Identification and characterization of small compound inhibitors of human FATP2.

Biochemical Pharmacology
Angel SandovalConcetta C DiRusso

Abstract

Fatty acid transport proteins (FATPs) are bifunctional proteins, which transport long chain fatty acids into cells and activate very long chain fatty acids by esterification with coenzyme A. In an effort to understand the linkage between cellular fatty acid transport and the pathology associated with excessive accumulation of exogenous fatty acids, we targeted FATP-mediated fatty acid transport in a high throughput screen of more than 100,000 small diverse chemical compounds in yeast expressing human FATP2 (hsFATP2). Compounds were selected for their ability to depress the transport of the fluorescent long chain fatty acid analogue, C(1)-BODIPY-C(12). Among 234 hits identified in the primary screen, 5 compounds, each representative of a structural class, were further characterized in the human Caco-2 and HepG2 cell lines, each of which normally expresses FATP2, and in 3T3-L1 adipocytes, which do not. These compounds were effective in inhibiting uptake with IC(50)s in the low micromolar range in both Caco-2 and HepG2 cells. Inhibition of transport was highly specific for fatty acids and there were no effects of these compounds on cell viability, trans-epithelial electrical resistance, glucose transport, or long chain acyl-CoA sy...Continue Reading

References

Jul 1, 1977·Journal of the National Cancer Institute·J FoghT Orfeo
Sep 1, 1990·Pharmaceutical Research·A R HilgersP S Burton
Sep 1, 1984·The American Journal of Physiology·E GrassetJ F Desjeux
Apr 25, 1997·The Journal of Biological Chemistry·G A Stafford, R H Morse
Jul 6, 2000·European Journal of Biochemistry·C C DirussoP N Black
Jul 4, 2003·Current Opinion in Lipidology·Jean E Schaffer
Feb 1, 1956·The Journal of Clinical Investigation·V P DOLE
Dec 8, 2004·Analytical Biochemistry·Hong LiConcetta C DiRusso
Jan 18, 2005·Experimental Eye Research·J SabahL J Takemoto
Feb 9, 2005·The Journal of Biological Chemistry·Concetta C DiRussoPaul N Black
Apr 29, 2006·Bioorganic & Medicinal Chemistry Letters·Christopher BlackburnPrakash Raman
Sep 1, 2007·Journal of Lipid Research·Paul A WatkinsJonathan Pevsner
Sep 29, 2007·Journal of Molecular Neuroscience : MN·Zhenzhen JiaPaul A Watkins
Jul 8, 2008·Archives of Biochemistry and Biophysics·Angel SandovalPaul N Black
Sep 29, 2009·Methods in Molecular Biology·Elsa Arias-BarrauPaul N Black

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Citations

Jun 10, 2010·American Journal of Physiology. Endocrinology and Metabolism·Alaric FalconAndreas Stahl
Mar 20, 2013·Molecular Aspects of Medicine·Courtney M Anderson, Andreas Stahl
Apr 26, 2012·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Biao NieAndreas Stahl
Sep 24, 2015·Biochemical Pharmacology·Constance AhowessoConcetta C DiRusso
Aug 19, 2015·Biochemical and Biophysical Research Communications·Nipun SainiConcetta C DiRusso
Oct 11, 2017·Journal of the American Society of Nephrology : JASN·Shenaz KhanJeffrey R Schelling
Feb 18, 2014·British Journal of Pharmacology·Stephen P H AlexanderUNKNOWN CGTP Collaborators
Jun 16, 2018·Cancer Discovery·Maomao ZhangRichard M White
Oct 8, 2020·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Peishan QiuJing Liu
Aug 28, 2021·Frontiers in Pharmacology·Vojtech DvorakGiulio Superti-Furga

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