NG-497 is an inhibitor of adipose triglyceride lipase (ATGL; IC50 = 1 µM), also known as patatin-like phospholipase domain-containing protein 2 (PNPLA2).1 It is selective for ATGL over PNPLA1, PNPLA3, PNPLA4, and PNPLA5 at 100 µM. NG-497 selectively inhibits the triacylglycerol hydrolase activity of human and rhesus monkey ATGL over rat, dog, and marmoset ATGL, which it inhibits by less than 20% at 50 µM, and over mouse, goat, and pig ATGL at which it is inactive at 50 µM. NG-497 inhibits fatty acid and glycerol release induced by isoproterenol in human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes (IC50 = 1.5 µM for both). It also inhibits forskolin-induced fatty acid release in primary human adipocytes.
1.Grabner, G.F., Guttenberger, N., Mayer, N., et al.Small-molecule inhibitors targeting lipolysis in human adipocytesJ. Am. Chem. Soc.144(14)6237-6250(2022)