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| 5mg |
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| 10mg |
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| 25mg |
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| 100mg |
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Purity: ≥98%
Anacetrapib (formerly also known as MK0859; MK-0859), a poly-fluorinated lipophilic compound, is a selective and reversible inhibitor of CETP (Cholesteryl ester transfer protein) and mutant CETP(C13S) with the potential to treat cardiovascular disease. In inhibits CETP and mutant CETP(C13S) with IC50s of 7.9 nM and 11.8 nM. Anacetrapib increases HDL-C and decreases LDL-C, and does not increase aldosterone or blood pressure. It is being developed for the treatment of hypercholesterolemia (elevated cholesterol levels) and prevent cardiovascular disease. Cholesteryl ester transfer protein, also called plasma lipid transfer protein, is a plasma protein that facilitates the transport of cholesteryl esters and triglycerides between the lipoproteins.
| ln Vitro |
The transfer of CE from HDL3 to HDL2 is considerably and dose-dependently reduced by anacetrapib (P<0.001 for doses up to and including 0.1 µM). The amount that [14C]Torcetrapib (0.25 µM) binds to immobilized rhCETP is reduced by 82% and 60%, respectively, by excess anacetrapib (25 µM). Pre-β-HDL production is reduced by over 46% (P<0.001) by anacetrapib at all investigated concentrations (0.1, 1, 3, and 10 µM)[1]. Anacetrapib (ANA) significantly reduces PCSK9 promoter activity; this is seen at 3 µM concentration (−22%, p<0.01), and at 10 µM, it is even lower, at 68% of control. Similarly, Anacetrapib reduces the luciferase activity of B11 cells starting at a concentration of 3 µM and reaches a maximum reduction of 38% of control at 10 µM. Anacetrapib reduces PCSK9 mRNA to 60% of control and LDLR mRNA to 67% of control at 10 µM concentration[2].
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| ln Vivo |
Anacetrapib is administered to hamsters for seven days prior to the injection of [3H]cholesterol-labeled macrophages (day 0). Day 0 HDL-C values are significantly elevated following anacetrapib treatment. Day 3 [3H]cholesterol radioactivity in the HDL fraction is substantially higher than Anacetrapib control values[1]. When compared to a vehicle control, anacetrapib (ANA) medication slightly raises serum levels of total serum cholesterol by around 10% (p<0.05) and serum levels of LDL-C by 26% (p<0.05)[2]. The mean values for terminal half-life, steady-state volume of distribution, and systemic plasma clearance following an intravenous dosage of 0.5 mg/kg are 12 hours, 1.1 L/kg, and 2.3 mL/min/kg, respectively. Anacetrapib has a 38% bioavailability after oral dosage at 5 mg/kg. Exposures (AUC) rise from 23 μM·h at 5 mg/kg to 362 μM·h at 500 mg/kg in a manner that is not dose-proportional. The time to attain peak plasma level (Tmax) ranged from 3 to 4.5 hours, and the peak plasma level (Cmax) ranged from 5 to 26 μM in this dosing range[3].
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| References |
[1]. Niesor EJ, et al. Modulating cholesteryl ester transfer protein activity maintains efficient pre-β-HDL formation and increases reverse cholesterol transport. J Lipid Res. 2010, 51(12), 3443-3454.
[2]. Dong B, et al. CETP inhibitors downregulate hepatic LDL receptor and PCSK9 expression in vitro and in vivo through a SREBP2 dependent mechanism. Atherosclerosis. 2014 Aug;235(2):449-62. [3]. Tan EY, et al. Pharmacokinetics, metabolism, and excretion of anacetrapib, a novel inhibitor of the cholesteryl ester transfer protein, in rats and rhesus monkeys. Drug Metab Dispos. 2010, 38(3), 459-473 |
| Molecular Formula |
C30H25F10NO3
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| Molecular Weight |
637.51
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| CAS # |
875446-37-0
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| SMILES |
FC(C1C([H])=C(C(F)(F)F)C([H])=C(C=1[H])[C@]1([H])[C@]([H])(C([H])([H])[H])N(C(=O)O1)C([H])([H])C1C([H])=C(C(F)(F)F)C([H])=C([H])C=1C1C(=C([H])C(=C(C([H])(C([H])([H])[H])C([H])([H])[H])C=1[H])F)OC([H])([H])[H])(F)F
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| Synonyms |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.75 mg/mL (4.31 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 27.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. Solubility in Formulation 2: 30% PEG400+0.5% Tween80+5% propylene glycol:10 mg/mL (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5686 mL | 7.8430 mL | 15.6860 mL | |
| 5 mM | 0.3137 mL | 1.5686 mL | 3.1372 mL | |
| 10 mM | 0.1569 mL | 0.7843 mL | 1.5686 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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