Anacetrapib (MK-0859)

製品コードS2748 バッチS274805

印刷

化学情報

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

C30H25F10NO3
分子量 637.51 CAS No. 875446-37-0
Solubility (25°C)* 体外 DMSO 100 mg/mL (156.86 mM)
Ethanol 100 mg/mL (156.86 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.
Clear solution
30%PEG400 0.5%Tween80 5%propylene glycol

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 (15.69mM) Taking the 1 mL working solution as an example, add 300 μL of 33.33 mg/ml clarified PEG400 stock solution to 5 μL of Tween80, mix evenly to clarify it; add 50 μL Propylene glycol to the above system, mix evenly to clarify it; then continue to add 645 μL ddH2O Dilute to 1 mL. 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 Anacetrapib (MK0859)は、rhCETPおよび変異型CETP(C13S)の強力で選択的かつ可逆的な阻害剤であり、IC50はそれぞれ7.9 nMおよび11.8 nMです。HDL-Cを増加させ、LDL-Cを減少させ、アルドステロンや血圧を上昇させません。フェーズ3。
in vitro Anacetrapib (MK-0859) is not only able to increase HDL-cholesterol, but also further decreases LDL-cholesterol when taken in combination with a statin. It dose-dependently and significantly decreases the transfer of CE from HDL3 to HDL2. This compound doesn't affect the amount of [14C]-dalcetrapibthiol bound to rhCETP. It decreases pre-β-HDL formation by more than 46%. Anacetrapib potently blocks CE and TG transfer in 95% human serum.
in vivo In a dyslipidemic hamster model, 60 mg/kg/day Anacetrapib (MK-0859) for 2 weeks results in a 94% reduction in CETP activity and 47% increase in HDL-cholesterol compared with control animals; non-HDL-cholesterol concentrations are not affected. This compound also promotes reverse cholesterol transport from macrophages, and leads to a 30% increase in fecal cholesterol content. HDL from it-treated hamsters reveals an increase in SR-B1- and ABCG1-mediated efflux compared with controls. After oral administration of [14C]Anacetrapib at 10 mg/kg, ∼80 and 90% of the radioactive dose is recovered over 48 hous postdose from rats and monkeys, respectively. The majority of the administered radioactive dose is excreted unchanged in feces in both species.

プロトコル(参考用のみ)

キナーゼアッセイ Radioactive assays
The ability of Anacetrapib (MK-0859) to block CETP-mediated CE and TG transfer is measured by radioactive CETP transfer assay with 2% human serum. The procedure is similar to the 95% human serum transfer assay, except that purified human HDL (128 μg/mL) and [3H] cholesteryl oleate or [3H] triolein-labeled LDL are used as acceptor and donor particles, respectively. The [3H] cholesteryl oleate or [3H] triolein from exogenous LDL to HDL is transferred by purified recombinant CETP (30 nM) in standard CETP Buffer (50 mM Tris pH 7.4, 100 nM NaCl, and 1 mM EDTA) with 2% human serum. The transfer reaction is terminated by precipitation of LDL with one volume of ice cold human serum and 2 volumes of 20% W/V PEG 8000. The samples are centrifuged and an aliquot of the HDL-containing supernatant is counted by liquid scintillation. Counts present in the supernatant for controls (without CETP addition) are subtracted from those reactivated with CETP to correct for non-specific transfer.
動物実験 動物モデル Adult male Sprague-Dawley rats weighing 280 to 330 g
投薬量 2.5 mL/kg (2.5, 25, 50, 250 mg/mL)
投与方法 Oral gavage

参考

  • https://pubmed.ncbi.nlm.nih.gov/20861162/
  • https://pubmed.ncbi.nlm.nih.gov/20458119/
  • https://pubmed.ncbi.nlm.nih.gov/20016052/

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：

Inhibition of Cholesteryl Ester Transfer Protein Preserves High-Density Lipoprotein Cholesterol and Improves Survival in Sepsis [ Circulation, 2021, 143(9):921-934] PubMed: 33228395
Mechanism of Inhibition of Cholesteryl Ester Transfer Protein by Small Molecule Inhibitors. [ J Phys Chem B, 2016, 120(33):8254-63] PubMed: 27111423
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。

各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。