Fatty acids are carboxylic acids containing a long aliphatic chain. They are assumed with the diet or synthetized de novo from carbohydrate precursors by the enzyme fatty acid synthase (FAS). This protein plays an important role in tumor development because cancer cells use fatty acids as building blocks to synthetize their cellular membranes. Nevertheless, compounds blocking FAS activity are still lacking.
Cynthia Parrish, GlaxoSmithKline, Collegeville, PA, USA, and colleagues have developed a highly potent, specific and reversible FAS inhibitor. The new drug, GSK2194069 (pictured), inhibits one of the six FAS catalytic domains (namely the β‑ketoacyl synthase domain), thereby blocking the accumulation of fatty acids. As a consequence, the compound potently inhibited the growth of cancer cells in vitro.
GSK2194069 may thus represent a novel tool to treat tumors.
- A human fatty acid synthase inhibitor binds β-ketoacyl reductase in the keto-substrate site,
Mary Ann Hardwicke, Alan R. Rendina, Shawn P. Williams, Michael L. Moore, Liping Wang, Julie A. Krueger, Ramona N. Plant, Rachel D. Totoritis, Guofeng Zhang, Jacques Briand, William A. Burkhart, Kristin K. Brown, Cynthia A, Parrish,
Nat. Chem. Biol. 2014.