Aleglitazar
Explore a selection of our essential drug information below, or:
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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- 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.
Target Actions Organism APeroxisome proliferator-activated receptor alpha agonistHumans APeroxisome proliferator-activated receptor gamma agonistHumans UNuclear receptor coactivator 1 Not Available Humans - 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 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
- 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]
- External Links
- 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
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 Cardiovascular Disease, Diabetes Mellitus Type 2 1 somestatus stop reason just information to hide 3 Completed Treatment Type 2 Diabetes Mellitus 6 somestatus stop reason just information to hide 3 Withdrawn Treatment Diabetes Mellitus Type 2, Kidney Disease, Chronic 1 somestatus stop reason just information to hide 2 Completed Not Available Type 2 Diabetes Mellitus 1 somestatus stop reason just information to hide 2 Completed Treatment Type 2 Diabetes Mellitus 5 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 0.00797 mg/mL ALOGPS logP 4.7 ALOGPS logP 4.76 Chemaxon logS -4.7 ALOGPS pKa (Strongest Acidic) 4.3 Chemaxon pKa (Strongest Basic) 0.93 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 5 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 81.79 Å2 Chemaxon Rotatable Bond Count 9 Chemaxon Refractivity 127.76 m3·mol-1 Chemaxon Polarizability 46.4 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9929 Blood Brain Barrier - 0.6252 Caco-2 permeable - 0.5493 P-glycoprotein substrate Non-substrate 0.5787 P-glycoprotein inhibitor I Non-inhibitor 0.9166 P-glycoprotein inhibitor II Non-inhibitor 0.5856 Renal organic cation transporter Non-inhibitor 0.7685 CYP450 2C9 substrate Non-substrate 0.6782 CYP450 2D6 substrate Non-substrate 0.7362 CYP450 3A4 substrate Substrate 0.7085 CYP450 1A2 substrate Inhibitor 0.8073 CYP450 2C9 inhibitor Inhibitor 0.6557 CYP450 2D6 inhibitor Non-inhibitor 0.8705 CYP450 2C19 inhibitor Inhibitor 0.7626 CYP450 3A4 inhibitor Inhibitor 0.8033 CYP450 inhibitory promiscuity High CYP Inhibitory Promiscuity 0.835 Ames test Non AMES toxic 0.6579 Carcinogenicity Non-carcinogens 0.9581 Biodegradation Not ready biodegradable 0.8308 Rat acute toxicity 2.2756 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9977 hERG inhibition (predictor II) Non-inhibitor 0.7302
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS splash10-08mr-0116900000-e68e7709f42bed8682ab Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS splash10-0f79-0228900000-d9c13f7f605980f4bebe Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS splash10-000i-0519400000-040f508d83e433169481 Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS splash10-01xd-0219200000-8f2528386738342d2a43 Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS splash10-002r-9703100000-e84ec12f21d31ad52949 Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS splash10-0nmi-2973100000-581d77814e3a0cd2ae20 Predicted 1H NMR Spectrum 1D NMR Not Applicable Predicted 13C NMR Spectrum 1D NMR Not Applicable - Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 200.5345294 predictedDarkChem Lite v0.1.0 [M-H]- 201.44943 predictedDeepCCS 1.0 (2019) [M+H]+ 200.3801294 predictedDarkChem Lite v0.1.0 [M+H]+ 203.80742 predictedDeepCCS 1.0 (2019) [M+Na]+ 200.3945294 predictedDarkChem Lite v0.1.0 [M+Na]+ 209.95674 predictedDeepCCS 1.0 (2019)
Targets
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General 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 oleylethanolamide, a naturally occurring lipid that regulates satiety. Receptor for peroxisome proliferators such as hypolipidemic drugs and fatty acids. Regulates the peroxisomal beta-oxidation pathway of fatty acids. Functions as a transcription activator for the ACOX1 and P450 genes. Transactivation activity requires heterodimerization with RXRA and is antagonized by NR2C2. May be required for the propagation of clock information to metabolic pathways regulated by PER2
- Specific Function
- DNA binding
- Gene Name
- PPARA
- Uniprot ID
- Q07869
- Uniprot Name
- Peroxisome proliferator-activated receptor alpha
- Molecular Weight
- 52224.595 Da
References
- 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]
- 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]
- Zhou Y, Zhang Y, Zhao D, Yu X, Shen X, Zhou Y, Wang S, Qiu Y, Chen Y, Zhu F: TTD: Therapeutic Target Database describing target druggability information. Nucleic Acids Res. 2024 Jan 5;52(D1):D1465-D1477. doi: 10.1093/nar/gkad751. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Yes
- Actions
- Agonist
- General 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) and modulates the transcription of its target genes, such as acyl-CoA oxidase. It therefore controls the peroxisomal beta-oxidation pathway of fatty acids. Key regulator of adipocyte differentiation and glucose homeostasis. ARF6 acts as a key regulator of the tissue-specific adipocyte P2 (aP2) enhancer. Acts as a critical regulator of gut homeostasis by suppressing NF-kappa-B-mediated pro-inflammatory responses. Plays a role in the regulation of cardiovascular circadian rhythms by regulating the transcription of BMAL1 in the blood vessels (By similarity)
- Specific Function
- alpha-actinin binding
- Gene Name
- PPARG
- Uniprot ID
- P37231
- Uniprot Name
- Peroxisome proliferator-activated receptor gamma
- Molecular Weight
- 57619.58 Da
References
- 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]
- 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
- 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 receptors, such as for steroids (PGR, GR and ER), retinoids (RXRs), thyroid hormone (TRs) and prostanoids (PPARs). Also involved in coactivation mediated by STAT3, STAT5A, STAT5B and STAT6 transcription factors. Displays histone acetyltransferase activity toward H3 and H4; the relevance of such activity remains however unclear. Plays a central role in creating multisubunit coactivator complexes that act via remodeling of chromatin, and possibly acts by participating in both chromatin remodeling and recruitment of general transcription factors. Required with NCOA2 to control energy balance between white and brown adipose tissues. Required for mediating steroid hormone response. Isoform 2 has a higher thyroid hormone-dependent transactivation activity than isoform 1 and isoform 3
- Specific Function
- chromatin binding
- Gene Name
- NCOA1
- Uniprot ID
- Q15788
- Uniprot Name
- Nuclear receptor coactivator 1
- Molecular Weight
- 156755.44 Da
References
- 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