Torcetrapib
Explore a selection of our essential drug information below, or:
Identification
- Generic Name
- Torcetrapib
- DrugBank Accession Number
- DB06281
- Background
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.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
- Weight
- Average: 600.4733
Monoisotopic: 600.167061143 - Chemical Formula
- C26H25F9N2O4
- Synonyms
- Torcetrapib
- External IDs
- CP 529,414
- CP-529,414
- CP-529414
Pharmacology
- Indication
Investigated for use/treatment in peripheral vascular disease and hyperlipidemia.
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- Pharmacodynamics
Not Available
- 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.
Target Actions Organism ACholesteryl ester transfer protein antagonistHumans - Absorption
Not Available
- Volume of distribution
Not Available
- Protein binding
Not Available
- Metabolism
- Not Available
- Route of elimination
Not Available
- Half-life
Not Available
- Clearance
Not Available
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates. View sample adverse effects data in our new Data Library!Improve decision support & research outcomes with our structured adverse effects data.
- Toxicity
Not Available
- Pathways
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
Interactions
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.Not Available
- Food Interactions
- Not Available
Categories
- Drug Categories
- Chemical TaxonomyProvided by Classyfire
- Description
- This compound belongs to the class of organic compounds known as hydroquinolines. These are derivatives of quinoline in which in which at least one double bond in the quinoline moiety are reduced by adding two hydrogen atoms.
- Kingdom
- Organic compounds
- Super Class
- Organoheterocyclic compounds
- Class
- Quinolines and derivatives
- Sub Class
- Hydroquinolines
- Direct Parent
- Hydroquinolines
- Alternative Parents
- Trifluoromethylbenzenes / Methylcarbamates / Organic carbonic acids and derivatives / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organofluorides / Organic oxides / Hydrocarbon derivatives / Carbonyl compounds show 1 more
- Substituents
- Alkyl fluoride / Alkyl halide / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Carbamic acid ester / Carbonic acid derivative / Carbonyl group / Hydrocarbon derivative / Methylcarbamate show 11 more
- Molecular Framework
- Aromatic heteropolycyclic compounds
- External Descriptors
- carbamate ester, quinolines, (trifluoromethyl)benzenes (CHEBI:49203)
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- 4N4457MV2U
- CAS number
- 262352-17-0
- InChI Key
- CMSGWTNRGKRWGS-NQIIRXRSSA-N
- InChI
- 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
- IUPAC Name
- ethyl (2R,4S)-4-({[3,5-bis(trifluoromethyl)phenyl]methyl}(methoxycarbonyl)amino)-2-ethyl-6-(trifluoromethyl)-1,2,3,4-tetrahydroquinoline-1-carboxylate
- SMILES
- CCOC(=O)N1[C@H](CC)C[C@H](N(CC2=CC(=CC(=C2)C(F)(F)F)C(F)(F)F)C(=O)OC)C2=C1C=CC(=C2)C(F)(F)F
References
- General References
- Perez-Castrillon JL, Duenas-Laita A: New approaches to atherosclerotic cardiovascular disease. the potentialities of torcetrapib. Recent Pat Cardiovasc Drug Discov. 2006 Jan;1(1):109-14. [Article]
- External Links
- PubChem Compound
- 159325
- ChemSpider
- 140123
- BindingDB
- 50312718
- ChEBI
- 49203
- ChEMBL
- CHEMBL479527
- ZINC
- ZINC000008214714
- PDBe Ligand
- 0RP
- Wikipedia
- Torcetrapib
- PDB Entries
- 4ews
Clinical Trials
- Clinical Trials
Clinical Trial & Rare Diseases Add-on Data Package
Explore 4,000+ rare diseases, orphan drugs & condition pairs, clinical trial why stopped data, & more. Preview package Phase Status Purpose Conditions Count Start Date Why Stopped 100+ additional columns Unlock 175K+ rows when you subscribe.View sample data3 Completed Treatment Coronary Arteriosclerosis / Coronary Heart Disease (CHD) / Hyperlipidemias 1 somestatus stop reason just information to hide 3 Completed Treatment Dyslipidemia / High Cholesterol / Hyperlipidemias 1 somestatus stop reason just information to hide 3 Completed Treatment Hyperlipidemias 3 somestatus stop reason just information to hide 3 Completed Treatment Hyperlipidemias / Primary Hypercholesterolemia 2 somestatus stop reason just information to hide 3 Completed Treatment Hyperlipoproteinemia Type iv / Hypertriglyceridemias 1 somestatus stop reason just information to hide
Pharmacoeconomics
- Manufacturers
- Not Available
- Packagers
- Not Available
- Dosage Forms
- Not Available
- Prices
- Not Available
- Patents
- Not Available
Properties
- State
- Solid
- Experimental Properties
- Not Available
- Predicted Properties
Property Value Source Water Solubility 0.00589 mg/mL ALOGPS logP 5.29 ALOGPS logP 7.08 Chemaxon logS -5 ALOGPS pKa (Strongest Basic) -1.7 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 0 Chemaxon Polar Surface Area 59.08 Å2 Chemaxon Rotatable Bond Count 10 Chemaxon Refractivity 128.89 m3·mol-1 Chemaxon Polarizability 50.67 Å3 Chemaxon Number of Rings 3 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9282 Blood Brain Barrier + 0.9624 Caco-2 permeable + 0.5171 P-glycoprotein substrate Substrate 0.6547 P-glycoprotein inhibitor I Inhibitor 0.7607 P-glycoprotein inhibitor II Inhibitor 0.8636 Renal organic cation transporter Non-inhibitor 0.8158 CYP450 2C9 substrate Non-substrate 0.8145 CYP450 2D6 substrate Non-substrate 0.7812 CYP450 3A4 substrate Substrate 0.6575 CYP450 1A2 substrate Non-inhibitor 0.6226 CYP450 2C9 inhibitor Non-inhibitor 0.5507 CYP450 2D6 inhibitor Non-inhibitor 0.8653 CYP450 2C19 inhibitor Inhibitor 0.6212 CYP450 3A4 inhibitor Non-inhibitor 0.6518 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.7998 Ames test Non AMES toxic 0.607 Carcinogenicity Non-carcinogens 0.7679 Biodegradation Not ready biodegradable 1.0 Rat acute toxicity 2.7449 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9933 hERG inhibition (predictor II) Inhibitor 0.6011
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 225.958 predictedDeepCCS 1.0 (2019) [M+H]+ 227.78542 predictedDeepCCS 1.0 (2019) [M+Na]+ 233.43266 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Antagonist
- General Function
- Involved in the transfer of neutral lipids, including cholesteryl ester and triglyceride, among lipoprotein particles. Allows the net movement of cholesteryl ester from high density lipoproteins/HDL to triglyceride-rich very low density lipoproteins/VLDL, and the equimolar transport of triglyceride from VLDL to HDL (PubMed:24293641, PubMed:3281933, PubMed:3600759). Regulates the reverse cholesterol transport, by which excess cholesterol is removed from peripheral tissues and returned to the liver for elimination (PubMed:17237796)
- Specific Function
- cholesterol binding
- Gene Name
- CETP
- Uniprot ID
- P11597
- Uniprot Name
- Cholesteryl ester transfer protein
- Molecular Weight
- 54755.74 Da
References
- Suckling K: The ENHANCE Study: an unusual publication of trial data raises questions beyond ezetimibe. Expert Opin Pharmacother. 2008 May;9(7):1067-70. doi: 10.1517/14656566.9.7.1067. [Article]
- Perez-Castrillon JL, Duenas-Laita A: New approaches to atherosclerotic cardiovascular disease. the potentialities of torcetrapib. Recent Pat Cardiovasc Drug Discov. 2006 Jan;1(1):109-14. [Article]
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Inducer
- General Function
- A cytochrome P450 monooxygenase that catalyzes the biosynthesis of aldosterone, the main mineralocorticoid in the human body responsible for salt and water homeostasis, thus involved in blood pressure regulation, arterial hypertension, and the development of heart failure (PubMed:11856349, PubMed:12530636, PubMed:1518866, PubMed:15356073, PubMed:1594605, PubMed:1775135, PubMed:22446688, PubMed:23322723, PubMed:9814482, PubMed:9814506). Catalyzes three sequential oxidative reactions of 11-deoxycorticosterone (21-hydroxyprogesterone), namely 11-beta hydroxylation, followed by two successive oxidations at C18 yielding 18-hydroxy and then 18-oxo intermediates (that would not leave the enzyme active site during the consecutive hydroxylation reactions), ending with the formation of aldosterone (PubMed:11856349, PubMed:12530636, PubMed:1518866, PubMed:1594605, PubMed:1775135, PubMed:22446688, PubMed:23322723, PubMed:9814506). Can also produce 18-hydroxycortisol and 18-oxocortisol, derived from successive oxidations of cortisol at C18, normally found at very low levels, but significantly increased in primary aldosteronism, the most common form of secondary hypertension (PubMed:15356073, PubMed:9814482). Mechanistically, uses molecular oxygen inserting one oxygen atom into a substrate and reducing the second into a water molecule. Two electrons are provided by NADPH via a two-protein mitochondrial transfer system comprising flavoprotein FDXR (adrenodoxin/ferredoxin reductase) and nonheme iron-sulfur protein FDX1 or FDX2 (adrenodoxin/ferredoxin) (PubMed:11856349, PubMed:1594605, PubMed:23322723, PubMed:9814506). Could also be involved in the androgen metabolic pathway (Probable)
- Specific Function
- corticosterone 18-monooxygenase activity
- Gene Name
- CYP11B2
- Uniprot ID
- P19099
- Uniprot Name
- Cytochrome P450 11B2, mitochondrial
- Molecular Weight
- 57559.62 Da
References
- Hu X, Dietz JD, Xia C, Knight DR, Loging WT, Smith AH, Yuan H, Perry DA, Keiser J: Torcetrapib induces aldosterone and cortisol production by an intracellular calcium-mediated mechanism independently of cholesteryl ester transfer protein inhibition. Endocrinology. 2009 May;150(5):2211-9. doi: 10.1210/en.2008-1512. Epub 2009 Jan 22. [Article]
Drug created at March 19, 2008 16:21 / Updated at February 21, 2021 18:52