| Description | LCL521 inhibits lysosomal acid sphingomyelinase (ASMase).LCL521 is an acid ceramidase (ACDase) inhibitor. |
| In vitro | LCL521（1 µM）有效抑制了MCF7细胞中的ACDase，但效果是短暂的。LCL521（10 µM）显著降低了鞘氨醇水平，同时增加了神经酰胺，还影响了ACDase蛋白的加工和再生，对ACDase表达产生了双相和可逆的效应，这与细胞内的鞘氨醇和神经酰胺的长期变化相一致。更高浓度的LCL521还抑制了Dihydroceramide脱饱和酶（DES-1）。综上所述，LCL521对ACDase表现出显著的剂量和时间依赖性效应。[2] |
| In vivo | 当使用PDT处理的SCCVII细胞为带瘤的SCCVII小鼠接种疫苗时，辅以LCL521 (75 mg/kg；i.p.)治疗显著抑制了肿瘤生长。这一效应可归因于LCL521有效限制两种主要免疫调节细胞群体（Tregs和骨髓源性抑制细胞，MDSCs）的活性，这些细胞群体已知会阻碍PDT疫苗的功效。LCL521与基于PDT的抗肿瘤机制的相互作用主要受免疫系统的影响，包括抑制免疫调节细胞的效应，也可能间接增强直接杀死肿瘤细胞的作用。[3] |
| molecular weight | 592.77 |
| Molecular formula | C31H52N4O7 |
| CAS | 1226851-11-1 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 148.5 mg/mL (250.5 mM), Sonication is recommended. Ethanol: 90.0 mg/mL (151.8 mM), Sonication is recommended. |
| References | 1. Bai A, et al. Targeting (cellular) lysosomal acid ceramidase by B13: design, synthesis and evaluation of novel DMG-B13 ester prodrugs. Bioorg Med Chem. 2014 Dec 15;22(24):6933-44. 2. Bai A, et al. Dose dependent actions of LCL521 on acid ceramidase and key sphingolipid metabolites. Bioorg Med Chem. 2018;26(23-24):6067-6075. 3. Korbelik M, et al. Interaction of acid ceramidase inhibitor LCL521 with tumor response to photodynamic therapy and photodynamic therapy-generated vaccine. Int J Cancer. 2016;139(6):1372-1378. 4. Liu F, et al. Ceramide activates lysosomal cathepsin B and cathepsin D to attenuate autophagy and induces ER stress to suppress myeloid-derived suppressor cells. Oncotarget. 2016;7(51):83907-83925. 5. White-Gilbertson S, et al. Polyploid giant cancer cells are dependent on cholesterol for progeny formation through amitotic division. Sci Rep. 2022;12(1):8971. 6. Korbelik M, et al. Mechanistic insights into ceramidase inhibitor LCL521-enhanced tumor cell killing by photodynamic and thermal ablation therapies. Photochem Photobiol Sci. 2020;19(9):1145-1151. |