Identification of end points relevant to detection of potentially adverse drug reactions.
Expectations are high that the use of proteomics, gene arrays and metabonomics will improve risk assessment and enable prediction of toxicity early in drug development. These molecular profiling techniques may be used to classify compounds and to identify predictive markers that can be used to screen large numbers of chemicals. One of the challenges for the scientific community is to discriminate between changes in gene/protein expression and metabolic profiles reflecting physiological/adaptive responses, and changes related to pathology and toxicology. In these proceedings we provide a brief overview of the technologies with focus on proteomics and the possible applications to mechanistic and predictive toxicology. The discussion also includes strengths and limitations of molecular profiling technologies.
Hellmold
Heike
H
AstraZeneca R&D Södertälje, Molecular Toxicology, Safety Assessment B681, 15185, Sweden. heike.hellmold@astrazeneca.com
Nilsson
Charlotte B
CB
Schuppe-Koistinen
Ina
I
Kenne
Kerstin
K
Wärngård
Lars
L
D000818:Animals; D064420:Drug-Related Side Effects and Adverse Reactions; D015180:Electrophoresis, Gel, Two-Dimensional; D004591:Electrophoresis, Polyacrylamide Gel; D023381:Endpoint Determination; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D013058:Mass Spectrometry / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D020543:Proteome / Q000032:analysis / Q000187:drug effects*; D014116:Toxicology / Q000379:methods* / Q000639:trends
D020543:Proteome