Dalcetrapib

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Chemical Structure| 211513-37-0 同义名 : RO4607381; JTT-705
CAS号 : 211513-37-0
货号 : A162985
分子式 : C23H35NO2S
纯度 : 98%
分子量 : 389.59
MDL号 : MFCD06407886
存储条件：

Pure form Sealed in dry, store in freezer, under -20°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 50 mg/mL(128.34 mM)，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：

0.5% methylcellulose+water 30 mg/mL suspension

生物活性
靶点

  • CETP

    rhCETP, IC50:0.2 μM
描述 Cholesteryl ester transfer protein (CETP) promotes the transfer of cholesteryl esters from high-density lipoprotein (HDL) to very low-density lipoprotein and low-density lipoprotein (LDL). Therefore, CETP inhibition raises high-density lipoprotein cholesterol (HDL-C) levels and decreases LDL-C levels[7]. Dalcetrapib is a CETP inhibitor with IC50 of 0.2 μM that increases the plasma HDL cholesterol[8]. 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[8]. Dalcetrapib achieves 50% inhibition of CETP activity in human plasma at a concentration of 9 μM[9]. Dalcetrapib inhibits the CETP activity of media in HepG2 in a dose-dependent manner[10]. 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[8]. 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[9].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.57mL

0.51mL

0.26mL

12.83mL

2.57mL

1.28mL

25.67mL

5.13mL

2.57mL
参考文献

[1]Niesor EJ, Magg C, et al. Modulating cholesteryl ester transfer protein activity maintains efficient pre-β-HDL formation and increases reverse cholesterol transport. J Lipid Res. 2010 Dec;51(12):3443-54.

[2]Shinkai H, Maeda K, et al. bis(2-(Acylamino)phenyl) disulfides, 2-(acylamino)benzenethiols, and S-(2-(acylamino)phenyl) alkanethioates as novel inhibitors of cholesteryl ester transfer protein. J Med Chem. 2000 Sep 21;43(19):3566-72.

[3]Takubo H, Ishikawa T, et al. Pharmacokinetics and disposition of dalcetrapib in rats and monkeys. Xenobiotica. 2014 Dec;44(12):1117-26.

[4]Briand F, Thieblemont Q, et al. Anacetrapib and dalcetrapib differentially alters HDL metabolism and macrophage-to-feces reverse cholesterol transport at similar levels of CETP inhibition in hamsters. Eur J Pharmacol. 2014 Oct 5;740:135-43.

[5]Shinkai H, Maeda K, et al. bis(2-(Acylamino)phenyl) disulfides, 2-(acylamino)benzenethiols, and S-(2-(acylamino)phenyl) alkanethioates as novel inhibitors of cholesteryl ester transfer protein. J Med Chem. 2000 Sep 21;43(19):3566-72.

[6]Kuhlmann O, Heinig K, et al. Dalcetrapib pharmacokinetics and metabolism in the cynomolgus monkey. Xenobiotica. 2011 May;41(5):430-6.

[7]Kosmas CE, DeJesus E, Rosario D, Vittorio TJ. CETP Inhibition: Past Failures and Future Hopes. Clin Med Insights Cardiol. 2016 Mar 13;10:37-42. doi: 10.4137/CMC.S32667. PMID: 26997876; PMCID: PMC4790583.

[8]Niesor EJ, Magg C, Ogawa N, Okamoto H, von der Mark E, Matile H, Schmid G, Clerc RG, Chaput E, Blum-Kaelin D, Huber W, Thoma R, Pflieger P, Kakutani M, Takahashi D, Dernick G, Maugeais C. Modulating cholesteryl ester transfer protein activity maintains efficient pre-β-HDL formation and increases reverse cholesterol transport. J Lipid Res. 2010 Dec;51(12):3443-54. doi: 10.1194/jlr.M008706. Epub 2010 Sep 22. PMID: 20861162; PMCID: PMC2975716.

[9]Shinkai H, Maeda K, Yamasaki T, Okamoto H, Uchida I. bis(2-(Acylamino)phenyl) disulfides, 2-(acylamino)benzenethiols, and S-(2-(acylamino)phenyl) alkanethioates as novel inhibitors of cholesteryl ester transfer protein. J Med Chem. 2000 Sep 21;43(19):3566-72. doi: 10.1021/jm000224s. PMID: 11000011.

[10]Huang Z, Inazu A, Kawashiri MA, Nohara A, Higashikata T, Mabuchi H. Dual effects on HDL metabolism by cholesteryl ester transfer protein inhibition in HepG2 cells. Am J Physiol Endocrinol Metab. 2003 Jun;284(6):E1210-9. doi: 10.1152/ajpendo.00453.2002. Epub 2003 Feb 25. PMID: 12604506.