NAV

Muraglitazar

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

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
3D
Similar Structures
Weight
Average: 516.55
Monoisotopic: 516.18965125
Chemical Formula
C29H28N2O7
Synonyms
  • Muraglitazar
External IDs
  • BMS-298585
  • BMS-298585-01
  • MK-0478
  • MK0478
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Pharmacology

Indication

Investigated for use/treatment in diabetes mellitus type 2.

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Contraindications & Blackbox Warnings
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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.

TargetActionsOrganism
UPeroxisome proliferator-activated receptor alphaNot AvailableHumans
UPeroxisome proliferator-activated receptor gammaNot 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 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.
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AbataceptThe metabolism of Muraglitazar can be increased when combined with Abatacept.
AbirateroneThe metabolism of Muraglitazar can be decreased when combined with Abiraterone.
AdalimumabThe metabolism of Muraglitazar can be increased when combined with Adalimumab.
AdenineThe metabolism of Muraglitazar can be decreased when combined with Adenine.
AlmotriptanThe 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
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);">
PhaseStatusPurposeConditionsCount
3CompletedTreatmentDiabetes Mellitus1
3CompletedTreatmentMetabolics Diabetes Nos1
3CompletedTreatmentType 2 Diabetes Mellitus5
3TerminatedTreatmentType 2 Diabetes Mellitus1
2, 3CompletedTreatmentDyslipidemia1

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 Solubility0.0129 mg/mLALOGPS
logP5.04ALOGPS
logP4.79Chemaxon
logS-4.6ALOGPS
pKa (Strongest Acidic)3.19Chemaxon
pKa (Strongest Basic)0.93Chemaxon
Physiological Charge-1Chemaxon
Hydrogen Acceptor Count6Chemaxon
Hydrogen Donor Count1Chemaxon
Polar Surface Area111.33 Å2Chemaxon
Rotatable Bond Count12Chemaxon
Refractivity149.03 m3·mol-1Chemaxon
Polarizability54.85 Å3Chemaxon
Number of Rings4Chemaxon
Bioavailability0Chemaxon
Rule of FiveNoChemaxon
Ghose FilterNoChemaxon
Veber's RuleNoChemaxon
MDDR-like RuleYesChemaxon
Predicted ADMET Features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSsplash10-014l-0545290000-35dca1f6e5ab5a814bea
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSsplash10-00xr-2914210000-101afffe3f4ce445e8c3
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSsplash10-002g-6974310000-190060398bc783ad4b36
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSsplash10-0uk9-1901100000-73bc9126951a228dc606
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSsplash10-05y0-7920220000-efed0cd67c3a7e67091f
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSsplash10-010r-4934000000-5ad29d1f6cf5e19c867e
Chromatographic Properties
Collision Cross Sections (CCS)
AdductCCS Value (Å2)Source typeSource
[M-H]-230.2872925
predicted
DarkChem Lite v0.1.0
[M-H]-213.73116
predicted
DeepCCS 1.0 (2019)
[M+H]+230.9507925
predicted
DarkChem Lite v0.1.0
[M+H]+216.12672
predicted
DeepCCS 1.0 (2019)
[M+Na]+222.03925
predicted
DeepCCS 1.0 (2019)

Targets

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Details1. Peroxisome proliferator-activated receptor alpha
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
Details2. Peroxisome proliferator-activated receptor gamma
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

Details1. Cytochrome P450 1A2
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
  1. 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]
Details2. UDP-glucuronosyltransferase 1-3
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
  1. 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]
Details3. UDP-glucuronosyltransferase 1-1
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
  1. 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]
  2. 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]
Details4. Cytochrome P450 2C8
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
  1. 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