title: Early drug safety evaluation: biomarkers, signatures, and fingerprints.
abstract: When target organ toxicity arises in animal models during routine drug safety evaluation, it raises several key questions: Is this target organ toxicity related to the pharmacology? What is the mode of action (MOA)? Is the target organ toxicity relevant to humans? Pathology or prior knowledge of the compound class may provide clues on a possible MOA for toxicity. However, if this deductive approach yields no results, the inductive approach offered by new technologies can generate novel research leads. For example, toxicogenomics can generate a gene expression profile of the toxicity that can be compared with reference compounds or with other candidate drugs. Similarly, proteomic analysis of the protein profile at the toxic vs. the efficacious dose can provide clues on MOA for the toxicity and may allow differentiation of the pathways of the toxic response from those required for pharmacological activity.
authors.affiliation: Aventis Pharma, Drug Safety Evaluation, Centre de Recherche de Paris, Paris, France. ruth.roberts@aventis.com
authors.forename: Ruth
authors.initials: R
authors.lastname: Roberts
authors.forename: Kelvin
authors.initials: K
authors.lastname: Cain
authors.forename: Beth
authors.initials: B
authors.lastname: Coyle
authors.forename: Caroline
authors.initials: C
authors.lastname: Freathy
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Leonard
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Gautier
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015415:Biomarkers / Q000032:analysis*; D016172:DNA Fingerprinting / Q000379:methods*; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D004364:Pharmaceutical Preparations / Q000032:analysis
chemical_list: D015415:Biomarkers; D004364:Pharmaceutical Preparations