Dalcetrapib

Dalcetrapib is a rhCETP inhibitor with IC50 of 0.2 M.

Product information

CAS Number: 211513-37-0

Molecular Weight: 389.59

Formula: C23H35NO2S

Synonym:

JTT-705

RO4607381

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

Smiles: CC(C)C(=O)SC1=CC=CC=C1NC(=O)C1(CC(CC)CC)CCCCC1

InChiKey: YZQLWPMZQVHJED-UHFFFAOYSA-N

InChi: InChI=1S/C23H35NO2S/c1-5-18(6-2)16-23(14-10-7-11-15-23)22(26)24-19-12-8-9-13-20(19)27-21(25)17(3)4/h8-9,12-13,17-18H,5-7,10-11,14-16H2,1-4H3,(H,24,26)

Technical Data

Appearance: Solid Power

Purity: ≥98% (or refer to the Certificate of Analysis)

Solubility: DMSO: 78 mg/mL(200.21 mM).

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

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.

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.

References:

1. Niesor EJ, et al. Modulating cholesteryl ester transfer protein activity maintains efficient pre-β-HDL formation and increases reverse cholesterol transport. J Lipid Res. 2010, 51(12), 3443-3454.
2. Shinkai H, et al. J Med Chem. bis(2-(Acylamino)phenyl) disulfides, 2-(acylamino)benzenethiols, and S-(2-(acylamino)phenyl) alkanethioates as novel inhibitors of cholesteryl ester transfer protein. 2000, 43(19), 3566-3572.
3. Huang Z, et al. Dual effects on HDL metabolism by cholesteryl ester transfer protein inhibition in HepG2 cells. Am J Physiol Endocrinol Metab. 2003, 284(6), E1210-E1219.

Products are for research use only. Not for human use.