Dalcetrapib(JTT-705,RO4607381)

Molecular Weight (MW)	389.59
Formula	C23H35NO2S
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

Molecular Weight (MW)

389.59

Formula

C23H35NO2S

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

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 Vivo	Treatment 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 model	Syrian hamsters
Formulation & Dosage	Dissolved 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.

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 Vivo

Treatment 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 model

Syrian hamsters

Formulation & Dosage

Dissolved 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.

CAS NO:	211513-37-0
规格:	≥98%

包装	价格(元)
2mg	电议
5mg	电议
10mg	电议
25mg	电议
50mg	电议
100mg	电议