dalcetrapib   Click here for help

GtoPdb Ligand ID: 12972

Synonyms: JTT-705 | JTT705 | RO-4607381 | RO4607381
Compound class: Synthetic organic
Comment: Dalcetrapib (JTT-705) is a cholesteryl ester transfer protein (CETP) inhibitor thioester prodrug. This class of agent was predicted to increase circulating HDL cholesterol as a mechanism to improve cardiovascular health. Dalcetrapib is one of several CETP inhibitors that have failed to demonstrate efficacy in clinical studies [1-4].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 3
Hydrogen bond donors 1
Rotatable bonds 10
Topological polar surface area 71.47
Molecular weight 389.6
XLogP 5.93
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES CCC(CC)CC1(CCCCC1)C(=O)NC2=C(C=CC=C2)SC(=O)C(C)C
Isomeric SMILES CCC(CC)CC1(CCCCC1)C(=O)NC2=CC=CC=C2SC(=O)C(C)C
InChI InChI=1S/C23H35NO2S/c1-5-18(6-2)16-23(14-10-7-11-15-23)22(26)24-19-12-8-9-13-20(19)27-21(25)17(3)4/h8-9,12-13,17-18H,5-7,10-11,14-16H2,1-4H3,(H,24,26)
InChI Key YZQLWPMZQVHJED-UHFFFAOYSA-N
References
1. Filippatos TD, Kei A, Elisaf MS. (2017)
Anacetrapib, a New CETP Inhibitor: The New Tool for the Management of Dyslipidemias?.
Diseases, 5 (4). [PMID:28961179]
2. Hovingh GK, Kastelein JJ, van Deventer SJ, Round P, Ford J, Saleheen D, Rader DJ, Brewer HB, Barter PJ. (2015)
Cholesterol ester transfer protein inhibition by TA-8995 in patients with mild dyslipidaemia (TULIP): a randomised, double-blind, placebo-controlled phase 2 trial.
Lancet, 386 (9992): 452-60. [PMID:26047975]
3. Joy TR, Hegele RA. (2008)
The failure of torcetrapib: what have we learned?.
Br J Pharmacol, 154 (7): 1379-81. [PMID:18536741]
4. Tardif JC, Pfeffer MA, Kouz S, Koenig W, Maggioni AP, McMurray JJV, Mooser V, Waters DD, Grégoire JC, L'Allier PL et al.. (2022)
Pharmacogenetics-guided dalcetrapib therapy after an acute coronary syndrome: the dal-GenE trial.
Eur Heart J, 43 (39): 3947-3956. [PMID:35856777]
5. Tardif JC, Rhéaume E, Lemieux Perreault LP, Grégoire JC, Feroz Zada Y, Asselin G, Provost S, Barhdadi A, Rhainds D, L'Allier PL et al.. (2015)
Pharmacogenomic determinants of the cardiovascular effects of dalcetrapib.
Circ Cardiovasc Genet, 8 (2): 372-82. [PMID:25583994]
6. Yamada K, Brousseau M, Honma W, Iimura A, Imase H, Iwaki Y, Kawanami T, LaSala D, Liang G, Mitani H et al.. (2017)
Discovery of a Novel Piperidine-Based Inhibitor of Cholesteryl Ester Transfer Protein (CETP) That Retains Activity in Hypertriglyceridemic Plasma.
J Med Chem, 60 (20): 8466-8481. [PMID:29035537]