Dalcetrapib

SKU: orb1301120

Description

Dalcetrapib (RO4607381) is a potent inhibitor of cholesteryl ester transfer protein (CETP) with an IC50 of 0.2 μM. This small molecule elevates plasma HDL-C levels and has been utilized in cardiovascular research, including in vitro assays and clinical trials investigating atherosclerosis.

Research Area

Metabolism Research

Key Properties

• CAS Number: 211513-37-0
• MW: 389.59
• Purity: >99.99% (May vary between batches)
• Formula: C₂₃H₃₅NO₂S
• SMILES: CCC(CC)CC1(CCCCC1)C(=O)Nc1ccccc1SC(=O)C(C)C
• Target: CETP
• Solubility: DMSO:72 mg/mL (184.81 mM);H2O:< 1 mg/mL (insoluble or slightly soluble);Ethanol:72 mg/mL (184.81 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (5.13 mM)

Bioactivity

• Target IC50:
  CETP (recombinant human):0.2 μM
• 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.
• 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.
• Cell Research:
  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)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

HDL cholesterol, orally active, inhibit, JTT 705, JTT705, JTT-705, Inhibitor, Cholesteryl ester transfer protein, CETP, Dalcetrapib, RO4607381, RO-4607381, RO 4607381, rhCETP

Compound Identifiers

PubChem CID

6918540