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
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
| 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 |
DescriptionCurator's Comment: description was created based on several sources, including
http://www.docguide.com/astrazeneca-discontinues-development-galida-tesaglitazar
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
PubMed
| Title | Date | PubMed |
|---|---|---|
| Tesaglitazar AstraZeneca. | 2002 Sep |
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| 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 |
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| Gateways to clinical trials. | 2003 Oct |
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| Tesaglitazar, a dual PPAR{alpha}/{gamma} agonist, ameliorates glucose and lipid intolerance in obese Zucker rats. | 2005 Oct |
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| 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 |
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| 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 |
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| Therapeutic options in development for management of diabetes: pharmacologic agents and new technologies. | 2006 Jan-Feb |
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| Tesaglitazar: a promising approach in type 2 diabetes. | 2006 Mar |
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| Gateways to clinical trials. | 2006 May |
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| Dual PPARalpha/gamma agonist tesaglitazar reduces atherosclerosis in insulin-resistant and hypercholesterolemic ApoE*3Leiden mice. | 2006 Nov |
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| Tesaglitazar, a dual peroxisome proliferator-activated receptor alpha/gamma agonist, reduces atherosclerosis in female low density lipoprotein receptor deficient mice. | 2007 Nov |
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| Improvement of postprandial lipid handling and glucose tolerance in a non-diabetic population by the dual PPARalpha/gamma agonist, tesaglitazar. | 2007 Sep |
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| The dual peroxisome proliferator-activated receptor alpha/gamma agonist tesaglitazar further improves the lipid profile in dyslipidemic subjects treated with atorvastatin. | 2007 Sep |
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| Mild electrical stimulation with heat shock ameliorates insulin resistance via enhanced insulin signaling. | 2008 |
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| PPARgamma and Agonists against Cancer: Rational Design of Complementation Treatments. | 2008 |
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| Peroxisome Proliferators-Activated Receptor (PPAR) Modulators and Metabolic Disorders. | 2008 |
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| Should We Use PPAR Agonists to Reduce Cardiovascular Risk? | 2008 |
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| PPAR Agonists and Cardiovascular Disease in Diabetes. | 2008 |
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| Models for plasma glucose, HbA1c, and hemoglobin interrelationships in patients with type 2 diabetes following tesaglitazar treatment. | 2008 Aug |
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| Mechanistic modelling of tesaglitazar pharmacokinetic data in subjects with various degrees of renal function--evidence of interconversion. | 2008 Jun |
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| 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 |
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| The dual PPARalpha/gamma agonist tesaglitazar blocks progression of pre-existing atherosclerosis in APOE*3Leiden.CETP transgenic mice. | 2009 Apr |
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| Gene Expression Changes Induced by PPAR Gamma Agonists in Animal and Human Liver. | 2010 |
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| A model for glucose, insulin, and beta-cell dynamics in subjects with insulin resistance and patients with type 2 diabetes. | 2010 Aug |
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| Successful drug development despite adverse preclinical findings part 2: examples. | 2010 Dec |
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| Proliferative and molecular effects of the dual PPARalpha/gamma agonist tesaglitazar in rat adipose tissues: relevance for induction of fibrosarcoma. | 2011 Feb |
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| Tesaglitazar, a dual PPAR-α/γ agonist, hamster carcinogenicity, investigative animal and clinical studies. | 2012 |
|
| PPAR agonists reduce steatosis in oleic acid-overloaded HepaRG cells. | 2014 Apr 1 |
Sample Use Guides
concentration of drug was used: 0.1, 0.25, 0.5 and 1.0 mg/day
Route of Administration:
Oral
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
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admin
on
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Fri Dec 15 16:24:21 UTC 2023
by
admin
on
Fri Dec 15 16:24:21 UTC 2023
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| Record UNII |
6734037O3L
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| Record Status |
Validated (UNII)
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C98233
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8092
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m1262
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C75985
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6734037O3L
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C501413
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TESAGLITAZAR
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SUB25217
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CHEMBL282686
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EXCRETED UNCHANGED |
URINE
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TARGET -> AGONIST |
Tesaglitazar is a novel dual-acting peroxisome proliferator-activated receptor alpha and gamma agonist.
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TARGET -> AGONIST |
Tesaglitazar is a novel dual-acting peroxisome proliferator-activated receptor alpha and gamma agonist.
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ACTIVE MOIETY |
| Name | Property Type | Amount | Referenced Substance | Defining | Parameters | References |
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| Biological Half-life | PHARMACOKINETIC |
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| Volume of Distribution | PHARMACOKINETIC |
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| Tmax | PHARMACOKINETIC |
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