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Identification
NameAleglitazar
Accession NumberDB08915  (DB08483)
TypeSmall Molecule
GroupsInvestigational
Description

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.

Structure
Thumb
SynonymsNot Available
Prescription ProductsNot Available
Generic Prescription ProductsNot Available
Over the Counter ProductsNot Available
International BrandsNot Available
Brand mixturesNot Available
SaltsNot Available
CategoriesNot Available
CAS number475479-34-6
WeightAverage: 437.508
Monoisotopic: 437.129693541
Chemical FormulaC24H23NO5S
InChI KeyDAYKLWSKQJBGCS-RNZRUAGMNA-N
InChI
InChI=1/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-/s2
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
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as benzothiophenes. These are organic compounds containing a benzene fused to a thiepine ring (a five-membered ring with six carbon atoms and one sulfur atom).
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassBenzothiophenes
Sub ClassNot Available
Direct ParentBenzothiophenes
Alternative Parents
Substituents
  • Benzothiophene
  • 2,4,5-trisubstituted 1,3-oxazole
  • Alkyl aryl ether
  • Benzenoid
  • Monocyclic benzene moiety
  • Heteroaromatic compound
  • Thiophene
  • Oxazole
  • Azole
  • Oxacycle
  • Azacycle
  • Monocarboxylic acid or derivatives
  • Ether
  • Dialkyl ether
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External DescriptorsNot Available
Pharmacology
IndicationInvestigated for use in patients with type II diabetes to reduce their risks of cardiovascular mortality and morbidity.
PharmacodynamicsNot Available
Mechanism of actionAleglitazar 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.
AbsorptionNot Available
Volume of distributionNot Available
Protein bindingNot Available
MetabolismNot Available
Route of eliminationNot Available
Half lifeNot Available
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 substrateInhibitor0.6557
CYP450 2D6 substrateNon-inhibitor0.8705
CYP450 2C19 substrateInhibitor0.7626
CYP450 3A4 substrateInhibitor0.8033
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
Pharmacoeconomics
ManufacturersNot Available
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
StateSolid
Experimental PropertiesNot 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 RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
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 Reference
  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. Pubmed
External Links
ATC CodesNot Available
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug InteractionsNot Available
Food InteractionsNot Available

Targets

1. Peroxisome proliferator-activated receptor alpha

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Peroxisome proliferator-activated receptor alpha Q07869 Details

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. Pubmed
  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. Pubmed

2. Peroxisome proliferator-activated receptor gamma

Kind: protein

Organism: Human

Pharmacological action: yes

Actions: agonist

Components

Name UniProt ID Details
Peroxisome proliferator-activated receptor gamma P37231 Details

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. Pubmed
  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. Pubmed

3. Nuclear receptor coactivator 1

Kind: protein

Organism: Human

Pharmacological action: unknown

Components

Name UniProt ID Details
Nuclear receptor coactivator 1 Q15788 Details

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. Pubmed

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Drug created on July 01, 2013 10:35 / Updated on September 26, 2013 14:39