Home Metabolism CETP inhibitor Dalcetrapib (JTT-705)

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Dalcetrapib (JTT-705) CETP inhibitor

Cat.No.S2772

Dalcetrapib (JTT-705) is a rhCETP inhibitor with IC50 of 0.2 μM that increases the plasma HDL cholesterol. This compound is in Phase 3.
Dalcetrapib (JTT-705) CETP inhibitor Chemical Structure

Chemical Structure

Molecular Weight: 389.59

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Quality Control

Batch: S277201 DMSO]78 mg/mL]false]Ethanol]78 mg/mL]false]Water]Insoluble]false Purity: 99.73%
99.73

Solubility

In vitro
Batch:

DMSO : 78 mg/mL (200.21 mM)
(Moisture-contaminated DMSO may reduce solubility. Use fresh, anhydrous DMSO.)

Ethanol : 78 mg/mL

Water : Insoluble

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In vivo
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Chemical Information, Storage & Stability

Molecular Weight 389.59 Formula

C23H35NO2S

 Storage (From the date of receipt)
CAS No. 211513-37-0 Download SDF Storage of Stock Solutions

Synonyms RO4607381 Smiles CCC(CC)CC1(CCCCC1)C(=O)NC2=CC=CC=C2SC(=O)C(C)C

Mechanism of Action

Targets/IC50/Ki
rhCETP
0.2 μM
In vitro
Dalcetrapib (JTT-705) modulates CETP activity and induces a conformational change in CETP when added to human plasma. CETP-induced pre-β-HDL formation in human plasma is unchanged by this compound at ≤3 µM and increased at 10 µM. It statistically and significantly increases pre-β-HDL formation. Dalcetrapib achieves 50% inhibition of CETP activity in human plasma at a concentration of 9 μM. It also inhibits the CETP activity of media in HepG2 in a dose-dependent manner.
Kinase Assay
Inhibition of rhCETP and C13S CETP-mediated transfer of CE from HDL to LDL
The inhibitory potency (IC50) of Dalcetrapib (JTT-705) 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.
In vivo
Treatment with Dalcetrapib (JTT-705) leads to significant increases in HDL-C levels. In hamsters injected with [3H]cholesterol-labeled autologous macrophages, it significantly increases fecal elimination of both [3H]neutral sterols and [3H]bile acids. This compound also increases plasma HDL-[3H]cholesterol. It has 95% inhibition of CETP activity in male Japanese white rabbits at an oral dose of 30 mg/kg. When given at oral doses of 30 mg/kg or 100 mg/kg once a day for 3 days to male Japanese white rabbits, it increases the plasma HDL cholesterol level by 27% and 54%, respectively. Treatment with this compound 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 it changes the distribution of HDL subfractions and preferentially increases HDL2-C levels. Its treatment increases serum paraoxonase activity and HDL-associated platelet-activating factor acetylhydrolase activity, but decreases the plasma lysophosphatidylcholine concentration.
References
  • [4] https://pubmed.ncbi.nlm.nih.gov/15331428/
  • [5] https://pubmed.ncbi.nlm.nih.gov/21175438/

Clinical Trial Information

(data from https://clinicaltrials.gov, updated on 2024-05-22)

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT04676867 Completed
Covid19
DalCor Pharmaceuticals|The Montreal Health Innovations Coordinating Center (MHICC)|Covance
 January 11 2021 Phase 2
NCT01363999 Completed
Healthy Volunteer
Hoffmann-La Roche
 June 2011 Phase 1

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