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Dalcetrapib(JTT-705,RO4607381)
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
Dalcetrapib(JTT-705,RO4607381)图片
CAS NO:211513-37-0
规格:≥98%
包装与价格:
包装价格(元)
2mg电议
5mg电议
10mg电议
25mg电议
50mg电议
100mg电议

产品介绍
理化性质和储存条件
Molecular Weight (MW)389.59
FormulaC23H35NO2S
CAS No.211513-37-0
Storage-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)DMSO: 78 mg/mL (200.2 mM)
Water: <1 mg/mL
Ethanol: 78 mg/mL (200.2 mM)
Solubility (In vivo)0.5% methylcellulose: 30 mg/mL
Synonyms

Dalcetrapib; JTT-705; RO-4607381; RO4607381; RO 4607381; JTT705; JTT 705

Chemical Name: S-[2-[[1-(2-ethylbutyl)cyclohexanecarbonyl]amino]phenyl] 2-methylpropanethioate

SMILES Code: CC(C)C(SC1=CC=CC=C1NC(C2(CC(CC)CC)CCCCC2)=O)=O

实验参考方法
In Vitro

In vitro activity: Dalcetrapib modulates CETP activity. Dalcetrapib induces a conformational change in CETP, when added to human plasma. CETP-induced pre-β-HDL formation in human plasma is unchanged by Dalcetrapib ≤3 μM and increased at 10 μM. Dalcetrapib statistically and significantly increases pre-β-HDL formation. Dalcetrapib achieves 50% inhibition of CETP activity in human plasma at a concentration of 9 μM. Dalcetrapib inhibits the CETP activity of media in HepG2 in a dose-dependent manner.


Kinase Assay: The inhibitory potency (IC50) of Dalcetrapib to decrease CE transfer from HDL to LDL by rhCETP and C13S CETP is measured using a scintillation proximity assay kit. Briefly, [3H]CE-labeled HDL donor particles are incubated in the presence of purified CETP proteins (final concentration 0.5 μg/mL) and biotinylated LDL acceptor particles for 3 hours at 37 °C. Subsequently, streptavidin-coupled polyvinyltoluene beads containing liquid scintillation cocktail binding selectively to biotinylated LDL are added, and the amount of [3H]CE molecules transferred to LDL is measured by β counting.


Cell Assay: The HepG2 cells are seeded in 6-well plates and cultured to 70–80% confluence. After being washed with PBS, the cells are incubated with growth medium and a different concentration (0 μM–30 μM) of chemical inhibitor Dalcetrapib and dissolved in 2% DMSO for 24 hours. Total RNA is used for RT-PCR.

In VivoTreatment with Dalcetrapib leads to significant increases in HDL-C levels. In hamsters injected with [3H]cholesterol-labeled autologous macrophages Dalcetrapib significantly increases fecal elimination of both [3H]neutral sterols and [3H]bile acids. Dalcetrapib increases plasma HDL-[3H]cholesterol. Dalcetrapib has 95% inhibition of CETP activity in male Japanese white rabbits at an oral dose of 30 mg/kg. Dalcetrapib increases the plasma HDL cholesterol level by 27% and 54%, respectively, when given at oral doses of 30 mg/kg or 100 mg/kg once a day for 3 days to male Japanese white rabbits. Treatment with Dalcetrapib markedly increases serum levels of HDL-C. The ratio of HDL2-C to HDL3-C is significantly higher in Dalcetrapib–treated rabbits than in control rabbits at 5 and 7 months, indicating that the inhibition of CETP activity by Dalcetrapib changes the distribution of HDL subfractions and preferentially increases HDL2-C levels. Dalcetrapib treatment increases serum paraoxonase activity and HDL-associated platelet-activating factor acetylhydrolase activity, but decreases the plasma lysophosphatidylcholine concentration.
Animal modelSyrian hamsters
Formulation & DosageDissolved in 0.5% methylcellulose; 100 mg/kg; Oral gavage
References

J Lipid Res. 2010 Dec;51(12):3443-54; J Med Chem. 2000 Sep 21;43(19):3566-72.