The use of histologically defined specific biomarkers in drug development with special reference to the glutathione S-transferases.
Failure of drug candidates late in development is very expensive. This can be reduced by using more specific biomarkers of effect and toxicity during the preclinical and development testing. However, traditional toxicity tests have not been developed to study toxicology and so may lack sufficient sensitivity and specificity hence the search for new biomarkers using the many "-omics" technologies. Important aspects of useful biomarkers are that their origin is known and localised so that one knows what is being observed. Furthermore, biomarkers with a localised origin are less likely to be subject to background variation and have a wider dynamic range. This paper will discuss how using biomarkers with a known cellular origin, toxic effects can be found earlier and at lower doses of compound.
Shaw
Martin
M
Biotrin International, 93 The Rise, Mount Merrion, Co Dublin, Ireland. Martin.shaw@biotrin.ie
D000220:Adaptation, Biological / Q000187:drug effects; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D056486:Chemical and Drug Induced Liver Injury; D015195:Drug Design; D004353:Drug Evaluation, Preclinical / Q000379:methods; D064420:Drug-Related Side Effects and Adverse Reactions / Q000175:diagnosis; D005982:Glutathione Transferase / Q000032:analysis*; D006652:Histological Techniques / Q000379:methods*; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D007668:Kidney / Q000166:cytology / Q000187:drug effects; D007674:Kidney Diseases / Q000139:chemically induced / Q000175:diagnosis; D008099:Liver / Q000166:cytology / Q000187:drug effects; D008107:Liver Diseases / Q000175:diagnosis; D009928:Organ Specificity
D015415:Biomarkers; D005982:Glutathione Transferase