title: VeloceGenomics: an accelerated in vivo drug discovery approach to rapidly predict the biologic, drug-like activity of compounds, proteins, or genes.
abstract: OBJECTIVE
  The aim of this study is to test the predictive power of in vivo multiorgan RNA expression profiling in identifying the biologic activity of molecules.
  
  
  METHODS
  Animals were treated with compound A or B. At the end of the treatment period, in vivo multiorgan microarray-based gene expression data were collected. Investigators masked to the identity of the compounds analyzed the transcriptome signatures to define the molecular pathways affected by treatment and to hypothesize the biologic activity and potential therapeutic indications of the blinded compounds.
  
  
  RESULTS
  For compound A, G-protein-coupled receptors and factors associated with cell growth were affected-growth hormone/insulin-like growth factor-1, glucagon/insulin axes, and general somatomedin-like activity. Deblinding showed the compound to be a somatostatin analog, SOM230, confirming the accuracy of the predicted biologic activity. For compound B, components of the inflammatory cascade potentially mediated by lipopolysaccharide, tumor necrosis factor, or proinflammatory cytokines were affected. The gene expression signatures were most consistent with an interleukin-6 family activity. Deblinding revealed that compound B was leukemia inhibitory factor.
  
  
  CONCLUSIONS
  VeloceGenomics is a strategy of coupling in vivo compound testing with genomic technologies. The process enables prediction of the mechanism of action and, coupled with other relevant data, prediction of the suitability of compounds for advancement in the drug development process.
authors.affiliation: Department of Exploratory Development, Biomarker Development, Novartis Pharma A.G., Postfach, 4002, Basel, Switzerland.
authors.forename: Ruben
authors.initials: R
authors.lastname: Papoian
authors.forename: Andreas
authors.initials: A
authors.lastname: Scherer
authors.forename: Muriel
authors.initials: M
authors.lastname: Saulnier
authors.forename: Frank
authors.initials: F
authors.lastname: Staedtler
authors.forename: André
authors.initials: A
authors.lastname: Cordier
authors.forename: Francois
authors.initials: F
authors.lastname: Legay
authors.forename: Gerard
authors.initials: G
authors.lastname: Maurer
authors.forename: Joerg
authors.initials: J
authors.lastname: Staeheli
authors.forename: Jacky
authors.initials: J
authors.lastname: Vonderscher
authors.forename: Salah-Dine
authors.initials: SD
authors.lastname: Chibout
mesh_terms: D000818:Animals; D015195:Drug Design; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D015850:Interleukin-6 / Q000494:pharmacology; D053605:Leukemia Inhibitory Factor; D008252:Macaca fascicularis; D008297:Male; D010597:Pharmacogenetics / Q000379:methods*; D011237:Predictive Value of Tests; D040081:Protein Array Analysis; D011506:Proteins / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013004:Somatostatin / Q000031:analogs & derivatives / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D011506:Proteins; D012333:RNA, Messenger; D013004:Somatostatin; C517782:pasireotide