Biochem/physiol Actions

BI 99179 is a non-cytotoxic (by LDH release; 30 µM, U937) orally available, brain-penetrant, highly potent and selective fatty acid synthase (FAS, FASN) inhibitor (IC₅₀ = 79 nM by cell-free human FAS assay) with little or no inhibitory potency toward a panel of 30 receptors & channels (﹤20% inhibition at 10 µM) and human CYP450 isoenzymes (1A2/2C9/2C19/2D6/3A4 IC₅₀ >10 µM). BI 99179 inhibits cellular FAS activity in vitro (IC₅₀ = 180 nM/human H1975, 600 nM/murine hypothalamic N-42 cells) and increases hypothalamic [malonyl-CoA] in rats in vivo (2 h post 10 mg/kg or 2-24 hr post 100 mg/kg p.o.). Note: adverse effects in rats are reported at day 4 (30 mg/kg) and day 9 (3 mg/kg).