BI99179 is a Selective Type I FASN Inhibitor
Posted On 2021-01-28
Fatty acid synthase (FASN) is a key enzyme involved in neoplastic lipogenesis. In particular, the Overexpression of FASN is common in many cancers. FASN is a metabolic oncogene with an important role in tumor growth and survival, making it an attractive target for cancer therapy. Especially, BI 99179 acts as a potent and selective human FASN inhibitor with an IC50 of 79 nM.
FASN is a key biosynthetic enzyme involved in lipogenesis and the production of long-chain fatty acids from acetyl-coenzyme A (CoA) and malonyl-CoA. FASN plays an important role in tumor cell development and survival. The siRNA knockdown or pharmacological inhibition of FASN results in apoptosis of cancer cells and prolonged survival of xenograft tumors. BI 99179 is a potent and selective inhibitor of type I fatty acid synthase with central exposure. Moreover, BI 99179 acts as a potent and selective inhibitor of human FAS with central exposure upon oral administration in rats.
BI 99179 is a potent FASN inhibitor with an IC50 of 0.6 μM in the mouse N-42 cellular assay. Notably, BI 99179 shows no significant LDH release in the cytotoxicity assay up to 30 μM compound concentration. BI 99179 potently inhibits mouse FAS in addition to the human enzyme applied in the biochemical assay. Furthermore, BI 99179 shows less than 20% inhibition at a concentration of 10 μM in all cases.
All in all, fatty acid synthase acts as a potential therapeutic target in cancer. FASN is crucial in supplying palmitate for protumorigenic activity. In summary, BI 99179 is a potent and selective inhibitor of type I fatty acid synthase with central exposure.
Jörg T Kley, 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.