Identification

Name
Cardarine
Accession Number
DB05416  (DB13015)
Type
Small Molecule
Groups
Investigational
Description

Cardarine (GW-501516) is a peroxisome proliferator-activator receptor-delta agonist for the potential treatment of dyslipidemia. Cardarine has been investigated for the treatment of Obesity, Lipid Disorders, and Cardiovascular Disease.

Structure
Thumb
Synonyms
Not Available
External IDs
GSK-516 / GW-1516 / GW-501516 / GW501516
Categories
UNII
7I2HA1NU22
CAS number
317318-70-0
Weight
Average: 453.498
Monoisotopic: 453.068019442
Chemical Formula
C21H18F3NO3S2
InChI Key
YDBLKRPLXZNVNB-UHFFFAOYSA-N
InChI
InChI=1S/C21H18F3NO3S2/c1-12-9-16(7-8-17(12)28-10-19(26)27)29-11-18-13(2)25-20(30-18)14-3-5-15(6-4-14)21(22,23)24/h3-9H,10-11H2,1-2H3,(H,26,27)
IUPAC Name
2-{2-methyl-4-[({4-methyl-2-[4-(trifluoromethyl)phenyl]-1,3-thiazol-5-yl}methyl)sulfanyl]phenoxy}acetic acid
SMILES
CC1=C(CSC2=CC(C)=C(OCC(O)=O)C=C2)SC(=N1)C1=CC=C(C=C1)C(F)(F)F

Pharmacology

Indication

Investigated for use/treatment in hyperlipidemia.

Pharmacodynamics
Not Available
Mechanism of action

This drug regulates fatty acid oxidation in several tissues, such as skeletal muscle and adipose tissue. Overexpression of PPARdelta using a transgenic murine model promotes an increase of muscle oxidative capability. It also plays a major role in the metabolic adaptations to western diet characterized by an excessive amount of saturated fat.

TargetActionsOrganism
UPeroxisome proliferator-activated receptor delta
agonist
Human
UPeroxisome proliferator-activated receptor alpha
agonist
Human
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. Dimopoulos N, Watson M, Green C, Hundal HS: The PPARdelta agonist, GW501516, promotes fatty acid oxidation but has no direct effect on glucose utilisation or insulin sensitivity in rat L6 skeletal muscle cells. FEBS Lett. 2007 Oct 2;581(24):4743-8. Epub 2007 Sep 6. [PubMed:17869249]
  2. Kramer DK, Al-Khalili L, Guigas B, Leng Y, Garcia-Roves PM, Krook A: Role of AMP kinase and PPARdelta in the regulation of lipid and glucose metabolism in human skeletal muscle. J Biol Chem. 2007 Jul 6;282(27):19313-20. Epub 2007 May 11. [PubMed:17500064]
  3. Fredenrich A, Grimaldi PA: PPAR delta: an uncompletely known nuclear receptor. Diabetes Metab. 2005 Feb;31(1):23-7. [PubMed:15803109]
External Links
PubChem Compound
9803963
PubChem Substance
175426999
ChemSpider
7979723
BindingDB
28661
ChEBI
73726
ChEMBL
CHEMBL38943
HET
7T1
Wikipedia
GW501516
PDB Entries
5u46

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
2CompletedTreatmentDyslipidemias1
4CompletedTreatmentBMI >30 kg/m2 / Cardiovascular Disease (CVD) / Lipid Disorders1
Not AvailableCompletedNot AvailableBMI >30 kg/m2 / Dyslipidemias / High Cholesterol1

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 Solubility0.000325 mg/mLALOGPS
logP5.43ALOGPS
logP5.7ChemAxon
logS-6.2ALOGPS
pKa (Strongest Acidic)3.51ChemAxon
pKa (Strongest Basic)2.14ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count4ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area59.42 Å2ChemAxon
Rotatable Bond Count8ChemAxon
Refractivity121.88 m3·mol-1ChemAxon
Polarizability43.39 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9873
Blood Brain Barrier+0.8877
Caco-2 permeable+0.5
P-glycoprotein substrateNon-substrate0.5964
P-glycoprotein inhibitor INon-inhibitor0.785
P-glycoprotein inhibitor IINon-inhibitor0.5719
Renal organic cation transporterNon-inhibitor0.7909
CYP450 2C9 substrateNon-substrate0.765
CYP450 2D6 substrateNon-substrate0.7962
CYP450 3A4 substrateNon-substrate0.5
CYP450 1A2 substrateInhibitor0.6861
CYP450 2C9 inhibitorInhibitor0.6573
CYP450 2D6 inhibitorNon-inhibitor0.8321
CYP450 2C19 inhibitorInhibitor0.7816
CYP450 3A4 inhibitorInhibitor0.7843
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.9405
Ames testNon AMES toxic0.696
CarcinogenicityNon-carcinogens0.8219
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.6222 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9993
hERG inhibition (predictor II)Non-inhibitor0.6917
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 phenoxyacetic acid derivatives. These are compounds containing an anisole where the methane group is linked to an acetic acid or a derivative.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Phenoxyacetic acid derivatives
Direct Parent
Phenoxyacetic acid derivatives
Alternative Parents
Trifluoromethylbenzenes / Thiophenol ethers / Phenoxy compounds / Phenol ethers / 2,4,5-trisubstituted thiazoles / Toluenes / Alkyl aryl ethers / Alkylarylthioethers / Heteroaromatic compounds / Sulfenyl compounds
show 10 more
Substituents
Phenoxyacetate / Trifluoromethylbenzene / 2,4,5-trisubstituted 1,3-thiazole / Phenoxy compound / Aryl thioether / Phenol ether / Thiophenol ether / Alkyl aryl ether / Toluene / Alkylarylthioether
show 25 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
organofluorine compound, aromatic ether, monocarboxylic acid, aryl sulfide, 1,3-thiazole (CHEBI:73726)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
General Function
Zinc ion binding
Specific Function
Ligand-activated transcription factor. Receptor that binds peroxisome proliferators such as hypolipidemic drugs and fatty acids. Has a preference for poly-unsaturated fatty acids, such as gamma-lin...
Gene Name
PPARD
Uniprot ID
Q03181
Uniprot Name
Peroxisome proliferator-activated receptor delta
Molecular Weight
49902.99 Da
References
  1. Buhrke T, Kibellus A, Lampen A: In vitro toxicological characterization of perfluorinated carboxylic acids with different carbon chain lengths. Toxicol Lett. 2013 Apr 12;218(2):97-104. doi: 10.1016/j.toxlet.2013.01.025. Epub 2013 Feb 4. [PubMed:23391484]
  2. Sarath Josh MK, Pradeep S, Vijayalekshmi Amma KS, Balachandran S, Abdul Jaleel UC, Doble M, Spener F, Benjamin S: Phthalates efficiently bind to human peroxisome proliferator activated receptor and retinoid X receptor alpha, beta, gamma subtypes: an in silico approach. J Appl Toxicol. 2014 Jul;34(7):754-65. doi: 10.1002/jat.2902. Epub 2013 Jul 11. [PubMed:23843199]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Agonist
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. Sarath Josh MK, Pradeep S, Vijayalekshmi Amma KS, Balachandran S, Abdul Jaleel UC, Doble M, Spener F, Benjamin S: Phthalates efficiently bind to human peroxisome proliferator activated receptor and retinoid X receptor alpha, beta, gamma subtypes: an in silico approach. J Appl Toxicol. 2014 Jul;34(7):754-65. doi: 10.1002/jat.2902. Epub 2013 Jul 11. [PubMed:23843199]

Drug created on November 18, 2007 11:24 / Updated on November 16, 2018 11:22