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
DescriptionSources: http://www.ncbi.nlm.nih.gov/pubmed/16628256Curator's Comment: description was created based on several sources, including
http://www.docguide.com/astrazeneca-discontinues-development-galida-tesaglitazar
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 |
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Target ID: CHEMBL235 Sources: http://www.ncbi.nlm.nih.gov/pubmed/11587644 |
0.2 µM [IC50] | ||
Target ID: CHEMBL239 Sources: http://www.ncbi.nlm.nih.gov/pubmed/11587644 |
1.0 µM [IC50] |
Conditions
Condition | Modality | Targets | Highest Phase | Product |
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Primary | GALIDA Approved UseUnknown |
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Primary | GALIDA Approved UseUnknown |
PubMed
Title | Date | PubMed |
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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 |
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Gateways to clinical trials. | 2003 Nov |
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Gateways to clinical trials. | 2003 Oct |
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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 |
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Tesaglitazar. | 2005 Nov |
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Food does not affect the pharmacokinetics of tesaglitazar, a novel dual peroxisome proliferator-activated receptor alpha/gamma agonist. | 2006 Sep |
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PPAR dual agonists: are they opening Pandora's Box? | 2007 Aug |
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Tesaglitazar, a PPARalpha/gamma agonist, induces interstitial mesenchymal cell DNA synthesis and fibrosarcomas in subcutaneous tissues in rats. | 2007 Jul |
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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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Learning from 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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PPARgamma and Agonists against Cancer: Rational Design of Complementation Treatments. | 2008 |
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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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Tesaglitazar, a dual peroxisome proliferator-activated receptor agonist (PPAR alpha/gamma), improves metabolic abnormalities and reduces renal injury in obese Zucker rats. | 2010 |
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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 |
Sample Use Guides
In Vivo Use Guide
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16001233
concentration of drug was used: 0.1, 0.25, 0.5 and 1.0 mg/day
Route of Administration:
Oral
In Vitro Use Guide
Sources: http://www.ncbi.nlm.nih.gov/pubmed/24534255
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
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C98233
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