TMP-153
目录号 : GC45060
A potent ACAT inhibitor
Cas No.:128831-46-9
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Acyl-CoA:cholesterol acyltransferase (ACAT) catalyses the esterification of excess cellular cholesterol with fatty acids and is important for intestinal cholesterol absorption, hepatic lipoprotein secretion, and cholesterol accumulation in vascular tissues. ACAT inhibitors improve plasma lipid profile and ameliorate proteinuria in nephrotic animals. TMP-153 is a quinolyl derivative that inhibits ACAT with IC50 values of 5-10 nM in various animals. At 0.5-1.5 mg/kg, TMP-153 dose-dependently reduces plasma total- and low density lipoprotein cholesterol without affecting high density lipoprotein cholesterol in hamsters. It inhibits cholesterol esterification both in human colonic adenocarcinoma L S180 cells and in human hepatoma HepG2 cells (IC50s = 150 and 330 nM, respectively). When fed as a dietary supplement (ED50 = 0.81 mg/kg/day), TMP-153 reduces hepatic cholesterogenesis in hamsters fed a stock diet.
| Cas No. | 128831-46-9 | SDF | |
| Canonical SMILES | CC1=C(C)C=C2C(C(C3=C(Cl)C=CC=C3)=C(NC(NC4=C(F)C=C(F)C=C4)=O)C=N2)=C1 | ||
| 分子式 | C24H18ClF2N3O | 分子量 | 437.9 |
| 溶解度 | DMF: 10 mg/ml,DMSO: 30 mg/ml | 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.2836 mL | 11.4181 mL | 22.8363 mL |
| 5 mM | 0.4567 mL | 2.2836 mL | 4.5673 mL |
| 10 mM | 0.2284 mL | 1.1418 mL | 2.2836 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。
TMP-153, a novel ACAT inhibitor, inhibits cholesterol absorption and lowers plasma cholesterol in rats and hamsters
Atherosclerosis 1995 Feb;113(1):71-8.PMID:7755657DOI:10.1016/0021-9150(94)05429-m.
Effects of TMP-153, N-[4-(2-chlorophenyl)-6,7-dimethyl-3-quinolyl]-N'-(2,4-difluorophe nyl)urea, on intestinal and hepatic acyl-CoA:cholesterol acyltransferase (ACAT) activities, cholesterol absorption and plasma cholesterol level in rats and hamsters were studied. TMP-153 has IC50 values of around 5-10 nM for the hepatic and intestinal ACAT from various animals. The most potent inhibition was observed in the intestinal ACAT from Golden hamsters (IC50 = 2.3 nM). The inhibition mode of TMP-153 was non-competitive for rat intestinal ACAT. TMP-153 inhibited cholesterol esterification both in human colonic adenocarcinoma cells, LS180, and in human hepatoma cells, HepG2 (IC50 = 150 nM and 330 nM, respectively). [14C]cholesterol and cold cholesterol absorption from the small intestine was markedly inhibited by oral administration of TMP-153 (1 mg/kg) without affecting lymph flow and triglyceride absorption. When the compound was given as a dietary admixture, plasma cholesterol was reduced in rats fed a cholesterol diet (ED50 = 0.25 mg/kg/day), but not in those fed a stock diet. On the other hand, TMP-153 showed more prominent hypocholesterolemic effect in Golden hamsters fed the stock diet (ED50 = 0.81 mg/kg/day) than in those fed the cholesterol diet (ED50 = 8.01 mg/kg/day). In hamsters fed the stock diet, TMP-153 markedly decreased the hepatic unesterified cholesterol in addition to esterified cholesterol content, but did not affect bile flow and the biliary secretion of bile acid and lipids. Different mechanisms for plasma cholesterol lowering by TMP-153 between rats and hamsters was discussed.
TMP-153, a novel ACAT inhibitor, lowers plasma cholesterol through its hepatic action in golden hamsters
Atherosclerosis 1995 Nov;118(1):145-53.PMID:8579624DOI:10.1016/0021-9150(95)05601-r.
The mechanism of the hypocholesterolemic action of N-[4-(2-chlorophenyl)-6,7-dimethyl-3-quinolyl]-N'-(2, 4-difluorophenyl) urea (TMP-153), a potent acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, was studies in Golden hamsters. TMP-153 (0.5-1.5 mg/kg) dose-dependently reduced plasma total- and low density lipoprotein (LDL)-cholesterol without affecting high density lipoprotein (HDL)-cholesterol. TMP-153 markedly reduced the cholesterol influx into the plasma upon intravenous injection of Triton WR-1339. The compound also decreased cholesterol absorption calculated from dietary intake, biliary secretion and the absorption co-efficient. Hepatic cholesterol secretion was calculated by substracting the cholesterol absorption from the cholesterol influx. In hamsters, the liver accounted for 92% of the cholesterol influx with the remaining 8% coming from the intestine, and both were markedly decreased by TMP-153. Thus, it is likely that TMP-153 lowers plasma cholesterol through its hepatic action. In the liver, the compound significantly reduced the unesterified cholesterol content in addition to markedly reducing the content of esterified cholesterol. In accordance with this reduction, the half-life time of [125I]-LDL was significantly shortened by the compound, suggesting an increase in LDL receptors. However, the hepatic cholesterogenesis from [14C]acetate was decreased by TMP-153 treatment. This effect seems to be secondary, since the compound did not inhibit cholesterogenesis from [14C]acetate in HepG2 cells. From the data described above, the contribution of hepatic secretion and intestinal absorption of cholesterol to the plasma cholesterol level in Golden hamsters are discussed.
Cholesterol esterification reduces the neurotoxicity of prions
Neuropharmacology 2008 Jun;54(8):1247-53.PMID:18448139DOI:10.1016/j.neuropharm.2008.04.002.
The transmissible spongiform encephalopathies develop following the conversion of a host-encoded protein (PrP(C)) into abnormally folded, disease-related isoforms (PrP(Sc)). Here we report that three acyl-coenzyme A:cholesterol acyltransferase (ACAT) inhibitors, TMP-153, FR179254 or YIC-C8-434, were more toxic to prion-infected neuronal cell lines (ScGT1 and ScN2a cells) than to their uninfected equivalents (GT1 and N2a cells). The toxicity of ACAT inhibitors for ScGT1 cells was not reversed by the addition of cholesterol esters, rather it was increased by the addition of free cholesterol indicating that the toxicity of ACAT inhibitors was related to the increased free cholesterol content of cells rather than reduced amounts of cholesterol esters. This hypothesis was strengthened by the observation that the addition of free cholesterol killed ScGT1, but not GT1 cells. Treatment with ACAT inhibitors increased caspase-3 activity and prostaglandin E(2) production in ScGT1 cells but not in GT1 cells. The addition of the phospholipase A(2) (PLA(2)) inhibitors (AACOCF(3) or MAFP) reduced prostaglandin E(2) production and protected ScGT1 cells against the toxicity of ACAT inhibitors. These results indicate that cholesterol esterification is an important cellular response that reduces PrP(Sc)-induced activation of PLA(2) and protects against cell death in ScGT1 cells.
Hepatitis C virus infection mediates cholesteryl ester synthesis to facilitate infectious particle production
J Gen Virol 2014 Sep;95(Pt 9):1900-1910.PMID:24859394DOI:10.1099/vir.0.065300-0.
Cholesterol is a critical component of the hepatitis C virus (HCV) life cycle, as demonstrated by its accumulation within infected hepatocytes and lipoviral particles. To cope with excess cholesterol, hepatic enzymes ACAT1 and ACAT2 produce cholesteryl esters (CEs), which are destined for storage in lipid droplets or for secretion as apolipoproteins. Here we demonstrate in vitro that cholesterol accumulation following HCV infection induces upregulation of the ACAT genes and increases CE synthesis. Analysis of human liver biopsy tissue showed increased ACAT2 mRNA expression in liver infected with HCV genotype 3, compared with genotype 1. Inhibiting cholesterol esterification using the potent ACAT inhibitor TMP-153 significantly reduced production of infectious virus, but did not inhibit virus RNA replication. Density gradient analysis showed that TMP-153 treatment caused a significant increase in lipoviral particle density, suggesting reduced lipidation. These data suggest that cholesterol accumulation following HCV infection stimulates the production of CE, a major component of lipoviral particles. Inhibition of CE synthesis reduces HCV particle density and infectivity, suggesting that CEs are required for optimal infection of hepatocytes.