Muraglitazar
Identification
- Generic Name
- Muraglitazar
- DrugBank Accession Number
- DB06510
- Background
Muraglitazar (Bristol-Myers Squibb/Merck) is a new agent under investigation for the treatment of patients with type 2 diabetes. It belongs to a novel class of drugs that target the peroxisome proliferator-activated receptors, both alpha and gamma subtypes. In addition to improvements in blood glucose and hemoglobin A1c (HbA1c), muraglitazar treatment is associated with a substantial reduction in triglycerides (TGs), an increase in HDL-C, and a modest decrease in LDL-C levels.
- Type
- Small Molecule
- Groups
- Investigational
- Structure
- Weight
- Average: 516.55
Monoisotopic: 516.18965125 - Chemical Formula
- C29H28N2O7
- Synonyms
- Muraglitazar
- External IDs
- BMS-298585
- BMS-298585-01
- MK-0478
- MK0478
Pharmacology
- Indication
Investigated for use/treatment in diabetes mellitus type 2.
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- Pharmacodynamics
Not Available
- Mechanism of action
Muraglitazar is one of the dual peroxisome proliferator-activated receptor (PPAR) agonists. It interacts with both PPAR alpha and gamma receptors. Working through the PPAR gamma receptor, muraglitazar has very potent insulin-sensitizing effects on liver and muscle to lower the blood sugar levels. working through the PPAR alpha receptor, muraglitazar is very potent in terms of lowering the triglycerides and raising the HDL [high-density lipoprotein] cholesterol and converting small dense LDL [low-density lipoprotein] particles to larger, more buoyant particles, so it promotes a very good lipid profile from the standpoint of prevention of atherosclerosis.
Target Actions Organism UPeroxisome proliferator-activated receptor alpha Not Available Humans UPeroxisome proliferator-activated receptor gamma 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 Browse all" title="About SNP Mediated Effects/ADRs" id="snp-actions-info" class="drug-info-popup" href="javascript:void(0);">
- Not Available
Interactions
- Drug Interactions Learn More" title="About Drug Interactions" id="structured-interactions-info" class="drug-info-popup" href="javascript:void(0);">
- 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.
Drug Interaction Integrate drug-drug
interactions in your softwareAbatacept The metabolism of Muraglitazar can be increased when combined with Abatacept. Abiraterone The metabolism of Muraglitazar can be decreased when combined with Abiraterone. Adalimumab The metabolism of Muraglitazar can be increased when combined with Adalimumab. Adenine The metabolism of Muraglitazar can be decreased when combined with Adenine. Almotriptan The metabolism of Muraglitazar can be decreased when combined with Almotriptan. - 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
- Alpha amino acids and derivatives / Phenoxy compounds / 2,4,5-trisubstituted oxazoles / Methoxybenzenes / Anisoles / Alkyl aryl ethers / Heteroaromatic compounds / Carbamate esters / Organic carbonic acids and derivatives / Oxacyclic compounds show 8 more
- Substituents
- 2,4,5-trisubstituted 1,3-oxazole / Alkyl aryl ether / Alpha-amino acid or derivatives / Anisole / Aromatic heteromonocyclic compound / Azacycle / Benzenoid / Carbamic acid ester / Carbonic acid derivative / Carbonyl group show 18 more
- Molecular Framework
- Aromatic heteromonocyclic compounds
- External Descriptors
- Not Available
- Affected organisms
- Not Available
Chemical Identifiers
- UNII
- W1MKM70WQI
- CAS number
- 331741-94-7
- InChI Key
- IRLWJILLXJGJTD-UHFFFAOYSA-N
- InChI
- InChI=1S/C29H28N2O7/c1-20-26(30-28(37-20)22-6-4-3-5-7-22)16-17-36-24-10-8-21(9-11-24)18-31(19-27(32)33)29(34)38-25-14-12-23(35-2)13-15-25/h3-15H,16-19H2,1-2H3,(H,32,33)
- IUPAC Name
- 2-{[(4-methoxyphenoxy)carbonyl]({4-[2-(5-methyl-2-phenyl-1,3-oxazol-4-yl)ethoxy]phenyl}methyl)amino}acetic acid
- SMILES
- COC1=CC=C(OC(=O)N(CC(O)=O)CC2=CC=C(OCCC3=C(C)OC(=N3)C3=CC=CC=C3)C=C2)C=C1
References
- General References
- Not Available
- External Links
- ChemSpider
- 178524
- BindingDB
- 50150998
- ChEMBL
- CHEMBL186179
- ZINC
- ZINC000049650290
- Wikipedia
- Muraglitazar
Clinical Trials
- Clinical Trials Learn More" title="About Clinical Trials" id="clinical-trials-info" class="drug-info-popup" href="javascript:void(0);">
Phase Status Purpose Conditions Count 3 Completed Treatment Diabetes Mellitus 1 3 Completed Treatment Metabolics Diabetes Nos 1 3 Completed Treatment Type 2 Diabetes Mellitus 5 3 Terminated Treatment Type 2 Diabetes Mellitus 1 2, 3 Completed Treatment Dyslipidemia 1
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 0.0129 mg/mL ALOGPS logP 5.04 ALOGPS logP 4.79 Chemaxon logS -4.6 ALOGPS pKa (Strongest Acidic) 3.19 Chemaxon pKa (Strongest Basic) 0.93 Chemaxon Physiological Charge -1 Chemaxon Hydrogen Acceptor Count 6 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 111.33 Å2 Chemaxon Rotatable Bond Count 12 Chemaxon Refractivity 149.03 m3·mol-1 Chemaxon Polarizability 54.85 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 0 Chemaxon Rule of Five No Chemaxon Ghose Filter No Chemaxon Veber's Rule No Chemaxon MDDR-like Rule Yes Chemaxon - Predicted ADMET Features
- Not Available
Spectra
- Mass Spec (NIST)
- Not Available
- Spectra
- Chromatographic Properties
Collision Cross Sections (CCS)
Adduct CCS Value (Å2) Source type Source [M-H]- 230.2872925 predictedDarkChem Lite v0.1.0 [M-H]- 213.73116 predictedDeepCCS 1.0 (2019) [M+H]+ 230.9507925 predictedDarkChem Lite v0.1.0 [M+H]+ 216.12672 predictedDeepCCS 1.0 (2019) [M+Na]+ 222.03925 predictedDeepCCS 1.0 (2019)
Targets
![](https://go.drugbank.com/assets/locked/DrugTargets2-682eb846d210ae4bf33ca03febccfb57bb1c61318e699b729e5df4dfab2c5b67.png)
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- 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
Enzymes
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- Curator comments
- Data supporting this enzyme action are limited to an in vitro study.
- General Function
- Oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP1A2
- Uniprot ID
- P05177
- Uniprot Name
- Cytochrome P450 1A2
- Molecular Weight
- 58293.76 Da
References
- Zhang D, Wang L, Chandrasena G, Ma L, Zhu M, Zhang H, Davis CD, Humphreys WG: Involvement of multiple cytochrome P450 and UDP-glucuronosyltransferase enzymes in the in vitro metabolism of muraglitazar. Drug Metab Dispos. 2007 Jan;35(1):139-49. Epub 2006 Oct 24. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Retinoic acid binding
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. Isoform 2 lacks transferase activity but acts as a negative reg...
- Gene Name
- UGT1A3
- Uniprot ID
- P35503
- Uniprot Name
- UDP-glucuronosyltransferase 1-3
- Molecular Weight
- 60337.835 Da
References
- Zhang D, Zhang D, Cui D, Gambardella J, Ma L, Barros A, Wang L, Fu Y, Rahematpura S, Nielsen J, Donegan M, Zhang H, Humphreys WG: Characterization of the UDP glucuronosyltransferase activity of human liver microsomes genotyped for the UGT1A1*28 polymorphism. Drug Metab Dispos. 2007 Dec;35(12):2270-80. Epub 2007 Sep 26. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid binding
- Specific Function
- UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform glucuronidates bilirubin IX-alpha to form both the...
- Gene Name
- UGT1A1
- Uniprot ID
- P22309
- Uniprot Name
- UDP-glucuronosyltransferase 1-1
- Molecular Weight
- 59590.91 Da
References
- Zhang D, Zhang D, Cui D, Gambardella J, Ma L, Barros A, Wang L, Fu Y, Rahematpura S, Nielsen J, Donegan M, Zhang H, Humphreys WG: Characterization of the UDP glucuronosyltransferase activity of human liver microsomes genotyped for the UGT1A1*28 polymorphism. Drug Metab Dispos. 2007 Dec;35(12):2270-80. Epub 2007 Sep 26. [Article]
- Zhang D, Wang L, Chandrasena G, Ma L, Zhu M, Zhang H, Davis CD, Humphreys WG: Involvement of multiple cytochrome P450 and UDP-glucuronosyltransferase enzymes in the in vitro metabolism of muraglitazar. Drug Metab Dispos. 2007 Jan;35(1):139-49. Epub 2006 Oct 24. [Article]
- Kind
- Protein
- Organism
- Humans
- Pharmacological action
- Unknown
- Actions
- Substrate
- General Function
- Steroid hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
- Gene Name
- CYP2C8
- Uniprot ID
- P10632
- Uniprot Name
- Cytochrome P450 2C8
- Molecular Weight
- 55824.275 Da
References
- Zhang D, Wang L, Chandrasena G, Ma L, Zhu M, Zhang H, Davis CD, Humphreys WG: Involvement of multiple cytochrome P450 and UDP-glucuronosyltransferase enzymes in the in vitro metabolism of muraglitazar. Drug Metab Dispos. 2007 Jan;35(1):139-49. Epub 2006 Oct 24. [Article]
Drug created at March 19, 2008 16:35 / Updated at February 21, 2021 18:52