Lalistat 2 is an inhibitor of lysosomal acid lipase (LAL), with an IC50 value of 152nM[1]. Lalistat 2, by targeting and inhibiting LAL, will disrupt the function of lysosomes and promote the formation of the pro-inflammatory adipose tissue macrophage (ATM) phenotype[2]. Lalistat 2 has been widely used to specifically measure LAL activity in human blood samples and cells [3].
In vitro, Lalistat 2 treatment at 0.1μM for 4 days led to lipid accumulation in proliferating C2C12 cells, with significant increases in triglyceride and total cholesterol levels[4]. Treatment with 100μM of Lalistat 2 for 7 days led to alterations in the lipid metabolism of mouse bone marrow stromal cells (BMSCs) and impaired cell differentiation[5]. Lalistat 2 treatment (30μΜ; 24h) inhibited the lipase of triglycerides and hormone-sensitive lipase in COS-7 cells[6]. Treatment with 10μM of Lalistat 2 for 6 hours reduced the release of lipid mediators in peritoneal macrophages[7].
References:
[1] 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]. Journal of medicinal chemistry, 2010, 53(14): 5281-5289.
[2] Wehr R, Lindhorst A, Arndt L, et al. Lysosomal exocytosis by macrophages as a druggable mechanism for anti-inflammatory clearance of dead adipocytes in adipose tissue[J]. Cell Death & Disease, 2025.
[3] Hamilton J, Jones I, Srivastava R, et al. A new method for the measurement of lysosomal acid lipase in dried blood spots using the inhibitor Lalistat 2[J]. Clinica chimica acta, 2012, 413(15-16): 1207-1210.
[4] Akhmetshina A, Schooltink L, Amor M, et al. Loss or inhibition of lysosomal acid lipase in vitro leads to cholesteryl ester accumulation without affecting muscle formation or mitochondrial function[J]. BBA advances, 2025, 7: 100135.
[5] Helderman R C, Whitney D G, Duta-Mare M, et al. Loss of function of lysosomal acid lipase (LAL) profoundly impacts osteoblastogenesis and increases fracture risk in humans[J]. Bone, 2021, 148: 115946.
[6] Bradić I, Kuentzel K B, Honeder S, et al. Off-target effects of the lysosomal acid lipase inhibitors Lalistat-1 and Lalistat-2 on neutral lipid hydrolases[J]. Molecular Metabolism, 2022, 61: 101510.
[7] Schlager S, Vujic N, Korbelius M, et al. Lysosomal lipid hydrolysis provides substrates for lipid mediator synthesis in murine macrophages[J]. Oncotarget, 2017, 8(25): 40037.
Lalistat 2是一种溶酶体酸性脂肪酶（LAL）抑制剂，IC50值为152nM[1]。Lalistat 2通过靶向并抑制LAL，将破坏溶酶体功能并促进促炎性脂肪组织巨噬细胞（ATM）表型的形成[2]。Lalistat 2已被广泛用于特异性测定人血液样本和细胞中的LAL活性[3]。
在体外，使用0.1µM的Lalistat 2处理4天，导致增殖的C2C12细胞中脂质积累，甘油三酯和总胆固醇水平显著增加[4]。使用100µM的Lalistat 2处理7天，导致小鼠骨髓基质细胞（BMSCs）的脂质代谢改变并损害细胞分化[5]。Lalistat 2处理（30µM；24小时）抑制了COS-7细胞中的甘油三酯脂肪酶和激素敏感性脂肪酶[6]。使用10µM的Lalistat 2处理6小时，减少了腹腔巨噬细胞中脂质介质的释放[7]。