title: How lipidomics provides new insight into drug discovery.
abstract: BACKGROUND
  Automated lipidomic methods based on mass spectrometry (MS) are now proposed to screen a large variety of candidate drugs available that inhibit de novo lipid synthesis and replace tedious methods based on radiotracer incorporation. A major new interest in inhibitors of de novo lipogenesis is their proapoptotic effect observed in cancerous cells.
  
  
  METHODS
  In this review, the authors focus on the screening methods of antilipogenic inhibitors targeting the synthesis of malonylCoA (carbonic anhydrase, acetylCoA carboxylase), palmitylCoA (fatty acid synthase condensing and thioesterase subunits) and monounsaturated fatty acids (Δ9-desaturase). The consequences of inhibition depend on how the pathway deviates above the blockade: accelerated mitochondrial fatty acid oxidation following the decreased malonylCoA level, accumulation of ketone bodies and increased cholesterol synthesis following the increased acetylCoA level. Side effects such as anorexia and skin defects may critically decrease therapeutic indices in the long term. The authors emphasize the need for assessment of toxicity in short-term treatments inducing proapoptotic effects observed in aggressive hormone-dependent malignancies.
  
  
  CONCLUSIONS
  The activity of lipogenesis inhibitors can be recognised in lipid profiles established by a combination of MS-based measurements and multivariate analysis processing hundreds of lipid molecular species. Because the method can be automated, it is suitable for screening large chemical libraries, with particular focus on anticancer activities.
authors.affiliation: Sorbonne Universités - UPMC Univ Paris 06, INSERM ERL , 1157, CNRS UMR 7203 LBM, CHU Saint-Antoine 27 rue de Chaligny, F-75012, Paris , France.
authors.forename: Antonin
authors.initials: A
authors.lastname: Lamaziere
authors.forename: Claude
authors.initials: C
authors.lastname: Wolf
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Quinn
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology; D055808:Drug Discovery; D054872:Fatty Acid Synthesis Inhibitors / Q000494:pharmacology; D006801:Humans; D000960:Hypolipidemic Agents / Q000494:pharmacology; D050356:Lipid Metabolism / Q000187:drug effects; D050155:Lipogenesis / Q000187:drug effects; D009369:Neoplasms / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D002257:Carbonic Anhydrase Inhibitors; D054872:Fatty Acid Synthesis Inhibitors; D000960:Hypolipidemic Agents
keywords: anticancer drug; inhibitors of lipogenesis; obesity; pharmacological screening; toxicology