The connections between C75 and obesity drug-target pathways.
Obesity and its attendant disorders, such as Type II diabetes, have reached epidemic proportions in the USA, and their prevalence is increasing globally. C75 is a small-molecule inhibitor of fatty acid synthase (FAS) and a stimulator of carnitine palmitoyl 1 activity, which causes profound weight loss in mice. Although C75 is not a compound that is destined for human drug development, it has provided two potential pathways to target in obesity therapy: fatty acid synthesis and fatty acid oxidation. In this article, we discuss the latest data challenging the relationship between fatty acid synthase inhibition and C75-induced anorexia.
Kuhajda
Francis P
FP
Department of Pathology, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. fkuhajda@jhmi.edu
Landree
Leslie E
LE
Ronnett
Gabriele V
GV
D015107:4-Butyrolactone / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D055372:AMP-Activated Protein Kinases; D000818:Animals; D000855:Anorexia / Q000209:etiology; D002334:Carnitine O-Palmitoyltransferase / Q000378:metabolism; D004195:Disease Models, Animal; D004435:Eating / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors*; D005227:Fatty Acids / Q000378:metabolism; D005247:Feeding Behavior / Q000187:drug effects; D007031:Hypothalamus / Q000187:drug effects / Q000201:enzymology; D051379:Mice; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors; D009765:Obesity / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D012249:Rhombencephalon / Q000187:drug effects / Q000201:enzymology
C406734:4-methylene-2-octyl-5-oxofuran-3-carboxylic acid; D004791:Enzyme Inhibitors; D005227:Fatty Acids; D009097:Multienzyme Complexes; D002334:Carnitine O-Palmitoyltransferase; D064429:Fatty Acid Synthases; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D015107:4-Butyrolactone