EG668114 Inhibitors

The class of compounds known as Lipo2 inhibitors encompasses a variety of chemicals that can interact with and modulate the activity of lipases, enzymes that play a crucial role in lipid metabolism by hydrolyzing fats. Inhibitors in this class operate through diverse mechanisms, such as the formation of irreversible acyl-enzyme complexes, competitive binding to the active site, or indirect modulation of enzyme activity through alterations in lipid metabolism. Orlistat and Tetrahydrolipstatin, both sharing the same CAS number, exemplify direct inhibitors that covalently bind to the serine residue within the enzyme's active site, effectively blocking access to substrates and ceasing lipase function. This action is mirrored by other irreversible inhibitors, such as Ebelactone A and B, Methylarachidonyl fluorophosphonate, Paraoxon, and Diethyl p-nitrophenyl phosphate, which also form stable complexes with the active site serine, leading to sustained enzyme inactivation.

Conversely, certain compounds like Atorvastatin and Simvastatin, while not lipase inhibitors per se, can result in decreased lipase activity by reducing the availability of lipid substrates through the inhibition of HMG-CoA reductase, a key enzyme in cholesterol synthesis. Cerulenin, another inhibitor, targets fatty acid synthase, thus indirectly diminishing the pool of fatty acids that could serve as lipase substrates. In addition to these, compounds such as Lalistat 2 and URB602 specifically inhibit lysosomal acid lipase and monoacylglycerol lipase, respectively, by direct binding to the catalytic site, which underscores the diversity of targets within the lipase family that Lipo2 inhibitors can address.