Aleglitazar

Identification

Generic Name
Aleglitazar
DrugBank Accession Number
DB08915
Background

Aleglitazar is an investigational drug from the company Hoffmann–La Roche and is currently in a phase III clinical trial called ALECARDIO. It is being investigated for use in patients with type II diabetes to reduce their risks of cardiovascular mortality and morbidity. Aleglitazar is an agonist at the peroxisome proliferator-activated receptor (PPAR) for both the PPARα and PPARγ receptor subtypes. In the phase II clinical trial called SYNCHRONY, with type II diabetic patients, aleglitazar was able to control both lipid and glucose levels in a synergistic manner while also having limited side effects and toxicity.

Type
Small Molecule
Groups
Investigational
Structure
Weight
Average: 437.508
Monoisotopic: 437.129693541
Chemical Formula
C24H23NO5S
Synonyms
  • Aleglitazar
External IDs
  • R-1439
  • R1439
  • Ro-0728804
  • RO0728804

Pharmacology

Indication

Investigated for use in patients with type II diabetes to reduce their risks of cardiovascular mortality and morbidity.

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Contraindications & Blackbox Warnings
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Pharmacodynamics

Not Available

Mechanism of action

Aleglitazar was rationally designed to be an agonist at the peroxisome proliferator-activated receptor (PPAR) for both the PPARα and PPARγ receptor subtypes. Agonistic action at PPARα controls lipid levels, which improves dyslipidemia, and agonistic action at PPARγ controls glucose levels, which improves insulin sensitivity in diabetes.

TargetActionsOrganism
APeroxisome proliferator-activated receptor alpha
agonist
Humans
APeroxisome proliferator-activated receptor gamma
agonist
Humans
UNuclear receptor coactivator 1Not AvailableHumans
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
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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 phenyl-1,3-oxazoles. These are aromatic heterocyclic compounds containing a 1,3-oxazole substituted at one or more positions by a phenyl group.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Azoles
Sub Class
Oxazoles
Direct Parent
Phenyl-1,3-oxazoles
Alternative Parents
1-benzothiophenes / 2,4,5-trisubstituted oxazoles / Alkyl aryl ethers / Benzene and substituted derivatives / Thiophenes / Heteroaromatic compounds / Oxacyclic compounds / Dialkyl ethers / Carboxylic acids / Azacyclic compounds
show 6 more
Substituents
1-benzothiophene / 2,4,5-trisubstituted 1,3-oxazole / Alkyl aryl ether / Aromatic heteropolycyclic compound / Azacycle / Benzenoid / Benzothiophene / Carbonyl group / Carboxylic acid / Carboxylic acid derivative
show 15 more
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available
Affected organisms
  • Humans and other mammals

Chemical Identifiers

UNII
41T4OAG59U
CAS number
475479-34-6
InChI Key
DAYKLWSKQJBGCS-NRFANRHFSA-N
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
IUPAC Name
(2S)-2-methoxy-3-{4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]-1-benzothiophen-7-yl}propanoic acid
SMILES
CO[C@@H](CC1=CC=C(OCCC2=C(C)OC(=N2)C2=CC=CC=C2)C2=C1SC=C2)C(O)=O

References

Synthesis Reference

Benardeau A, Benz J, Binggeli A, Blum D, Boehringer M, Grether U, Hilpert H, Kuhn B, Marki HP, Meyer M, Puntener K, Raab S, Ruf A, Schlatter D, Mohr P: Aleglitazar, a new, potent, and balanced dual PPARalpha/gamma agonist for the treatment of type II diabetes. Bioorg Med Chem Lett. 2009 May 1;19(9):2468-73. doi: 10.1016/j.bmcl.2009.03.036. Epub 2009 Mar

General References
  1. Henry RR, Lincoff AM, Mudaliar S, Rabbia M, Chognot C, Herz M: Effect of the dual peroxisome proliferator-activated receptor-alpha/gamma agonist aleglitazar on risk of cardiovascular disease in patients with type 2 diabetes (SYNCHRONY): a phase II, randomised, dose-ranging study. Lancet. 2009 Jul 11;374(9684):126-35. doi: 10.1016/S0140-6736(09)60870-9. Epub 2009 Jun 8. [Article]
KEGG Drug
D08845
PubChem Compound
10274777
PubChem Substance
175427152
ChemSpider
8450255
BindingDB
50277897
ChEMBL
CHEMBL519504
ZINC
ZINC000049573657
PDBe Ligand
RO7
Wikipedia
Aleglitazar
PDB Entries
3g8i / 3g9e

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
3CompletedTreatmentCardiovascular Disease, Diabetes Mellitus Type 21
3CompletedTreatmentType 2 Diabetes Mellitus6
3WithdrawnTreatmentDiabetes Mellitus Type 2, Kidney Disease, Chronic1
2CompletedNot AvailableType 2 Diabetes Mellitus1
2CompletedTreatmentType 2 Diabetes Mellitus5

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
PropertyValueSource
Water Solubility0.00797 mg/mLALOGPS
logP4.7ALOGPS
logP4.76Chemaxon
logS-4.7ALOGPS
pKa (Strongest Acidic)4.3Chemaxon
pKa (Strongest Basic)0.93Chemaxon
Physiological Charge-1Chemaxon
Hydrogen Acceptor Count5Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area81.79 Å2Chemaxon
Rotatable Bond Count9Chemaxon
Refractivity127.76 m3·mol-1Chemaxon
Polarizability46.4 Å3Chemaxon
Number of Rings4Chemaxon
Bioavailability1Chemaxon
Rule of FiveYesChemaxon
Ghose FilterYesChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
PropertyValueProbability
Human Intestinal Absorption+0.9929
Blood Brain Barrier-0.6252
Caco-2 permeable-0.5493
P-glycoprotein substrateNon-substrate0.5787
P-glycoprotein inhibitor INon-inhibitor0.9166
P-glycoprotein inhibitor IINon-inhibitor0.5856
Renal organic cation transporterNon-inhibitor0.7685
CYP450 2C9 substrateNon-substrate0.6782
CYP450 2D6 substrateNon-substrate0.7362
CYP450 3A4 substrateSubstrate0.7085
CYP450 1A2 substrateInhibitor0.8073
CYP450 2C9 inhibitorInhibitor0.6557
CYP450 2D6 inhibitorNon-inhibitor0.8705
CYP450 2C19 inhibitorInhibitor0.7626
CYP450 3A4 inhibitorInhibitor0.8033
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.835
Ames testNon AMES toxic0.6579
CarcinogenicityNon-carcinogens0.9581
BiodegradationNot ready biodegradable0.8308
Rat acute toxicity2.2756 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9977
hERG inhibition (predictor II)Non-inhibitor0.7302
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-08mr-0116900000-e68e7709f42bed8682ab
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-0f79-0228900000-d9c13f7f605980f4bebe
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-000i-0519400000-040f508d83e433169481
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-01xd-0219200000-8f2528386738342d2a43
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-002r-9703100000-e84ec12f21d31ad52949
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-0nmi-2973100000-581d77814e3a0cd2ae20
Predicted 1H NMR Spectrum1D NMRNot Applicable
Predicted 13C NMR Spectrum1D NMRNot Applicable
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-200.5345294
predicted
DarkChem Lite v0.1.0
[M-H]-201.44943
predicted
DeepCCS 1.0 (2019)
[M+H]+200.3801294
predicted
DarkChem Lite v0.1.0
[M+H]+203.80742
predicted
DeepCCS 1.0 (2019)
[M+Na]+200.3945294
predicted
DarkChem Lite v0.1.0
[M+Na]+209.95674
predicted
DeepCCS 1.0 (2019)

Targets

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Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleyleth...
Gene Name
PPARA
Uniprot ID
Q07869
Uniprot Name
Peroxisome proliferator-activated receptor alpha
Molecular Weight
52224.595 Da
References
  1. Cavender MA, Lincoff AM: Therapeutic potential of aleglitazar, a new dual PPAR-alpha/gamma agonist: implications for cardiovascular disease in patients with diabetes mellitus. Am J Cardiovasc Drugs. 2010;10(4):209-16. doi: 10.2165/11539500-000000000-00000. [Article]
  2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Yes
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE...
Gene Name
PPARG
Uniprot ID
P37231
Uniprot Name
Peroxisome proliferator-activated receptor gamma
Molecular Weight
57619.58 Da
References
  1. Cavender MA, Lincoff AM: Therapeutic potential of aleglitazar, a new dual PPAR-alpha/gamma agonist: implications for cardiovascular disease in patients with diabetes mellitus. Am J Cardiovasc Drugs. 2010;10(4):209-16. doi: 10.2165/11539500-000000000-00000. [Article]
  2. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Transcription coactivator activity
Specific Function
Nuclear receptor coactivator that directly binds nuclear receptors and stimulates the transcriptional activities in a hormone-dependent fashion. Involved in the coactivation of different nuclear re...
Gene Name
NCOA1
Uniprot ID
Q15788
Uniprot Name
Nuclear receptor coactivator 1
Molecular Weight
156755.44 Da
References
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. [Article]

Drug created at July 01, 2013 16:35 / Updated at February 21, 2021 18:52