1291779-76-4

BI 99179 is a potent and selective type I fatty acid synthase (FAS) inhibitor with an IC50 of 79 nM. BI 99179 is a tool compound suitable for the in vivo validation of FAS as a target for lipid metabolism related diseases. BI 99179 exhibits significant exposure (both peripheral and central) upon oral administration in rats[1][2].

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%>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).

[1] Kley JT, et al. Discovery of BI 99179, a potent and selective inhibitor of type I fatty acid synthase with central exposure.Bioorg Med Chem Lett. 2011 Oct 1;21(19):5924-7. DOI:10.1016/j.bmcl.2011.07.083
[2] Prosanta K Singha, et al. Evaluation of FASN inhibitors by a versatile toolkit reveals differences in pharmacology between human and rodent FASN preparations and in antiproliferative efficacy in vitro vs. in situ in human cancer cells. Eur J Pharm Sci. 2020 Apr 7;149:105321. DOI:10.1016/j.ejps.2020.105321