| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
|
Purity: ≥98%
Torcetrapib (formerly CP 529414; CP-529,414; CP-529414) is a novel and potent CETP (Cholesteryl ester transfer protein) inhibitor with the potential to lower cholesterol levels and to treat cardiovascular diseases. It inhibits CETP with an IC50 of 37 nM. Torcetrapib is able to elevate plasma HDL-C and reducs non-HDL-C, and thus is being studied to treat hypercholesterolemia (elevated cholesterol levels) and prevent cardiovascular disease.
| Targets |
CETP/cholesteryl ester transfer protein
|
|---|---|
| ln Vitro |
Using the specific activity-adjusted calculation, the IC50 for trocetrapib is 52 and 65 nM for the 3H-HDL and 14C-LDL cholesteryl ester transfer tests, respectively, and 47 and 61 nM using a single exponential decay function[1]. This information is derived from the linear region of the curves, which ranges from 25 to 80 nM. The proliferation of MCF-7 cells was dramatically inhibited by trocetrapib (0, 0.5, 1, 5, and 10 μM)[2]. Torcetrapib at concentrations of 0, 1, 5, 10, and 20 μM does not cause apoptosis in MCF-7 cells[2]. The high affinity binding of trocetrapib (10 μM) to CETP results in the downregulation of CETP expression[2].
|
| ln Vivo |
Torcetrapib increases high-density lipoprotein (HDL) cholesterol and decreases low-density lipoprotein (LDL) cholesterol significantly (3, 10, or 30 mg/kg every day [qd]; oral gavage for 14 days). Additionally, there is a tendency for Torcetrapib to lower triglycerides and very-low-density lipoprotein (VLDL) cholesterol. With trocetapib, the maximum increase in HDL cholesterol is 53%[3].
Cholesteryl ester transfer protein (CETP) plays a key role in high-density lipoprotein (HDL) cholesterol metabolism, but normal mice are deficient in CETP. In this study, transgenic mice expressing both human apolipoprotein B 100 (ApoB-100) and human CETP (hApoB100/hCETP) were used to characterize the effects of CETP inhibition and peroxisome proliferator-activated receptor alpha (PPARalpha) agonism on lipid profiles. Torcetrapib (3, 10, and 30 mg/kg), a CETP inhibitor, fenofibrate (30 mg/kg), a weak PPARalpha agonist, and GW590735 (3 and 10 mg/kg), a potent and selective PPARalpha agonist were given orally for 14 days to hApoB100/hCETP mice and lipid profiles were assessed. The average percentages of HDL, low-density lipoprotein (LDL), and very-low-density lipoprotein (VLDL) cholesterol fractions in hApoB100/hCETP mice were 34.8%, 61.6%, and 3.6%, respectively, which is similar to those of normolipidemic humans. Both torcetrapib and fenofibrate significantly increased HDL cholesterol and reduced LDL cholesterol, and there was a tendency for torcetrapib to reduce VLDL cholesterol and triglycerides. GW590735 significantly increased HDL cholesterol, decreased LDL and VLDL cholesterol, and significantly reduced triglycerides. Maximal increases in HDL cholesterol were 37%, 53%, and 84% with fenofibrate, torcetrapib, and GW590735, respectively. These results, in mice that exhibit a more human-like lipid profile, demonstrate an improved lipid profile with torcetrapib, fenofibrate, and GW590735, and support the use of selective PPARalpha agonism for the treatment of lipid disorders. In addition, these data demonstrate the use of hApoB100/hCETP transgenic mice to identify, characterize, and screen compounds that increase HDL cholesterol.[3] |
| Enzyme Assay |
Cellular Thermal Shift Assay (CETSA)[2]
The protein-drug binding thermal shift assay was employed to test the binding of PL/AP to CETP. Briefly MCF-7 cells grown to 60% confluency in T75 flasks were treated with PL, AP or Torcetrapib for 2 h at 37°C. Cells were trypsinized, counted, and washed twice with 1x PBS. The cell pellet was resuspended in 1 × EDTA-free protease inhibitors and aliquoted into PCR tubes at 1.5 × 106 cells per tube. Tubes were placed in a Veriti® 96-Well Thermal Cycler and incubated for 3 min at 56–74°C with 2°C increments. Tubes were taken out of the thermal cycler and incubated at room temperature for 3 min. Cells were lysed by freeze-thawing the tubes twice in liquid nitrogen and at 25°C for 3 min with vortexing in between freeze-thaw cycles. Immediately after, cells were centrifuged at 14 000 rpm and 4°C for 20 min, and the supernatant was transferred to a clean Eppendorf tube. Protein was quantified using the BCA protein determination kit, and equal amounts of protein (15-20 μg) were subjected to Western blotting for CETP detection. |
| Cell Assay |
Cell Viability Assay
Cell Types: MCF-7 cells Tested Concentrations: 0, 0.5, 1, 5, and 10 μM Incubation Duration: 5 days Experimental Results: Dramatically decreased cell growth. RT-PCR Cell Types: MCF-7 cells Tested Concentrations: 10 μM Incubation Duration: 48 hrs (hours) Experimental Results: Down-regulated CETP mRNA expression. |
| Animal Protocol |
Animal/Disease Models: Male Tg (B6; SJL-TgN (CETP)-TgN (ApoB100)) mice at 6 to 7 weeks of age[3]
Doses: 3, 10, and 30 mg/kg Route of Administration: Orally every day for 14 days Experimental Results: Dramatically Increased HDL cholesterol by 27%, 24%, and 53% in the 3, 10 , and 30 mg/kg groups compared to baseline, respectively, after 14 days of treatment. Dramatically diminished LDL cholesterol by 44% and 35% at 10 and 30 mg/kg compared to baseline, respectively, after 14 days of treatment. |
| References |
|
| Additional Infomation |
Torcetrapib is a member of quinolines, a carbamate ester and a member of (trifluoromethyl)benzenes. It has a role as an anticholesteremic drug and a CETP inhibitor.
Torcetrapib (CP-529414, Pfizer) was developed to treat hypercholesterolemia but its development was halted in 2006 when phase III studies showed excessive mortality in the treatment group receiving a combination of atorvastatin and the study drug. Torcetrapib is a cholesteryl ester transfer protein (CETP) inhibitor that reduces the heterotypic transfer of cholesteryl ester from HDL to LDL and/or VLDL. Torcetrapib failed in phase III trials due to excess deaths. Drug Indication Investigated for use/treatment in peripheral vascular disease and hyperlipidemia. Mechanism of Action Torcetrapib is an inhibitor of cholesteryl ester-transfer protein (CETP) that increases high-density lipoprotein (HDL) cholesterol levels. The drug increases HDL-cholesterol and apolipoprotein A-I levels and decreases LDL-cholesterol and apolipoprotein B levels. The effect is showed in monotherapy and when administered in combination with statins. |
| Molecular Formula |
C26H25F9N2O4
|
|
|---|---|---|
| Molecular Weight |
600.47
|
|
| Exact Mass |
600.167
|
|
| Elemental Analysis |
C, 52.01; H, 4.20; F, 28.47; N, 4.67; O, 10.66
|
|
| CAS # |
262352-17-0
|
|
| Related CAS # |
|
|
| PubChem CID |
159325
|
|
| Appearance |
White to off-white solid powder
|
|
| Density |
1.4±0.1 g/cm3
|
|
| Boiling Point |
504.8±50.0 °C at 760 mmHg
|
|
| Melting Point |
54-58ºC
|
|
| Flash Point |
259.1±30.1 °C
|
|
| Vapour Pressure |
0.0±1.3 mmHg at 25°C
|
|
| Index of Refraction |
1.512
|
|
| LogP |
7.76
|
|
| Hydrogen Bond Donor Count |
0
|
|
| Hydrogen Bond Acceptor Count |
13
|
|
| Rotatable Bond Count |
7
|
|
| Heavy Atom Count |
41
|
|
| Complexity |
889
|
|
| Defined Atom Stereocenter Count |
2
|
|
| SMILES |
CC[C@@H]1C[C@@H](C2=C(N1C(=O)OCC)C=CC(=C2)C(F)(F)F)N(CC3=CC(=CC(=C3)C(F)(F)F)C(F)(F)F)C(=O)OC
|
|
| InChi Key |
CMSGWTNRGKRWGS-NQIIRXRSSA-N
|
|
| InChi Code |
InChI=1S/C26H25F9N2O4/c1-4-18-12-21(19-11-15(24(27,28)29)6-7-20(19)37(18)23(39)41-5-2)36(22(38)40-3)13-14-8-16(25(30,31)32)10-17(9-14)26(33,34)35/h6-11,18,21H,4-5,12-13H2,1-3H3/t18-,21+/m1/s1
|
|
| Chemical Name |
ethyl (2R,4S)-4-[[3,5-bis(trifluoromethyl)phenyl]methyl-methoxycarbonylamino]-2-ethyl-6-(trifluoromethyl)-3,4-dihydro-2H-quinoline-1-carboxylate
|
|
| Synonyms |
|
|
| HS Tariff Code |
2934.99.9001
|
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
|
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.16 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.16 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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.6654 mL | 8.3268 mL | 16.6536 mL | |
| 5 mM | 0.3331 mL | 1.6654 mL | 3.3307 mL | |
| 10 mM | 0.1665 mL | 0.8327 mL | 1.6654 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.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00139061 | Completed | Drug: Torcetrapib/Atorvastatin Drug: Fenofibrate |
Hyperlipidemia | Pfizer | March 2005 | Phase 3 |
| NCT00134511 | Completed | Drug: Torcetrapib/atorvastatin | Hypercholesterolemia, Familial | Pfizer | March 2005 | Phase 3 |
| NCT00134264 | Terminated | Drug: torcetrapib/atorvastatin Drug: atorvastatin |
Coronary Disease Diabetes Mellitus |
Pfizer | July 2004 | Phase 3 |
| NCT00134485 | Completed | Drug: torcetrapib/atorvastatin Drug: atorvastatin |
Hypercholesterolemia, Familial Hyperlipidemia |
Pfizer | March 2005 | Phase 3 |
 |
|---|
 |
 |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA