Dalcetrapib (JTT-705)

製品コードS2772 バッチS277201

印刷

化学情報

Chemical Structure Synonyms RO4607381 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C23H35NO2S
分子量 389.59 CAS No. 211513-37-0
Solubility (25°C)* 体外 DMSO 78 mg/mL (200.21 mM)
Ethanol 78 mg/mL (200.21 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Homogeneous suspension
0.5% methylcellulose

この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。

 10.000mg/ml (25.67mM) Taking the 1 mL working solution as an example, take 10 mg of this product, add it to 1 ml of 0.5% methylcellulose clear solution, and mix evenly to form a uniform suspension. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Dalcetrapib (JTT-705) is a rhCETP inhibitor with IC50 of 0.2 μM that increases the plasma HDL cholesterol. Phase 3.
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 ≤3 µM and increased at 10 µM. It 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] It inhibits the CETP activity of media in HepG2 in a dose-dependent manner. [3]
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. [1] It has 95% inhibition of CETP activity in male Japanese white rabbits at an oral dose of 30 mg/kg. The compound 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 it 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 this compound 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. [4]

プロトコル(参考用のみ)

キナーゼアッセイ 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.
細胞アッセイ 細胞株 HepG2 cells
濃度 0-30 μM
反応時間 24 hours
実験の流れ 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 the chemical inhibitor Dalcetrapib (JTT-705), which is dissolved in 2% DMSO for 24 hours. Total RNA is used for RT-PCR.
動物実験 動物モデル Syrian hamsters
投薬量 100 mg/kg
投与方法 Oral gavage

参考

  • https://pubmed.ncbi.nlm.nih.gov/20861162/
  • https://pubmed.ncbi.nlm.nih.gov/11000011/
  • https://pubmed.ncbi.nlm.nih.gov/12604506/
  • https://pubmed.ncbi.nlm.nih.gov/15331428/
  • https://pubmed.ncbi.nlm.nih.gov/21175438/

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

CETP inhibitors downregulate hepatic LDL receptor and PCSK9 expression in vitro and in vivo through a SREBP2 dependent mechanism. [ Atherosclerosis, 2014, 235(2):449-62] PubMed: 24950000

長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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