Research Topics
| Dominic P WilliamsSummaryAffiliation: University of Liverpool Country: UK Publications
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Detail Information
Publications
The role of metabolic activation in drug-induced hepatotoxicityB Kevin Park
Department of Pharmacology and Therapeutics, University of Liverpool, Sherrington Buildings, Liverpool, Merseyside L69 3GE, United Kingdom
Annu Rev Pharmacol Toxicol 45:177-202. 2005....- Toxicophores: groups and metabolic routes associated with increased safety riskDominic P Williams
University of Liverpool, Drug Safety Research Group, Department of Pharmacology and Therapeutics, Liverpool, L69 3GE, UK
Curr Opin Drug Discov Devel 5:104-15. 2002.... - The metabolism and toxicity of furosemide in the Wistar rat and CD-1 mouse: a chemical and biochemical definition of the toxicophoreDominic P Williams
Drug Safety Research Group, Department of Pharmacology and Therapeutics, University of Liverpool, Sherrington Buildings, Ashton Street, Liverpool, Merseyside L69 3GE, UK
J Pharmacol Exp Ther 322:1208-20. 2007..03 and 0.21 +/- 0.1 nmol equivalent bound/mg protein, respectively. Furan rings are part of new chemical entities, and mechanisms underlying species differences in toxicity are important to understand to decrease the drug attrition rate... - Toxicophores: investigations in drug safetyDominic P Williams
Drug Safety Research Group, Department of Pharmacology and Therapeutics, University of Liverpool, Sherrington Building, Ashton Street, L69 3GE, United Kingdom
Toxicology 226:1-11. 2006..More importantly, to understand and manipulate these signalling processes will aid in the design of safer therapeutic agents, but also contribute to the clinical management of liver disease... - Time course toxicogenomic profiles in CD-1 mice after nontoxic and nonlethal hepatotoxic paracetamol administrationD P Williams
Department of Pharmacology and Therapeutics, University of Liverpool, Sherrington Building, Ashton Street, P O Box 147, Liverpool, Merseyside L69 3GE, United Kingdom
Chem Res Toxicol 17:1551-61. 2004..The complete data set can be viewed at http://www.ebi.ac.uk/arrayexpress/. The accession number is E-MEXP-82... - Bioactivation of clozapine by murine cardiac tissue in vivo and in vitroDominic P Williams
Department of Pharmacology and Therapeutics, The University of Liverpool, Liverpool, United Kingdom
Chem Res Toxicol 16:1359-64. 2003..5 +/- 0.06%, respectively. These data indicate that clozapine undergoes bioactivation in the heart to a chemically reactive nitrenium metabolite that may be important in the pathogenesis of myocarditis and cardiomyopathy observed in man... - Idiosyncratic toxicity: the role of toxicophores and bioactivationDominic P Williams
Drug Safety Research Group, Department of Pharmacology and Therapeutics, The University of Liverpool, Liverpool, UK L69 3GE
Drug Discov Today 8:1044-50. 2003..Importantly, the identification of drug-thiol conjugation should provide a warning of potential problems, yet not hinder the development of a potentially therapeutically useful drug... - Functional and toxicological consequences of metabolic bioactivation of methapyrilene via thiophene S-oxidation: Induction of cell defence, apoptosis and hepatic necrosisAmy E Mercer
MRC Centre for Drug Safety Science, Department of Pharmacology and Therapeutics, The University of Liverpool, Sherrington Buildings, Ashton Street, Liverpool L69 3GE, UK
Toxicol Appl Pharmacol 239:297-305. 2009.... - Quantifying the metabolic activation of nevirapine in patients by integrated applications of NMR and mass spectrometriesAbhishek Srivastava
MRC Centre for Drug Safety Science, Department of Pharmacology and Therapeutics, School of Biomedical Sciences, The University of Liverpool, Liverpool, United Kingdom
Drug Metab Dispos 38:122-32. 2010..The method can be used as a template for comparative estimations of bioactivation of any drug in patients... - Investigation of the effect of a panel of model hepatotoxins on the Nrf2-Keap1 defence response pathway in CD-1 miceLaura E Randle
Drug Safety Research Group, Department of Pharmacology and Therapeutics, The University of Liverpool, Sherrington Buildings, Ashton Street, Liverpool L69 3GE, United Kingdom
Toxicology 243:249-60. 2008..However, this was associated with modest changes in hepatic GSH, a delayed development of toxicity and was insufficient to activate an early functional adaptive response to these hepatotoxins... - High-mobility group box-1 protein and keratin-18, circulating serum proteins informative of acetaminophen-induced necrosis and apoptosis in vivoDaniel J Antoine
MRC Centre for Drug Safety Science, Department of Pharmacology and Therapeutics, University of Liverpool, Sherrington Buildings, Ashton Street, Liverpool L693GE, UK
Toxicol Sci 112:521-31. 2009..Based on these findings, potential exists for the qualification and measurement of these proteins to further assist in vitro, in vivo, and clinical bridging in toxicological research... - Identification of the thiophene ring of methapyrilene as a novel bioactivation-dependent hepatic toxicophoreEmma E Graham
Department of Pharmacology and Therapeutics, The University of Liverpool, Liverpool, United Kingdom
J Pharmacol Exp Ther 326:657-71. 2008..Hepatotoxicity in rats was diminished by predosing with 1-aminobenzotriazole. For the first time, a thiophene ring substituent is identified as a bioactivation-dependent toxicophore in hepatocytes... - Acyl glucuronides: the good, the bad and the uglySophie L Regan
MRC Centre for Drug Safety Science, Institute of Translational Medicine, The University of Liverpool, Liverpool L69 3GE, UK
Biopharm Drug Dispos 31:367-95. 2010..Further investigation is required to ascertain whether acyl glucuronide clearance is sufficient to prevent covalent modification of endogenous proteins and consequentially a potential immunological response... - Diet restriction inhibits apoptosis and HMGB1 oxidation and promotes inflammatory cell recruitment during acetaminophen hepatotoxicityDaniel James Antoine
Medical Research Council Centre for Drug Safety Science Department of Pharmacology and Therapeutics, Institute for Translational Medicine, University of Liverpool, Liverpool, UK
Mol Med 16:479-90. 2010..Thus, the inhibition of caspase-driven apoptosis and HMGB1 oxidation by ATP depletion from fasting promotes an inflammatory response during drug-induced hepatotoxicity/liver pathology... - Understanding the role of reactive metabolites in drug-induced hepatotoxicity: state of the scienceDaniel J Antoine
University of Liverpool, MRC Centre for Drug Safety Science, Department of Pharmacology and Therapeutics, L69 3GE, UK
Expert Opin Drug Metab Toxicol 4:1415-27. 2008..Some of the steps being made to generate improved physiological systems to identify more sensitive, reflective mechanism-based biomarkers to aid the earlier identification of DILI and develop safer medicines are also discussed... - Selection of new chemical entities with decreased potential for adverse drug reactionsKevin B Park
Drug Safety Research Group, Department Pharmacology and Therapeutics, University of Liverpool, Sherrington Building, Ashton St, L69 3GE, United Kingdom
Eur J Pharmacol 549:1-8. 2006..Alternatively, protein modification may induce signalling systems which initiate cell death, an immune response or to an altered tissue genotype... - Development of a transactivator in hepatoma cells that allows expression of phase I, phase II, and chemical defense genesChris E P Goldring
Dept of Pharmacology and Therapeutics, Univ of Liverpool, Sherrington Bldgs, Ashton St, Liverpool, L69 3GE, Merseyside, UK
Am J Physiol Cell Physiol 290:C104-15. 2006..Importantly, doxycycline did not cause obvious changes in the cellular proteome. In conclusion, we have generated hepatocyte-derived cell lines in which expression of genes is fully controllable... - Investigation of toxic metabolites during drug developmentKevin Park
Department of Pharmacology and Therapeutics, Drug Safety Research Group, University of Liverpool, Sherrington Buildings, Liverpool, Merseyside L69 3GE, UK
Toxicol Appl Pharmacol 207:425-34. 2005..This will provide a deeper understanding of potential toxicophores for drug design and define candidate genes for pharmacogenomic approaches to individualized medicines... - Activation of hepatic Nrf2 in vivo by acetaminophen in CD-1 miceChristopher E P Goldring
Department of Pharmacology and Therapeutics, University of Liverpool, Liverpool, Merseyside, UK
Hepatology 39:1267-76. 2004..In conclusion, GSH depletion alone is insufficient for Nrf2 activation: a more direct interaction is required, possibly involving chemical modification of Nrf2 or Keap1, which is facilitated by the prior loss of GSH... - Acridinediones: selective and potent inhibitors of the malaria parasite mitochondrial bc1 complexGiancarlo A Biagini
Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, UK
Mol Pharmacol 73:1347-55. 2008..falciparum bc(1) Q(o). Dihydroacridinediones represent an entirely new class of bc(1) inhibitors and the potential of these compounds as novel antimalarial drugs is discussed... - Molecular forms of HMGB1 and keratin-18 as mechanistic biomarkers for mode of cell death and prognosis during clinical acetaminophen hepatotoxicityDaniel J Antoine
MRC Centre for Drug Safety Science, Department of Molecular and Clinical Pharmacology, University of Liverpool, Liverpool, UK
J Hepatol 56:1070-9. 2012..The study aim was to assess their mechanistic utility to establish the balance between apoptosis, necrosis, and immune cell activation throughout the time course of clinical APAP hepatotoxicity... - Measurement of CD4+ and CD8+ T-lymphocyte cytokine secretion and gene expression changes in p-phenylenediamine allergic patients and tolerant individualsEve M Coulter
Department of Pharmacology, MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, UK
J Invest Dermatol 130:161-74. 2010..These studies show increased activity of Th2 cytokines in CD4+ and CD8+ T cells from individuals with allergic contact dermatitis... - Antimalarial and antitumor evaluation of novel C-10 non-acetal dimers of 10beta-(2-hydroxyethyl)deoxoartemisininJ Prince Jeyadevan
Department of Chemistry, The Robert Robinson Laboratories, University of Liverpool, Liverpool L69 7ZD, UK
J Med Chem 47:1290-8. 2004..This observation emphasizes the importance of two trioxane units for high antiproliferative activity, and we propose that the nature of the linker in dimers of this type plays a crucial role in imparting potent anticancer activity... - Synergistic interactions between commonly used food additives in a developmental neurotoxicity testKaren Lau
Developmental Toxicopathology Unit, Department of Human Anatomy and Cell Biology, University of Liverpool, Sherrington Buildings, Liverpool L69 3GE, UK
Toxicol Sci 90:178-87. 2006..These data have implications for the cellular effects of common chemical entities ingested individually and in combination...