aleglitazar   Click here for help

GtoPdb Ligand ID: 7405

Synonyms: R-1439 | Ro-0728804
PDB Ligand
Compound class: Synthetic organic
Comment: Aleglitazar is a dual PPARα/δ agonist, or 'glitazar'.
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 Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). 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 4
Hydrogen bond donors 1
Rotatable bonds 9
Topological polar surface area 110.03
Molecular weight 437.13
XLogP 4.27
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES COC(C(=O)O)Cc1ccc(c2c1scc2)OCCc1nc(oc1C)c1ccccc1
Isomeric SMILES CO[C@H](C(=O)O)Cc1ccc(c2c1scc2)OCCc1nc(oc1C)c1ccccc1
InChI InChI=1S/C24H23NO5S/c1-15-19(25-23(30-15)16-6-4-3-5-7-16)10-12-29-20-9-8-17(14-21(28-2)24(26)27)22-18(20)11-13-31-22/h3-9,11,13,21H,10,12,14H2,1-2H3,(H,26,27)/t21-/m0/s1
InChI Key DAYKLWSKQJBGCS-NRFANRHFSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
No information available.
Summary of Clinical Use Click here for help
The hope for this drug is that it would reduce cardiovascular mortality and morbidity in patients with type II diabetes mellitus, however it failed at Phase 3 evaluation in diabetes patients with acute coronary symdrome due to safety concerns. Aleglitazar treatment was associated with increased bone fractures, heart failure and gastrointestinal bleeding. Subsequently, all Phase 3 aleglitazar trials were terminated.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Aleglitazar is an agonist of the PPARs, PPARα and PPARγ. Activation of PPARα controls circulating lipid levels and PPARγ controls glucose levels and improves insulin sensitivity. These comined effects are intended to improve both glucose control and heart health in type II diabetics.
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT01042769 A Study With Aleglitazar in Patients With a Recent Acute Coronary Syndrome and Type 2 Diabetes Mellitus Phase 3 Interventional Hoffmann-La Roche
NCT00388518 A Study of Aleglitazar in Patients With Type 2 Diabetes Phase 2 Interventional Hoffmann-La Roche 1