MURAGLITAZAR

Details

Stereochemistry	ACHIRAL
Molecular Formula	C29H28N2O7
Molecular Weight	516.5418
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

COC1=CC=C(OC(=O)N(CC(O)=O)CC2=CC=C(OCCC3=C(C)OC(=N3)C4=CC=CC=C4)C=C2)C=C1

InChI

InChIKey=IRLWJILLXJGJTD-UHFFFAOYSA-N

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)

HIDE SMILES / InChI

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/20368213 | https://www.ncbi.nlm.nih.gov/pubmed/15771468

Muraglitazar previously known as BMS-298585 has been identified as a non-thiazolidinedione dual agonist of peroxisome proliferator-activated receptor alpha/gamma. Muraglitazar is currently in clinical trial phase III development for the treatment of type 2 diabetes and dyslipidemia.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Peroxisome proliferator-activated receptor alpha 62 Target ID: CHEMBL239 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15771468	Agonist 2678		320.0 nM [EC50]
Peroxisome proliferator-activated receptor gamma 111 Target ID: CHEMBL235 Sources: https://www.ncbi.nlm.nih.gov/pubmed/15771468	Agonist 2678		110.0 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Type 2 diabetes mellitus 259 Sources: https://clinicaltrials.gov/ct2/show/NCT00240383	Primary		Phase III 656	Unknown Approved Use Unknown
Dyslipidemia 30 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16341289	Primary		Phase III 656	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
1.8 μg/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17062777	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		MURAGLITAZAR plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
12 μg × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17062777	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		MURAGLITAZAR plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
35.1 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/17062777	10 mg single, oral dose: 10 mg route of administration: Oral experiment type: SINGLE co-administered:		MURAGLITAZAR plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Sourcing

Vendor/Aggregator	ID	URL
1PlusChem LLC	1P007HMK	https://www.1pchem.com/search?query=1P007HMK
Angene	AGN-PC-04XYUX	http://www.angenechemical.com/productshow/AGN-PC-04XYUX.html
ApexBio Technology	C3986	https://www.apexbt.com/catalogsearch/result/?q=C3986
Cayman Chemical	10007853	http://www.caymanchem.com/app/template/Product.vm/catalog/10007853
MolPort	MolPort-006-395-259	https://www.molport.com/shop/molecule-link/MolPort-006-395-259
MuseChem	R009405	https://www.musechem.com/product/R009405.html
Toronto Research Chemicals	M796500	https://www.trc-canada.com/product-detail/?CatNum=M796500
Toronto Research Chemicals	S687350	https://www.trc-canada.com/product-detail/?CatNum=S687350
Wonderchem	WD05WNG	http://www.wonder-chem.com/search.html?text=WD05WNG
eMolecules	10595085	https://orderbb.emolecules.com/search/#?query=10595085
mcule	MCULE-5270352456	https://mcule.com/MCULE-5270352456/

PubMed

Title	Date	PubMed
Gateways to clinical trials.	2004 Sep	15538546
Muraglitazar (Bristol-Myers Squibb/Merck).	2005 Apr	15898350
Muraglitazar, a dual (alpha/gamma) PPAR activator: a randomized, double-blind, placebo-controlled, 24-week monotherapy trial in adult patients with type 2 diabetes.	2005 Aug	16199244
Meeting highlights. 65th annual scientific sessions of the American Diabetes Association, San Diego. Dual PPAR agonist improves glycemic control, lipids in type 2 diabetes.	2005 Aug	16104078
American Diabetes Association - 65th Scientific Sessions. PPAR agents.	2005 Aug	16044361
Design and synthesis of N-[(4-methoxyphenoxy)carbonyl]-N-[[4-[2-(5- methyl-2-phenyl-4-oxazolyl)ethoxy]phenyl]methyl]glycine [Muraglitazar/BMS-298585], a novel peroxisome proliferator-activated receptor alpha/gamma dual agonist with efficacious glucose and lipid-lowering activities.	2005 Mar 24	15771468
Molecule of the month. Muraglitazar.	2005 May	16034485
Selling safety--lessons from muraglitazar.	2005 Nov 23	16239638
K-111: the emerging evidence for its potential in the treatment of the metabolic syndrome.	2006	22500152
A bumpy road to breakthroughs. The news: it's hard to beat today's cardiac treatments.	2006 Feb	17763560
A 96-well single-pot protein precipitation, liquid chromatography/tandem mass spectrometry (LC/MS/MS) method for the determination of muraglitazar, a novel diabetes drug, in human plasma.	2006 Feb 2	16388995
Gateways to clinical trials.	2006 Jun	16845450
[Dipeptidylpeptidase IV inhibitors and dual action PPAR-agonists].	2006 Mar	16550882
Drug safety system needs overhaul, experts say.	2006 Mar 15	16537829
Adverse events related to muraglitazar use in diabetes.	2006 May 3	16670403
Treatment update: thiazolidinediones in combination with metformin for the treatment of type 2 diabetes.	2007	17969380
The dual peroxisome proliferator-activated receptor alpha/gamma activator muraglitazar prevents the natural progression of diabetes in db/db mice.	2007 Apr	17259449
Subchronic urinary bladder effects of muraglitazar in male rats.	2007 Mar	17132713
The integration of lipid-sensing and anti-inflammatory effects: how the PPARs play a role in metabolic balance.	2007 May 25	17531095
Urine acidification has no effect on peroxisome proliferator-activated receptor (PPAR) signaling or epidermal growth factor (EGF) expression in rat urinary bladder urothelium.	2007 Sep 15	17663016
The Development of INT131 as a Selective PPARgamma Modulator: Approach to a Safer Insulin Sensitizer.	2008	18769500
Peroxisome Proliferators-Activated Receptor (PPAR) Modulators and Metabolic Disorders.	2008	18566691
Genetic and gene expression studies implicate renin and endothelin-1 in edema caused by peroxisome proliferator-activated receptor gamma agonists.	2008 Oct	18794727
PPAR agonists reduce steatosis in oleic acid-overloaded HepaRG cells.	2014 Apr 1	24534255

Patents

Sample Use Guides

In Vivo Use Guide

This was a randomized, double-blind, placebo-controlled, parallel-group, multicenter, 24-week monotherapy study in drug-naive, type 2 diabetes patients with inadequate glycemic control. Men and women aged 18 to 70 years with a body mass index < or =41 kg/m(2) and serum triglyceride levels < or =600 mg/dL were eligible for study participation. The study included double-blind and open-label treatment phases. Patients with glycosylated hemoglobin (HbA(1c)) levels > or =7.0% and < or =10.0% at screening were enrolled in the double-blind treatment phase. These patients received treatment with muraglitazar 2.5 mg, muraglitazar 5 mg, or placebo.

Route of Administration: Oral

In Vitro Use Guide

Muraglitazar/BMS-298585 (2) has been identified as a non-thiazolidinedione PPAR alpha/gamma dual agonist that shows potent activity in vitro at human PPARalpha (EC(50) = 320 nM) and PPARgamma(EC(50) = 110 nM).

Name

Type

Language

MURAGLITAZAR

Official Name

English

MURAGLITAZAR [USAN]

Common Name

English

BMS-298585

Code

English

MURAGLITAZAR [MART.]

Common Name

English

muraglitazar [INN]

Common Name

English

[[(4-Methoxyphenoxy)carbonyl][4-[2-(5-methyl-2-phenyloxazol-4-yl)ethoxy]benzyl]amino]acetic acid

Systematic Name

English

BMS-298585-01

Code

English

N-((4-METHOXYPHENOXY)CARBONYL)-N-((4-(2-(5-METHYL-2-PHENYL-4-OXAZOLYL)ETHOXY)PHENYL)-METHYL)GLYCINE

Systematic Name

English

MURAGLITAZAR [MI]

Common Name

English

GLYCINE, N-((4-METHOXYPHENOXY)CARBONYL)-N-((4-(2-(5-METHYL-2-PHENYL-4-OXAZOLYL)ETHOXY)PHENYL)METHYL)-

Systematic Name

English

Muraglitazar [WHO-DD]

Common Name

English

MK-0478

Code

English

MK0478

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C98233