Lalistat 1
目录号 : GC44030
An inhibitor of lysosomal acid lipase
Cas No.:501104-16-1
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
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).
| Cas No. | 501104-16-1 | SDF | |
| 化学名 | 4-morpholinecarboxylic acid, 4-(1-piperidinyl)-1,2,5-thiadiazol-3-yl ester | ||
| Canonical SMILES | O=C(N1CCOCC1)OC2=NSN=C2N3CCCCC3 | ||
| 分子式 | C12H18N4O3S | 分子量 | 298.4 |
| 溶解度 | 20 mg/ml in DMSO, 20 mg/ml in DMF, 20 mg/ml in Ethanol | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.3512 mL | 16.756 mL | 33.5121 mL |
| 5 mM | 0.6702 mL | 3.3512 mL | 6.7024 mL |
| 10 mM | 0.3351 mL | 1.6756 mL | 3.3512 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Physiological difference in autophagic flux in macrophages from 2 mouse strains regulates cholesterol ester metabolism
Arterioscler Thromb Vasc Biol 2013 May;33(5):903-10.PMID:23493286DOI:10.1161/ATVBAHA.112.301041.
Objective: DBA/2 apoE(-/-) mice have ≈10-fold larger lesions than AKR apoE(-/-) mice. The objective of this study was to determine whether macrophages from these 2 strains had altered cholesterol metabolism that might play a role in their divergent atherosclerosis susceptibility. Approach and results: AKR and DBA/2 macrophages incubated with acetylated low-density lipoprotein resulted in higher cholesterol ester (CE) and lower free cholesterol accumulation in the DBA/2 cells. However, these strains had equivalent acetylated low-density lipoprotein uptake and cholesterol esterification activity. Cholesterol efflux from unloaded cells to apolipoprotein A-I or high-density lipoprotein was similar in the 2 strains. However, on acetylated low-density lipoprotein loading, cholesterol efflux was impaired in the DBA/2 cells, but this impairment was corrected by loading in the presence of an inhibitor of cholesterol esterification. Thus, the cholesterol efflux capabilities are similar in these strains, but there seemed to be a defect in lipid droplet-stored CE mobilization in DBA/2 cells. Lalistat 1, a specific inhibitor of lysosomal acid lipase, completely blocked the hydrolysis of lipid droplet-stored CE, implying that lipid droplet autophagy is responsible for CE turnover in these cells. CE turnover was 2-fold slower in DBA/2 versus AKR cells. Autophagic flux, estimated by a fluorescent light chain 3-II reporter and the increase in p62 levels after chloroquine treatment, was higher in AKR versus DBA/2 macrophages, which had an apparent decrease in autophagosome fusion with lysosomes. When autophagy was activated by amino acid starvation, CE levels decreased in DBA/2 cells. Conclusions: Physiological regulation of autophagy in macrophages controls CE accumulation and may modify atherosclerosis susceptibility.