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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 of TESAGLITAZAR

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

Description
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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.2 µM [IC50]
1.0 µM [IC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
GALIDA

Approved Use

Unknown
Primary
GALIDA

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
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
Gateways to clinical trials.
2003 Nov
Gateways to clinical trials.
2003 Oct
Pharmacokinetics and metabolism of tesaglitazar, a novel dual-acting peroxisome proliferator-activated receptor alpha/gamma agonist, after a single oral and intravenous dose in humans.
2004 Sep
Tesaglitazar.
2005 Nov
Food does not affect the pharmacokinetics of tesaglitazar, a novel dual peroxisome proliferator-activated receptor alpha/gamma agonist.
2006 Sep
PPAR dual agonists: are they opening Pandora's Box?
2007 Aug
Tesaglitazar, a PPARalpha/gamma agonist, induces interstitial mesenchymal cell DNA synthesis and fibrosarcomas in subcutaneous tissues in rats.
2007 Jul
Tesaglitazar, a dual peroxisome proliferator-activated receptor alpha/gamma agonist, reduces atherosclerosis in female low density lipoprotein receptor deficient mice.
2007 Nov
Improvement of postprandial lipid handling and glucose tolerance in a non-diabetic population by the dual PPARalpha/gamma agonist, tesaglitazar.
2007 Sep
Learning from tesaglitazar.
2007 Sep
The dual peroxisome proliferator-activated receptor alpha/gamma agonist tesaglitazar further improves the lipid profile in dyslipidemic subjects treated with atorvastatin.
2007 Sep
PPARgamma and Agonists against Cancer: Rational Design of Complementation Treatments.
2008
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
The dual PPARalpha/gamma agonist tesaglitazar blocks progression of pre-existing atherosclerosis in APOE*3Leiden.CETP transgenic mice.
2009 Apr
Tesaglitazar, a dual peroxisome proliferator-activated receptor agonist (PPAR alpha/gamma), improves metabolic abnormalities and reduces renal injury in obese Zucker rats.
2010
Proliferative and molecular effects of the dual PPARalpha/gamma agonist tesaglitazar in rat adipose tissues: relevance for induction of fibrosarcoma.
2011 Feb
Tesaglitazar, a dual PPAR-α/γ agonist, hamster carcinogenicity, investigative animal and clinical studies.
2012
Patents

Sample Use Guides

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
Name Type Language
TESAGLITAZAR
INN   JAN   MI   USAN   WHO-DD  
INN   USAN  
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
Created by admin on Fri Dec 15 16:24:21 GMT 2023 , Edited by admin on Fri Dec 15 16:24:21 GMT 2023
Code System Code Type Description
INN
8092
Created by admin on Fri Dec 15 16:24:21 GMT 2023 , Edited by admin on Fri Dec 15 16:24:21 GMT 2023
PRIMARY
MERCK INDEX
m1262
Created by admin on Fri Dec 15 16:24:21 GMT 2023 , Edited by admin on Fri Dec 15 16:24:21 GMT 2023
PRIMARY Merck Index
EPA CompTox
DTXSID4048773
Created by admin on Fri Dec 15 16:24:21 GMT 2023 , Edited by admin on Fri Dec 15 16:24:21 GMT 2023
PRIMARY
NCI_THESAURUS
C75985
Created by admin on Fri Dec 15 16:24:21 GMT 2023 , Edited by admin on Fri Dec 15 16:24:21 GMT 2023
PRIMARY
FDA UNII
6734037O3L
Created by admin on Fri Dec 15 16:24:21 GMT 2023 , Edited by admin on Fri Dec 15 16:24:21 GMT 2023
PRIMARY
MESH
C501413
Created by admin on Fri Dec 15 16:24:21 GMT 2023 , Edited by admin on Fri Dec 15 16:24:21 GMT 2023
PRIMARY
WIKIPEDIA
TESAGLITAZAR
Created by admin on Fri Dec 15 16:24:21 GMT 2023 , Edited by admin on Fri Dec 15 16:24:21 GMT 2023
PRIMARY
CAS
251565-85-2
Created by admin on Fri Dec 15 16:24:21 GMT 2023 , Edited by admin on Fri Dec 15 16:24:21 GMT 2023
PRIMARY
DRUG BANK
DB06536
Created by admin on Fri Dec 15 16:24:21 GMT 2023 , Edited by admin on Fri Dec 15 16:24:21 GMT 2023
PRIMARY
PUBCHEM
208901
Created by admin on Fri Dec 15 16:24:21 GMT 2023 , Edited by admin on Fri Dec 15 16:24:21 GMT 2023
PRIMARY
USAN
QQ-51
Created by admin on Fri Dec 15 16:24:21 GMT 2023 , Edited by admin on Fri Dec 15 16:24:21 GMT 2023
PRIMARY
SMS_ID
100000089231
Created by admin on Fri Dec 15 16:24:21 GMT 2023 , Edited by admin on Fri Dec 15 16:24:21 GMT 2023
PRIMARY
EVMPD
SUB25217
Created by admin on Fri Dec 15 16:24:21 GMT 2023 , Edited by admin on Fri Dec 15 16:24:21 GMT 2023
PRIMARY
ChEMBL
CHEMBL282686
Created by admin on Fri Dec 15 16:24:21 GMT 2023 , Edited by admin on Fri Dec 15 16:24:21 GMT 2023
PRIMARY