • 291 citations

Animal Models of Arthritis: Relevance to Human Disease

1999 • 288 citations

Prospects for productivity

2004 • 283 citations

Use and Application of Stem Cells in Toxicology

2004 • 280 citations

HMG-CoA Reductase Inhibitors and Myotoxicity

2000 • 279 citations

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

1998 • 269 citations

The discovery and function of COX-2.

1997 • 268 citations

Drug-Induced Phospholipidosis: Are There Functional Consequences?

2001 • 259 citations

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

2003 • 255 citations

Use of a simplified fluctuation test to detect low levels of mutagens

1976 • 254 citations

Identification of putative gene based markers of renal toxicity.

2004 • 252 citations

The SOS chromotest: a review

1993 • 249 citations

Do Peroxisome Proliferating Compounds Pose a Hepatocarcinogenic Hazard to Humans?

1998 • 248 citations

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

2000 • 237 citations

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

2000 • 235 citations

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

2004 • 233 citations

Drug-induced phospholipidosis: issues and future directions

2006 • 218 citations

Effects of HMG-CoA Reductase Inhibitors on Skeletal Muscle

2002 • 210 citations

Interspecies Differences in Renal Localization of Cyclooxygenase Isoforms: Implications in Nonsteroidal Antiinflammatory Drug-Related Nephrotoxicity

1998 • 205 citations

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

2002 • 187 citations

Pharmaceutical Industry Profile

2005 • 186 citations

Peroxisome proliferation and nongenotoxic carcinogenesis: Commentary on a symposium*1

1991 • 185 citations

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

2004 • 182 citations

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

2003 • 181 citations

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

2005 • 178 citations

Report from working group on in vitro tests for chromosomal aberrations

1994 • 174 citations

Pharmacokinetics and Pharmacodynamics of Mineralocorticoid Blocking Agents and their Effects on Potassium Homeostasis

2005 • 171 citations

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

2003 • 165 citations

Future of ToxicologyMetabolic Activation and Drug Design: Challenges and Opportunities in Chemical Toxicology

2006 • 159 citations

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

2005 • 157 citations

Metabonomics: Its Potential as a Tool in Toxicology for Safety Assessment and Data Integration

2004 • 156 citations

Cytochrome P450 3A4-Mediated Bioactivation of Raloxifene: Irreversible Enzyme Inhibition and Thiol Adduct Formation

2002 • 150 citations

Prediction of Nephrotoxicant Action and Identification of Candidate Toxicity-Related Biomarkers

2005 • 134 citations

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

2004 • 132 citations

Inflammation and Drug Idiosyncrasy—Is There a Connection?

2003 • 130 citations

VITOTOX� bacterial genotoxicity and toxicity test for the rapid screening of chemicals

1999 • 126 citations

Microarray Analysis of Lipopolysaccharide Potentiation of Trovafloxacin-Induced Liver Injury in Rats Suggests a Role for Proinflammatory Chemokines and Neutrophils

2005 • 123 citations

The automated bone marrow micronucleus test

1989 • 121 citations

Antithrombotic Effects and Bleeding Time of Thrombin Inhibitors and Warfarin in the Rat

1999 • 114 citations

The utility of DNA microarrays for characterizing genotoxicity.

2004 • 109 citations

In Vivo Detection of Vascular Adhesion Protein-1 in Experimental Inflammation

2000 • 108 citations

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

1988 • 107 citations

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

2006 • 107 citations

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

2006 • 105 citations

Aryl Acetylenes as Mechanism-Based Inhibitors of Cytochrome P450-Dependent Monooxygenase Enzymes

1997 • 105 citations

p53 +/- Hemizygous Knockout Mouse: Overview of Available Data

2001 • 105 citations

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

2002 • 104 citations

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

1999 • 103 citations

Nile Red Binding to HepG2 Cells: An Improved Assay forIn VitroStudies of Hepatosteatosis

2001 • 103 citations

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

2003 • 97 citations

Recent update on the PPARα-null mouse

1997 • 97 citations

Aberrant Renal Vascular Morphology and Renin Expression in Mutant Mice Lacking Angiotensin-Converting Enzyme

1997 • 97 citations

SEROTONIN 5-HT2C RECEPTOR AGONISTS: POTENTIAL FOR THE TREATMENT OF OBESITY

2005 • 96 citations

Thyroid gland neoplasia: non-genotoxic mechanisms

1992 • 93 citations

Toxicoproteomics: Serum Proteomic Pattern Diagnostics for Early Detection of Drug Induced Cardiac Toxicities and Cardioprotection

2004 • 92 citations

Investigation of toxic metabolites during drug development

2005 • 91 citations

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

2005 • 89 citations

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

2004 • 87 citations

Pharmacological interactions of statins

2002 • 84 citations

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

2003 • 82 citations

Drug-induced vascular injury—a quest for biomarkers

2004 • 81 citations

Oxidative Stress Mediated Idiosyncratic Drug Toxicity

2005 • 80 citations

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

2002 • 80 citations

Application of proteomic technologies in the drug development process

2004 • 80 citations

Pharmacologic Options for Aggressive Low-Density Lipoprotein Cholesterol Lowering: Benefits Versus Risks

2005 • 75 citations

Acute Molecular Markers of Rodent Hepatic Carcinogenesis Identified by Transcription Profiling

2004 • 75 citations

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

2003 • 73 citations

Pioglitazone Inhibits In-Stent Restenosis in Atherosclerotic Rabbits by Targeting Transforming Growth Factor-β and MCP-1

2006 • 73 citations

Arrhythmogenic mechanisms of non‐sedating antihistamines

1999 • 69 citations

Pathogenesis of Cardiovascular Alterations in Dogs Treated with Minoxidil

1989 • 66 citations

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

2003 • 65 citations

Mechanisms and pathogenesis of thyroid cancer in animals and man

1995 • 64 citations

Synthesis and SAR of 5-Amino- and 5-(Aminomethyl)benzofuran Histamine H3 Receptor Antagonists with Improved Potency

2005 • 60 citations

Safety Assessment of Biotechnology-Derived Pharmaceuticals: ICH and Beyond

1999 • 60 citations

The potential use of selective 5-HT2Cagonists in treating obesity

2006 • 58 citations

Critical Role for Sphingosine Kinase-1 in Regulating Survival of Neuroblastoma Cells Exposed to Amyloid-β Peptide

2007 • 57 citations

Analysis of two matrix metalloproteinase inhibitors and their metabolites for induction of phospholipidosis in rat and human hepatocytes11Abbreviations: MMP, matrix metalloproteinase; MMPI, matrix metalloproteinase inhibitor; DMEM, Dulbecco’s modified Eagle’s medium; FBS, fetal bovine serum; NBD-PE, N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)1,2-dihexadecanoyl-sn-glycero-3-phosphoethanolamine; and MTT, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide; DMSO, dimethylsulfoxide; HPLC, high …

2001 • 55 citations

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

2007 • 53 citations

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

2000 • 51 citations

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

2001 • 51 citations

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

2005 • 50 citations

The Tg.AC (v-Ha-ras) Transgenic Mouse: Nature of the Model

2001 • 49 citations

ANIMAL MODELS OF EMPHYSEMA AND THEIR RELEVANCE TO STUDIES OF PARTICLE-INDUCED DISEASE

2000 • 47 citations

Low-Molecular-Weight Heparin (Fragmin) and Thrombin Active-Site Inhibitor (Argatroban) Compared in Experimental Arterial and Venous Thrombosis and Bleeding Time

1996 • 47 citations

ANIMAL MODELS OF CHRONIC BRONCHITIS AND THEIR RELEVANCE TO STUDIES OF PARTICLE-INDUCED DISEASE

2000 • 47 citations

Yeast DEL assay detects clastogens

2005 • 44 citations

Transcription Profiling Distinguishes Dose-Dependent Effects in the Livers of Rats Treated with Clofibrate

2003 • 44 citations

The Pharmacologic Basis of the Cardiovascular Toxicity of Minoxidil in the Dog

1995 • 43 citations

Design and Synthesis of New Templates Derived from Pyrrolopyrimidine as Selective Multidrug-Resistance-Associated Protein Inhibitors in Multidrug Resistance

2004 • 43 citations

Genetically Engineered Animals in Drug Discovery and Development: A Maturing Resource for Toxicologic Research

2004 • 41 citations

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

2005 • 39 citations

Revolution through Genomics in Investigative and Discovery Toxicology

1999 • 39 citations

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

2003 • 36 citations

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

2000 • 36 citations

Humanized β-Thalassemia Mouse Model Containing the Common IVSI-110 Splicing Mutation

2006 • 35 citations

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

2006 • 34 citations

Immunological approaches to the characterization and diagnosis of mitochondrial disease

2004 • 34 citations

Suicide Inactivation of Cytochrome P450 by Midchain and Terminal Acetylenes

1997 • 33 citations

Interspecies Differences in the Nephrotoxic Response to Cyclooxygenase Inhibition

2004 • 33 citations

Automation of mouse micronucleus genotoxicity assay by laser scanning cytometry

2001 • 33 citations

Evaluation of the Rubidium Efflux Assay for Preclinical Identification of hERG Blockade

2006 • 33 citations

Relationship between Serum Concentrations, Hemodynamic Effects, and Cardiovascular Lesions in Dogs Treated with Minoxidil

1996 • 32 citations

Mode of Action: Angiotensin-Converting Enzyme Inhibition—Developmental Effects Associated With Exposure to ACE Inhibitors

2005 • 31 citations

Combinatorial biomarkers: From early toxicology assays to patient population profiling

2005 • 31 citations

Non‐invasive MRI of mouse models of atherosclerosis

2007 • 28 citations

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

2006 • 26 citations

Xpa and Xpa/p53 +/- Knockout Mice: Overview of Available Data

2001 • 25 citations

Toxicogenomics: an opportunity to optimise drug development and safety evaluation

2002 • 24 citations

EFFECTS OF CONCURRENT OZONE EXPOSURE ON THE PATHOGENESIS OF CIGARETTE SMOKE-INDUCED EMPHYSEMA IN B6C3F 1 MICE

2002 • 23 citations

Cardiovascular Effects after Inhalation of Large Doses of Albuterol Dry Powder in Rats, Monkeys, and Dogs: A Species Comparison

1997 • 22 citations

Molecular approaches to the identification of biomarkers of exposure and effect—report of an expert meeting organized by COST Action B15

2005 • 21 citations

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

2005 • 21 citations

Differential Display in Rat Livers Treated for 13 Weeks with Phenobarbital Implicates a Role for Metabolic and Oxidative Stress in Nongenotoxic Carcinogenicity

2005 • 21 citations

Flow cytometric analysis of micronucleated reticulocytes in mouse bone marrow

1997 • 21 citations

DNA vaccines: safety aspect assessment and regulation.

2006 • 21 citations

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

2005 • 20 citations

Mass Spectrometry in Drug Discovery: A Current Review

2004 • 17 citations

A miniaturized Ames mutagenicity assay employing bioluminescent strains of Salmonella typhimurium

1995 • 15 citations

The role of investigative molecular toxicology in early stage drug development

2003 • 14 citations

The Pathologist and Toxicologist in Pharmaceutical Product Discovery

1999 • 13 citations

Inhibitor Focusing: Direct Selection of Drug Targets from Proteomes Using Activity-Based Probes

2003 • 12 citations

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

1998 • 12 citations

Placental Alterations, Intrauterine Growth Retardation and Teratogenicity Associated with Enalapril Use in Pregnant Rats

1992 • 11 citations

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

1992 • 7 citations

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

2004 • 6 citations

Peroxisome Proliferator-Activated Receptor-alpha and the Pleiotropic Responses to Peroxisome Proliferators

1998 • 4 citations

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