Tesaglitazar

This drug entry is a stub and has not been fully annotated. It is scheduled to be annotated soon.

Identification

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Name
Tesaglitazar
Accession Number
DB06536  (DB07399)
Type
Small Molecule
Groups
Investigational
Description

Tesaglitazar is a dual peroxisome proliferator-activated receptor alpha/gamma agonist which improves apolipoprotein levels in non-diabetic subjects with insulin resistance. Tesaglitazar is a proposed treatment for type 2 diabetes and has completed several phase III clinical trials, however in May 2006 AstraZeneca announced that they had discontinued further development.

Structure
Thumb
Synonyms
Not Available
External IDs
AR-H-039242 / AR-H039242XX / AZ-242 / BR-44608
International/Other Brands
Galida (AstraZeneca)
Categories
UNII
6734037O3L
CAS number
251565-85-2
Weight
Average: 408.465
Monoisotopic: 408.124273812
Chemical Formula
C20H24O7S
InChI Key
CXGTZJYQWSUFET-IBGZPJMESA-N
InChI
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
IUPAC Name
(2S)-2-ethoxy-3-(4-{2-[4-(methanesulfonyloxy)phenyl]ethoxy}phenyl)propanoic acid
SMILES
CCO[C@@H](CC1=CC=C(OCCC2=CC=C(OS(C)(=O)=O)C=C2)C=C1)C(O)=O

Pharmacology

Indication

Investigated for use/treatment in diabetes mellitus type 2.

Pharmacodynamics

Treatment with tesaglitazar lowered fasting plasma glucose, improved glucose tolerance, substantially reduced fasting and postload insulin levels, and markedly lowered fasting TG and improved lipid tolerance.

Mechanism of action
TargetActionsOrganism
UPeroxisome proliferator-activated receptor alphaNot AvailableHumans
UPeroxisome proliferator-activated receptor gammaNot AvailableHumans
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
Not Available
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
  1. Oakes ND, Thalen P, Hultstrand T, Jacinto S, Camejo G, Wallin B, Ljung B: Tesaglitazar, a dual PPAR{alpha}/{gamma} agonist, ameliorates glucose and lipid intolerance in obese Zucker rats. Am J Physiol Regul Integr Comp Physiol. 2005 Oct;289(4):R938-46. [PubMed:16183630]
  2. Schuster H, Fagerberg B, Edwards S, Halmos T, Lopatynski J, Stender S, Birketvedt GS, Tonstad S, Gause-Nilsson I, Halldorsdottir S, Ohman KP: Tesaglitazar, a dual peroxisome proliferator-activated receptor alpha/gamma agonist, improves apolipoprotein levels in non-diabetic subjects with insulin resistance. Atherosclerosis. 2008 Mar;197(1):355-62. Epub 2007 Jul 13. [PubMed:17631296]
External Links
PubChem Compound
208901
ChemSpider
180999
BindingDB
28798
ChEMBL
CHEMBL282686
HET
AZ2
Wikipedia
Tesaglitazar
PDB Entries
1i7g / 1i7i

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentType 2 Diabetes Mellitus1
2TerminatedNot AvailableType 2 Diabetes Mellitus1
2TerminatedTreatmentType 2 Diabetes Mellitus2
3TerminatedTreatmentType 2 Diabetes Mellitus11

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.00351 mg/mLALOGPS
logP3.18ALOGPS
logP3.14ChemAxon
logS-5.1ALOGPS
pKa (Strongest Acidic)3.73ChemAxon
pKa (Strongest Basic)-4.1ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area99.13 Å2ChemAxon
Rotatable Bond Count11ChemAxon
Refractivity103.52 m3·mol-1ChemAxon
Polarizability42.56 Å3ChemAxon
Number of Rings2ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9156
Blood Brain Barrier+0.8918
Caco-2 permeable-0.6095
P-glycoprotein substrateNon-substrate0.5288
P-glycoprotein inhibitor IInhibitor0.5859
P-glycoprotein inhibitor IINon-inhibitor0.9059
Renal organic cation transporterNon-inhibitor0.7945
CYP450 2C9 substrateNon-substrate0.813
CYP450 2D6 substrateNon-substrate0.8296
CYP450 3A4 substrateSubstrate0.598
CYP450 1A2 substrateNon-inhibitor0.7271
CYP450 2C9 inhibitorNon-inhibitor0.7522
CYP450 2D6 inhibitorNon-inhibitor0.8978
CYP450 2C19 inhibitorNon-inhibitor0.6884
CYP450 3A4 inhibitorNon-inhibitor0.9581
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8034
Ames testAMES toxic0.5309
CarcinogenicityCarcinogens 0.5139
BiodegradationNot ready biodegradable0.6566
Rat acute toxicity2.1971 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.7874
hERG inhibition (predictor II)Inhibitor0.5843
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as phenylpropanoic acids. These are compounds with a structure containing a benzene ring conjugated to a propanoic acid.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Phenylpropanoic acids
Sub Class
Not Available
Direct Parent
Phenylpropanoic acids
Alternative Parents
Tyrosols and derivatives / Phenoxy compounds / Phenol ethers / Alkyl aryl ethers / Sulfonic acid esters / Organosulfonic acid esters / Sulfonyls / Methanesulfonates / Monocarboxylic acids and derivatives / Dialkyl ethers
show 4 more
Substituents
3-phenylpropanoic-acid / Tyrosol derivative / Phenoxy compound / Phenol ether / Alkyl aryl ether / Monocyclic benzene moiety / Benzenoid / Organosulfonic acid ester / Sulfonic acid ester / Methanesulfonate
show 15 more
Molecular Framework
Aromatic homomonocyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Ligand-activated transcription factor. Key regulator of lipid metabolism. Activated by the endogenous ligand 1-palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine (16:0/18:1-GPC). Activated by oleyleth...
Gene Name
PPARA
Uniprot ID
Q07869
Uniprot Name
Peroxisome proliferator-activated receptor alpha
Molecular Weight
52224.595 Da
References
  1. Tenenbaum A, Motro M, Fisman EZ: Dual and pan-peroxisome proliferator-activated receptors (PPAR) co-agonism: the bezafibrate lessons. Cardiovasc Diabetol. 2005 Sep 16;4:14. [PubMed:16168052]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
General Function
Zinc ion binding
Specific Function
Nuclear receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Once activated by a ligand, the nuclear receptor binds to DNA specific PPAR response elements (PPRE...
Gene Name
PPARG
Uniprot ID
P37231
Uniprot Name
Peroxisome proliferator-activated receptor gamma
Molecular Weight
57619.58 Da
References
  1. Tenenbaum A, Motro M, Fisman EZ: Dual and pan-peroxisome proliferator-activated receptors (PPAR) co-agonism: the bezafibrate lessons. Cardiovasc Diabetol. 2005 Sep 16;4:14. [PubMed:16168052]

Drug created on March 19, 2008 10:36 / Updated on June 04, 2019 06:25