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Chemical Structure| 875446-37-0 Chemical Structure| 875446-37-0

Structure of Anacetrapib
CAS No.: 875446-37-0

Chemical Structure| 875446-37-0

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Anacetrapib is a potent, selective, reversible rhCETP and mutant CETP (C13S) inhibitor with IC50 of 7.9 nM and 11.8 nM, increases HDL-C and decreases LDL-C, does not increase aldosterone or blood pressure.

Synonyms: MK-0859

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Product Details of Anacetrapib

CAS No. :875446-37-0
Formula : C30H25F10NO3
M.W : 637.51
SMILES Code : O=C1O[C@H](C2=CC(C(F)(F)F)=CC(C(F)(F)F)=C2)[C@H](C)N1CC3=CC(C(F)(F)F)=CC=C3C4=CC(C(C)C)=C(F)C=C4OC
Synonyms :
MK-0859
MDL No. :MFCD16294903

Safety of Anacetrapib

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319-H335
Precautionary Statements:P261-P305+P351+P338

Isoform Comparison

Biological Activity

Target
  • CETP

    rhCETP, IC50:7.9 nM

    Mutant CETP (C13S), IC50:11.8 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
THP1 cells 1 μM CETP inhibitor increased COX-2 and caspase-1 expression and ROS activity PMC11141867
Peripheral blood mononuclear cells (PBMCs) 4 μM Evaluate the effect of paroxetine on autophagy markers, showing that the inducibility of autophagy markers correlates with clinical treatment outcomes PMC11141867
Rat adrenocortical cells 0.1–10 μM 2 hours To evaluate the effect of Anacetrapib on aldosterone release, results showed no significant effect at concentrations up to 10 μM. PMC2440088

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice APOE*3-Leiden.CETP and APOA1.CETP mice Oral (pretreatment) or intravenous injection (post-infection treatment) 10 mg/kg (pretreatment) or 1 mg/kg (post-infection treatment) 1 week (pretreatment) or 6, 30, 54 hours post-infection (post-infection treatment) CETP inhibitor increased HDL-C levels, reduced inflammatory response, and improved survival in pneumosepsis mice PMC11141867
APOE*3Leiden.CETP transgenic mice Atherosclerosis model induced by cholesterol-rich diet Dietary administration 0.03; 0.3; 3; 30 mg/kg/day Daily administration for 21 weeks To evaluate the effects of Anacetrapib on atherosclerosis progression and plaque stability, results showed that Anacetrapib dose-dependently reduced atherosclerotic lesion area and severity, and increased plaque stability PMC4286319
Mice, rats, dogs, rhesus monkeys Normal mice, CETP transgenic mice, anaesthetized rats, anaesthetized dogs, conscious rhesus monkeys I.v. infusion (mice, rats, dogs), p.o. (rhesus monkeys) 10 mg/kg (mice), 5 mg/kg (rats), 1–10 mg/kg (dogs), 500 mg/kg (rhesus monkeys) Single dose, 30 min infusion (mice, rats, dogs), single oral dose (rhesus monkeys) To evaluate the effect of Anacetrapib on blood pressure, results showed no increase in blood pressure in all tested species. PMC2440088
CETP transgenic mice High-fat diet-induced obesity model Intravenous injection 0.2 mg/mL, 2.5 mL/kg per dose Every 12 hours, total five doses To evaluate the effects of anacetrapib on HDL function and metabolism, results showed that anacetrapib increased HDL cholesterol levels but led to liver triglyceride accumulation and insulin resistance in HFD-fed mice PMC6245220
Syrian golden hamsters High-fat diet-induced dyslipidemic model Dietary admix 60 mg/kg/day Once daily for 2 weeks To evaluate the effects of ANA on reverse cholesterol transport and cholesterol excretion, results showed that ANA significantly increased HDL-C levels, promoted macrophage-to-feces cholesterol transport, and increased fecal cholesterol and bile acid excretion. PMC3196228
APOE*3-Leiden.CETP mice Hypercholesterolemia model Dietary supplementation 30 mg/kg body weight per day Once daily for 21 weeks To investigate the effects of anacetrapib on atherosclerosis, it was found that anacetrapib attenuated atherosclerosis development by reducing (V)LDL-C rather than by raising HDL cholesterol. PMC4617395

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT00565006 Ambulatory Blood Pressure Phase 1 Completed - -
NCT00565292 Hypercholesterolemia ... More >> Hyperlipidemia Less << Phase 1 Completed - -
NCT00325455 Hypercholesterolemia ... More >> Mixed Hyperlipemia Less << Phase 2 Terminated - -
NCT00977288 Dyslipidemia Phase 2 Completed - -
NCT00990808 Dyslipidemia Phase 1 Completed - -
NCT00685776 Coronary Heart Disease (CHD) ... More >> CHD Risk-Equivalent Disease Less << Phase 3 Completed - -
NCT02931188 - Completed - United Kingdom ... More >> Clinical Investigation Ward, Addenbrooke's Hospital Cambridge, Cambridgeshire, United Kingdom, CB2 0QQ Less <<
NCT01524289 Hyperlipoproteinemia Type II ... More >> Heterozygous Familial Hypercholesterolemia Less << Phase 3 Active, not recruiting November 30, 2018 -
NCT01114490 Dyslipidemia Phase 1 Completed - -
NCT01717300 Hypercholesterolemia Phase 3 Completed - -
NCT01252953 Atherosclerotic Cardiovascular... More >> Disease Less << Phase 3 Active, not recruiting April 2019 United Kingdom ... More >> CTSU, University of Oxford Oxford, Oxfordshire, United Kingdom, OX3 7LF Less <<
NCT01760460 Dyslipidemia Phase 3 Completed - -
NCT01860729 Hypercholesterolemia Phase 3 Completed - -
NCT01252953 - Active, not recruiting - -
NCT01122667 Dyslipidemia Phase 1 Completed - -
NCT01841684 Hyperlipoproteinemia Type II ... More >> Homozygous Familial Hypercholesterolemia Less << Phase 3 Terminated - -
NCT01824238 Heterozygous Familial Hypercho... More >>lesterolemia (HeFH) Less << Phase 3 Completed - -

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.57mL

0.31mL

0.16mL

7.84mL

1.57mL

0.78mL

15.69mL

3.14mL

1.57mL

References

 

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