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

Identification

Name
Muraglitazar
Accession Number
DB06510
Type
Small Molecule
Groups
Investigational
Description

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.

Structure
Thumb
Synonyms
Not Available
External IDs
BMS-298585 / BMS-298585-01 / MK-0478 / MK0478
Categories
UNII
W1MKM70WQI
CAS number
331741-94-7
Weight
Average: 516.55
Monoisotopic: 516.18965125
Chemical Formula
C29H28N2O7
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

Pharmacology

Indication

Investigated for use/treatment in diabetes mellitus type 2.

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 AvailableHuman
UPeroxisome proliferator-activated receptor gammaNot AvailableHuman
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
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteraction
AbirateroneThe serum concentration of Muraglitazar can be increased when it is combined with Abiraterone.
AmitriptylineThe metabolism of Muraglitazar can be decreased when combined with Amitriptyline.
BexaroteneThe metabolism of Muraglitazar can be decreased when combined with Bexarotene.
CarbamazepineThe serum concentration of Muraglitazar can be decreased when it is combined with Carbamazepine.
CelecoxibThe metabolism of Muraglitazar can be decreased when combined with Celecoxib.
CholecalciferolThe metabolism of Muraglitazar can be decreased when combined with Cholecalciferol.
CrisaboroleThe metabolism of Muraglitazar can be decreased when combined with Crisaborole.
CurcuminThe metabolism of Muraglitazar can be decreased when combined with Curcumin.
DabrafenibThe serum concentration of Muraglitazar can be decreased when it is combined with Dabrafenib.
DeferasiroxThe serum concentration of Muraglitazar can be increased when it is combined with Deferasirox.
Food Interactions
Not Available

References

General References
Not Available
External Links
ChemSpider
178524
BindingDB
50150998
ChEMBL
CHEMBL186179
Wikipedia
Muraglitazar

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2, 3CompletedTreatmentDiabetes Mellitus II1
2, 3CompletedTreatmentDyslipidemias1
3CompletedTreatmentDiabetes Mellitus (DM)1
3CompletedTreatmentMetabolics Diabetes Nos1
3CompletedTreatmentType 2 Diabetes Mellitus5
3TerminatedTreatmentType 2 Diabetes Mellitus1

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/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

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
Phenyl-1,3-oxazole / Alpha-amino acid or derivatives / 2,4,5-trisubstituted 1,3-oxazole / Phenoxy compound / Anisole / Phenol ether / Methoxybenzene / Alkyl aryl ether / Monocyclic benzene moiety / Benzenoid
show 18 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
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
Human
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
Human
Pharmacological action
Unknown
Actions
Substrate
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. [PubMed:17062778]
Kind
Protein
Organism
Human
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. [PubMed:17898154]
Kind
Protein
Organism
Human
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. [PubMed:17898154]
  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. [PubMed:17062778]
Kind
Protein
Organism
Human
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. [PubMed:17062778]

Drug created on March 19, 2008 10:35 / Updated on August 02, 2018 05:37