TESAGLITAZAR

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C20H24O7S
Molecular Weight	408.465
Optical Activity	UNSPECIFIED
Defined Stereocenters	1 / 1
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCO[C@@H](CC1=CC=C(OCCC2=CC=C(OS(C)(=O)=O)C=C2)C=C1)C(O)=O

InChI

InChIKey=CXGTZJYQWSUFET-IBGZPJMESA-N

InChI=1S/C20H24O7S/c1-3-25-19(20(21)22)14-16-6-8-17(9-7-16)26-13-12-15-4-10-18(11-5-15)27-28(2,23)24/h4-11,19H,3,12-14H2,1-2H3,(H,21,22)/t19-/m0/s1

HIDE SMILES / InChI

Molecular Formula	C20H24O7S
Molecular Weight	408.465
Charge	0
Count

Stereochemistry	ABSOLUTE
Additional Stereochemistry	No
Defined Stereocenters	1 / 1
E/Z Centers	0
Optical Activity	UNSPECIFIED

Description
Sources: http://www.ncbi.nlm.nih.gov/pubmed/16628256
Curator's Comment: description was created based on several sources, including http://www.docguide.com/astrazeneca-discontinues-development-galida-tesaglitazar

Tesaglitazar, a dihydro cinnamate derivative (AZ 242), is a dual agonist of PPARα and γ that demonstrates IC50 values of 1 and 0.2 µM, respectively. It has been investigated its potential to address disorders in glucose and lipid metabolism in patients with type 2 diabetes. The drug had completed several phase III clinical trials, however in May, 2006 AstraZeneca announced that it had discontinued further development. Following analysis and interpretation of recently obtained results from the first four of eight phase 3 clinical trials (GALLANT 6,7,8 and 9) and one phase 2 trial (ARMOR), which were reviewed in consultation with external experts, the company considers that the overall benefit/risk profile is unlikely to offer patients significant advantage over currently available therapy. Central to the decision is data showing elevations in serum creatinine and an associated decrease in glomerular filtration rate (GFR). The magnitude of the serum creatinine elevation was greater than anticipated based on earlier clinical studies. Such elevations reversed towards baseline upon stopping treatment with the drug and have not been associated with kidney toxicity.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Peroxisome proliferator-activated receptor gamma 109 Target ID: CHEMBL235 Sources: http://www.ncbi.nlm.nih.gov/pubmed/11587644	Agonist 2662		0.2 µM [IC50]
Peroxisome proliferator-activated receptor alpha 62 Target ID: CHEMBL239 Sources: http://www.ncbi.nlm.nih.gov/pubmed/11587644	Agonist 2662		1.0 µM [IC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Type 2 diabetes mellitus 256 Sources: http://www.ncbi.nlm.nih.gov/pubmed/16628256	Primary		Phase III 663	GALIDA Approved Use Unknown
Metabolic syndrome 32 Sources: http://www.ncbi.nlm.nih.gov/pubmed/19887847	Primary		Phase III 663	GALIDA Approved Use Unknown

PubMed

Title	Date	PubMed
AZ 242, a novel PPARalpha/gamma agonist with beneficial effects on insulin resistance and carbohydrate and lipid metabolism in ob/ob mice and obese Zucker rats.	2002 Nov	12401884
Tesaglitazar AstraZeneca.	2002 Sep	12800054
Factorial design for the development of automated solid-phase extraction in the 96-well format for determination of tesaglitazar, in plasma, by liquid chromatography-mass spectrometry.	2003 Apr 25	12650747
Gateways to clinical trials.	2003 Nov	14685303
Gateways to clinical trials.	2003 Oct	14671684
Peroxisome proliferator-activated receptor (PPAR) activation induces tissue-specific effects on fatty acid uptake and metabolism in vivo--a study using the novel PPARalpha/gamma agonist tesaglitazar.	2004 Jul	15059948
Tesaglitazar.	2005 Nov	16254788
Tesaglitazar, a dual PPAR{alpha}/{gamma} agonist, ameliorates glucose and lipid intolerance in obese Zucker rats.	2005 Oct	16183630
Tesaglitazar, a novel dual peroxisome proliferator-activated receptor alpha/gamma agonist, dose-dependently improves the metabolic abnormalities associated with insulin resistance in a non-diabetic population.	2005 Sep	16001233
Dual and pan-peroxisome proliferator-activated receptors (PPAR) co-agonism: the bezafibrate lessons.	2005 Sep 16	16168052
Effect of tesaglitazar, a dual PPAR alpha/gamma agonist, on glucose and lipid abnormalities in patients with type 2 diabetes: a 12-week dose-ranging trial.	2006 Dec	17166340
Gateways to clinical trials.	2006 May	16801985
Food does not affect the pharmacokinetics of tesaglitazar, a novel dual peroxisome proliferator-activated receptor alpha/gamma agonist.	2006 Sep	16920896
Quinoline-based derivatives of pirinixic acid as dual PPAR alpha/gamma agonists.	2007 Jul	17610302
Tesaglitazar, a PPARalpha/gamma agonist, induces interstitial mesenchymal cell DNA synthesis and fibrosarcomas in subcutaneous tissues in rats.	2007 Jul	17468185
Tesaglitazar, a dual peroxisome proliferator-activated receptor alpha/gamma agonist, reduces atherosclerosis in female low density lipoprotein receptor deficient mice.	2007 Nov	17214992
Tesaglitazar, as add-on therapy to sulphonylurea, dose-dependently improves glucose and lipid abnormalities in patients with type 2 diabetes.	2007 Sep	17907109
A double-blind, randomised trial of tesaglitazar versus pioglitazone in patients with type 2 diabetes mellitus.	2007 Sep	17907108
Improvement of postprandial lipid handling and glucose tolerance in a non-diabetic population by the dual PPARalpha/gamma agonist, tesaglitazar.	2007 Sep	17907107
Learning from tesaglitazar.	2007 Sep	17907105
The dual peroxisome proliferator-activated receptor alpha/gamma agonist tesaglitazar further improves the lipid profile in dyslipidemic subjects treated with atorvastatin.	2007 Sep	17697874
Mild electrical stimulation with heat shock ameliorates insulin resistance via enhanced insulin signaling.	2008	19114996
Should We Use PPAR Agonists to Reduce Cardiovascular Risk?	2008	18288293
PPAR Agonists and Cardiovascular Disease in Diabetes.	2008	18288280
Models for plasma glucose, HbA1c, and hemoglobin interrelationships in patients with type 2 diabetes following tesaglitazar treatment.	2008 Aug	18388881
Mechanistic modelling of tesaglitazar pharmacokinetic data in subjects with various degrees of renal function--evidence of interconversion.	2008 Jun	18294322
Design, synthesis, and biological evaluation of novel constrained meta-substituted phenyl propanoic acids as peroxisome proliferator-activated receptor alpha and gamma dual agonists.	2008 Oct 23	18826205
A model for glucose, insulin, and beta-cell dynamics in subjects with insulin resistance and patients with type 2 diabetes.	2010 Aug	20484615
PPAR agonists reduce steatosis in oleic acid-overloaded HepaRG cells.	2014 Apr 1	24534255

Patents

Sample Use Guides

In Vivo Use Guide

concentration of drug was used: 0.1, 0.25, 0.5 and 1.0 mg/day

Route of Administration: Oral

In Vitro Use Guide

The effects of various PPAR agonists, i.e. fenofibrate, tesaglitazar etc on oleic acid-induced steatotic HepaRG cells were investigated after a single 24-hour or 2-week repeat treatment. Lipid vesicles stained by Oil-Red O and triglycerides accumulation caused by oleic acid overload, were decreased, by up to 50%, while fatty acid oxidation was induced after 2-week co-treatment with PPAR agonists

Substance Class	Chemical Created by `admin` on `Wed Jul 05 23:50:41 UTC 2023` Edited by `admin` on `Wed Jul 05 23:50:41 UTC 2023`
Record UNII	6734037O3L
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TESAGLITAZAR

Official Name

English

GALIDA

Brand Name

English

AR-H-039242

Code

English

TESAGLITAZAR [USAN]

Common Name

English

BENZENEPROPANOIC ACID,.ALPHA.-ETHOXY-4-(2-(4-((METHYLSULFONYL)OXY)PHENYL)ETHOXY) ,(.ALPHA.S)-

Systematic Name

English

Tesaglitazar [WHO-DD]

Common Name

English

TESAGLITAZAR [MI]

Common Name

English

TESAGLITAZAR [JAN]

Common Name

English

AZ-242

Code

English

AR-H039242XX

Code

English

(2S)-2-Ethoxy-3-[4-[2-[4-[(methylsulfonyl)oxy]phenyl]ethoxy]phenyl]propanoic acid

Systematic Name

English

tesaglitazar [INN]

Common Name

English

BR-44608

Code

English

(S)-2-ETHOXY-3-(4-(2-(4-METHYLSULFONYLOXYPHENYL)ETHOXY)PHENYL)PROPANOIC ACID

Systematic Name

English

Classification Tree Code System Code

NCI_THESAURUS

C98233