title: Technological advances and proteomic applications in drug discovery and target deconvolution: identification of the pleiotropic effects of statins.
abstract: Proteomic-based techniques provide a powerful tool for identifying the full spectrum of protein targets of a drug, elucidating its mechanism(s) of action, and identifying biomarkers of its efficacy and safety. Herein, we outline the technological advancements in the field, and illustrate the contribution of proteomics to the definition of the pharmacological profile of statins, which represent the cornerstone of the prevention and treatment of cardiovascular diseases (CVDs). Statins act by inhibiting 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase, thus reducing cholesterol biosynthesis and consequently enhancing the clearance of low-density lipoproteins from the blood; however, HMG-CoA reductase inhibition can result in a multitude of additional effects beyond lipid lowering, known as 'pleiotropic effects'. The case of statins highlights the unique contribution of proteomics to the target profiling of a drug molecule.
authors.affiliation: Centro Cardiologico Monzino, IRCCS, Milano, Italy. Electronic address: cristina.banfi@ccfm.it.
authors.forename: Cristina
authors.initials: C
authors.lastname: Banfi
authors.affiliation: Centro Cardiologico Monzino, IRCCS, Milano, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Baetta
authors.affiliation: Centro Cardiologico Monzino, IRCCS, Milano, Italy.
authors.forename: Erica
authors.initials: E
authors.lastname: Gianazza
authors.affiliation: Centro Cardiologico Monzino, IRCCS, Milano, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Tremoli
mesh_terms: D000818:Animals; D015415:Biomarkers; D055808:Drug Discovery; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D058990:Molecular Targeted Therapy; D040901:Proteomics; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors