MBOAT2 Inhibitors

Chemical inhibitors of MBOAT2 include Orlistat, which is known to be a potent lipase inhibitor. By inhibiting lipases, Orlistat impedes the transfer of fatty acyl groups to glycerolipids, a key process that MBOAT2 regulates. This inhibition effectively reduces the functional activity of MBOAT2 by limiting its ability to participate in lipid metabolism. Similarly, Cerulenin and C75 target the fatty acid synthesis pathway. Cerulenin acts by inhibiting fatty acid synthase, thereby depleting the levels of fatty acids that serve as substrates for MBOAT2. The reduction in substrate availability directly decreases the enzymatic action of MBOAT2. C75 operates on the same principle, where the inhibition of fatty acid synthase leads to a substrate scarcity for MBOAT2, thus functionally hindering its operation. Betulinic Acid introduces changes to lipid composition by inhibiting stearoyl-CoA desaturase. These alterations can result in a reduced substrate pool for MBOAT2, and the consequential limitation on its activity underscores the functional inhibition imparted by Betulinic Acid.

In addition to these substrate-focused inhibitors, Triacsin C targets acyl-CoA synthetase, leading to a decrease in the acyl-CoA pool. This reduction directly affects MBOAT2 as it relies on these molecules for its enzymatic activity. Tunicamycin's inhibition of N-linked glycosylation, an essential process for the folding and function of membrane proteins, could impair the proper functioning of MBOAT2. Suramin disrupts growth factor-receptor interactions, which can lead to decreased MBOAT2 activity by altering the signaling pathways essential for its function. PD 169316 and LY294002 act on kinase pathways; PD 169316 inhibits p38 MAPK, potentially reducing the phosphorylation and activity of MBOAT2, while LY294002 inhibits the PI3K/AKT pathway, affecting the phosphorylation status and activity of proteins like MBOAT2. GW4869 disrupts the levels of ceramide and the structure of lipid rafts, which can diminish MBOAT2 activity by altering the lipid microenvironment crucial for its function. Similarly, Filipin III binds to cholesterol and alters lipid rafts, which can inhibit MBOAT2 activity. Lastly, Brefeldin A disrupts the Golgi apparatus and protein trafficking, which can inhibit the proper localization and function of MBOAT2 within the cellular membrane architecture.