Application of proteomic technologies in the drug development process.
Proteins are the principal targets of drug discovery. Most large pharmaceutical companies now have a proteomics-oriented biotech or academic partner or have started their own proteomics division. Common applications of proteomics in the drug industry include target identification and validation, identification of efficacy and toxicity biomarkers from readily accessible biological fluids, and investigations into mechanisms of drug action or toxicity. Target identification and validation involves identifying proteins whose expression levels or activities change in disease states. These proteins may serve as potential therapeutic targets or may be used to classify patients for clinical trials. Proteomics technologies may also help identify protein-protein interactions that influence either the disease state or the proposed therapy. Efficacy biomarkers are used to assess whether target modulation has occurred. They are used for the characterization of disease models and to assess the effects and mechanism of action of lead candidates in animal models. Toxicity (safety) biomarkers are used to screen compounds in pre-clinical studies for target organ toxicities as well as later on in development during clinical trials. Complementary approaches such as metabolomics and genomics can be used in conjunction with proteomics throughout the drug development process to create more of a unified, systems biology approach.
Walgren
Jennie L
JL
Worldwide Safety Sciences, Pfizer, Inc., 700 Chesterfield Parkway West, Chesterfield, MO 63017, USA.
Thompson
David C
DC
D000818:Animals; D015415:Biomarkers; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D064420:Drug-Related Side Effects and Adverse Reactions; D006801:Humans; D010600:Pharmacology / Q000639:trends*; D011506:Proteins / Q000187:drug effects / Q000235:genetics; D040901:Proteomics / Q000639:trends*
D015415:Biomarkers; D011506:Proteins