Fatty acid synthase (FASN) is a multifunctional enzyme involved in the production of fatty
acids for lipid biosynthesis. FASN is overexpressed in multiple diseases like cancer, viral, nonalcoholic
fatty liver disease, and metabolic disorders, making it an attractive target for new drug discovery
for these diseases. In cancer, FASN affects the structure and function of the cellular membrane
by channelizing with signaling pathways along with the post-translational palmitoylation of proteins.
There are several natural and synthetic FASN inhibitors reported in the literature, a few examples are
GSK 2194069 (7.7 nM), imidazopyridine (16 nM), epigallocatechin-3-gallate (42.0 μg/ml) and platensimycin
(300 nM) but except for TVB-2640, none of the aforementioned inhibitors have made into
clinical trials. The present review summarizes the recent advancements made in anticancer drug discovery
targeting FASN. Furthermore, the review also provides insights into the medicinal chemistry of
small molecule inhibitors targeting different FASN enzyme domains, and also critically analyzes the
structural requirements for FASN inhibition with an objective to support rational design and development
of new generation FASN inhibitors with clinical potential in diseases like cancer.