Lalistat 1 is an inhibitor of lysosomal acid lipase (LAL; IC50 = 68 nM using purified human LAL). [1] It is selective for LAL over human pancreatic and bovine milk lipoprotein lipases up to a concentration of 10 µM.[2] Lalistat 1 (0.01-10 µM) reduces cholesterol accumulation in lysosome-like storage organelles in GM03123 human fibroblast cells deficient in NPC1, a membrane protein found in late endosomes, in a concentration-dependent manner but has little effect on cholesterol accumulation in NPC1-deficient CHO cells.
Reference
[1]. Rosenbaum, A.I., Rujoi, M., Huang, A.Y., et al. Chemical screen to reduce sterol accumulation in Niemann-Pick C disease cells identifies novel lysosomal acid lipase inhibitors. Biochim Biophys. Acta. 1791(12), 1155-1165 (2009).
[2]. Rosenbaum, A.I., Cosner, C.C., Mariani, C.J., et al. Thiadiazole carbamates: Potent inhibitors of lysosomal acid lipase and potential Niemann-Pick type C disease therapeutics. J. Med. Chem. 53(14), 5281-5289 (2010).