Development of a Medium-Throughput Targeted LCMS Assay to Detect Endogenous Cellular Levels of Malonyl-CoA to Screen Fatty Acid Synthase Inhibitors

Journal of Biomolecular Screening

Volumn 21, Issue 2, 2016, Pages 111-116

  Hopcroft, Philip J ^a   Fisher, David I ^a  

^a ASTRAZENECA   (United Kingdom)

Author keywords

fatty acid synthase; LCMS; malonyl CoA; screening

Indexed keywords

FATTY ACID SYNTHASE INHIBITOR; MALONYL COENZYME A; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE; ENZYME INHIBITOR; FATTY ACID; FATTY ACID SYNTHASE; NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE;

ARTICLE; CELL LEVEL; CELL SCREENING; CONTROLLED STUDY; DOSE RESPONSE; EC50; FATTY ACID SYNTHESIS; HUMAN; HUMAN CELL; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; MODULATION; PRIORITY JOURNAL; REPRODUCIBILITY; STRUCTURE ACTIVITY RELATION; ANTAGONISTS AND INHIBITORS; BIOASSAY; CHEMISTRY; ENZYME SPECIFICITY; PROCEDURES; TUMOR CELL LINE;

BIOLOGICAL ASSAY; CELL LINE, TUMOR; CHROMATOGRAPHY, LIQUID; ENZYME INHIBITORS; FATTY ACID SYNTHASES; FATTY ACIDS; HUMANS; MALONYL COENZYME A; MASS SPECTROMETRY; NADP; STRUCTURE-ACTIVITY RELATIONSHIP; SUBSTRATE SPECIFICITY;

EID: 84954565247     PISSN: 10870571     EISSN: 1552454X     Source Type: Journal    
DOI: 10.1177/1087057115617894     Document Type: Article

References (15)

1. Wakil S. J., Fatty Acid Synthase, a Proficient Multifunctional Enzyme. Biochemistry 1989, 28, 4523-4530.
2. Cabarcas S. M., Hurt E. M., Farrar W. L., Defining the Molecular Nexus of Cancer, Type 2 Diabetes and Cardiovascular Disease. Curr. Mol. Med. 2010, 10, 744-755.
3. Knobloch M., Braun S. M., Zurkirchen L., et al. Metabolic Control of Adult Neural Stem Cell Activity by Fasn-Dependent Lipogenesis. Nature 2013, 493, 226-230.
4. Kuhajda F. P., Fatty-Acid Synthase and Human Cancer: New Perspectives on Its Role in Tumor Biology. Nutrition 2000, 16, 202-208.
5. Visca P., Sebastiani V., Botti C., et al. Fatty Acid Synthase (FAS) Is a Marker of Increased Risk of Recurrence in Lung Carcinoma. Anticancer Res. 2004, 24, 4169-4173.
6. Hopperton K. E., Duncan R. E., Bazinet R. P., et al. Fatty Acid Synthase Plays a Role in Cancer Metabolism Beyond Providing Fatty Acids for Phospholipid Synthesis or Sustaining Elevations in Glycolytic Activity. Exp. Cell Res. 2014, 320, 302-310.
7. Sadowski M. C., Pouwer R. H., Gunter J. H., et al. The Fatty Acid Synthase Inhibitor Triclosan: Repurposing an Anti-Microbial Agent for Targeting Prostate Cancer. Oncotarget 2014, 5, 9362-9381.
8. Carvalho M. A., Zecchin K. G., Seguin F., et al. Fatty Acid Synthase Inhibition with Orlistat Promotes Apoptosis and Reduces Cell Growth and Lymph Node Metastasis in a Mouse Melanoma Model. Int. J. Cancer 2008, 123, 2557-2565.
9. Pizer E. S., Thupari J., Han W. F., et al. Malonyl-Coenzyme-A Is a Potential Mediator of Cytotoxicity Induced by Fatty-Acid Synthase Inhibition in Human Breast Cancer Cells and Xenografts. Cancer Res. 2000, 60, 213-218.
10. Thupari J. N., Pinn M. L., Kuhajda F. P., Fatty Acid Synthase Inhibition in Human Breast Cancer Cells Leads to Malonyl-CoA-Induced Inhibition of Fatty Acid Oxidation and Cytotoxicity. Biochem. Biophys. Res. Commun. 2001, 285, 217-223.
11. Kridel S. J., Axelrod F., Rozenkrantz N., et al. Orlistat Is a Novel Inhibitor of Fatty Acid Synthase with Antitumor Activity. Cancer Res. 2004, 64, 2070-2075.
12. Browne C. D., Hindmarsh E. J., Smith J. W., Inhibition of Endothelial Cell Proliferation and Angiogenesis by Orlistat, a Fatty Acid Synthase Inhibitor. FASEB J. 2006, 20, 2027-2035.
13. Gilibili R. R., Kandaswamy M., Sharma K., et al. Development and Validation of a Highly Sensitive LC-MS/MS Method for Simultaneous Quantitation of Acetyl-CoA and Malonyl-CoA in Animal Tissues. Biomed. Chromatogr. 2011, 25, 1352-1359.
14. Onorato J. M., Chen L., Shipkova P., et al. Liquid-Liquid Extraction Coupled with LC/MS/MS for Monitoring of Malonyl-CoA in Rat Brain Tissue. Anal. Bioanal. Chem. 2010, 397, 3137-3142.
15. Knowles L. M., Axelrod F., Browne C. D., et al. A Fatty Acid Synthase Blockade Induces Tumor Cell-Cycle Arrest by Down-Regulating Skp2. J. Biol. Chem. 2004, 279, 30540-30545.