| Description | Dalcetrapib (RO4607381), a rhCETP inhibitor (IC50=0.2 μM), increases the plasma HDL cholesterol. |
| 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. [1] Dalcetrapib achieves 50% inhibition of CETP activity in human plasma at a concentration of 9 μM. [2] Dalcetrapib inhibits the CETP activity of media in HepG2 in a dose-dependent manner. [3] |
| 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. [1] 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. [2] 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. [4] |
| Cell experiments | 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.(Only for Reference) |
| Target activity | CETP (recombinant human):0.2 μM |
| Synonyms | JTT-705, 达塞曲匹, RO4607381 |
| molecular weight | 389.59 |
| Molecular formula | C23H35NO2S |
| CAS | 211513-37-0 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year |
| Solubility | DMSO: 72 mg/mL (184.8 mM) Ethanol: 72 mg/mL (184.8 mM) H2O: < 1 mg/mL (insoluble or slightly soluble) |
| References | 1. Niesor EJ, et al. J Lipid Res. 2010, 51(12), 3443-3454. 2. Shinkai H, et al. J Med Chem. 2000, 43(19), 3566-3572. 3. Huang Z, et al. Am J Physiol Endocrinol Metab. 2003, 284(6), E1210-E1219. 4. Zhang B, et al. Arterioscler Thromb Vasc Biol. 2004, 24(10), 1910-1915. 5. Derks M, et al. Br J Clin Pharmacol. 2010, 70(6), 825-833. |