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Details

Stereochemistry ACHIRAL
Molecular Formula C21H18F3NO3S2
Molecular Weight 453.5007
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of GW-501516

SMILES

Cc1cc(ccc1OCC(=O)O)SCc2c(C)nc(-c3ccc(cc3)C(F)(F)F)s2

InChI

InChIKey=YDBLKRPLXZNVNB-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Molecular Formula C21H18F3NO3S2
Molecular Weight 453.5007
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: description was created based on several sources, including: http://adisinsight.springer.com/drugs/800015062 | https://en.wikipedia.org/wiki/GW501516

GW-501516 is a peroxisome proliferator-activator receptor-delta agonist for the potential treatment of dyslipidemia, hyperlipidemia, metabolic diseases and cardiovascular diseases. GW501516 treatment is associated with significant improvements in multiple lipid profile components (TG, LDL-C, HDL-C, free fatty acids and apoB, apoA-I and apoA-II) and a shift in LDL particle size from small dense to larger, less dense particles. Despite these promising early results, the further investigation and development of GW501516 was discontinued after observations in animal studies of its association with the rapid induction of cancers in several organs (liver, stomach, tongue, skin, bladder, ovaries, womb and testes).

CNS Activity

Curator's Comment:: GW501516 have very poor ability in terms of brain penetration. Known to be CNS penetrant in rodents. Human data not available.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
1.1 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
Primary
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
A selective peroxisome proliferator-activated receptor delta agonist promotes reverse cholesterol transport.
2001 Apr 24
PPAR delta: an uncompletely known nuclear receptor.
2005 Feb
Nanomolar and micromolar effects of 15-deoxy-delta 12,14-prostaglandin J2 on amnion-derived WISH epithelial cells: differential roles of peroxisome proliferator-activated receptors gamma and delta and nuclear factor kappa B.
2005 Jul
Rosiglitazone induces interleukin-1 receptor antagonist in interleukin-1beta-stimulated rat synovial fibroblasts via a peroxisome proliferator-activated receptor beta/delta-dependent mechanism.
2005 Mar
Statins and PPARalpha agonists induce myotoxicity in differentiated rat skeletal muscle cultures but do not exhibit synergy with co-treatment.
2005 Nov 1
Gene expression profiling of potential peroxisome proliferator-activated receptor (PPAR) target genes in human hepatoblastoma cell lines inducibly expressing different PPAR isoforms.
2005 Oct 3
Effects of bezafibrate, PPAR pan-agonist, and GW501516, PPARdelta agonist, on development of steatohepatitis in mice fed a methionine- and choline-deficient diet.
2006 Apr 24
Niacin induces PPARgamma expression and transcriptional activation in macrophages via HM74 and HM74a-mediated induction of prostaglandin synthesis pathways.
2006 Feb 28
Role of AMP kinase and PPARdelta in the regulation of lipid and glucose metabolism in human skeletal muscle.
2007 Jul 6
Indomethacin induces apoptosis in 786-O renal cell carcinoma cells by activating mitogen-activated protein kinases and AKT.
2007 Jun 1
PPARdelta, but not PPARalpha, activates PGC-1alpha gene transcription in muscle.
2007 Mar 23
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.
2007 Oct 2
In vivo imaging reveals selective peroxisome proliferator activated receptor modulator activity of the synthetic ligand 3-(1-(4-chlorobenzyl)-3-t-butylthio-5-isopropylindol-2-yl)-2,2-dimethylpropanoic acid (MK-886).
2008 May
Ligand activation of peroxisome proliferator-activated receptor-beta/delta inhibits cell proliferation in human HaCaT keratinocytes.
2008 Nov
Inflammatory pathways are activated during cardiomyocyte hypertrophy and attenuated by peroxisome proliferator-activated receptors PPARalpha and PPARdelta.
2008 Oct 24
On the mechanism for PPAR agonists to enhance ABCA1 gene expression.
2009 Aug
Regulation of peroxisome proliferator-activated receptor-alpha by MDM2.
2009 Mar
Cross-talk between vitamin D receptor (VDR)- and peroxisome proliferator-activated receptor (PPAR)-signaling in melanoma cells.
2009 Sep
Rosiglitazone activation of PPARgamma suppresses fractalkine signaling.
2010 Feb
Synthesis of isosteric selenium analog of the PPARbeta/delta agonist GW501516 and comparison of biological activity.
2010 Jul 15
Peroxisome proliferator-activated receptor delta regulation of miR-15a in ischemia-induced cerebral vascular endothelial injury.
2010 May 5
Cellular and pharmacological selectivity of the peroxisome proliferator-activated receptor-beta/delta antagonist GSK3787.
2010 Sep
GW501516, a PPARδ agonist, ameliorates tubulointerstitial inflammation in proteinuric kidney disease via inhibition of TAK1-NFκB pathway in mice.
2011
Dual acting and pan-PPAR activators as potential anti-diabetic therapies.
2011
Functional characterization of peroxisome proliferator-activated receptor-β/δ expression in colon cancer.
2011 Nov
A cardiac-specific robotized cellular assay identified families of human ligands as inducers of PGC-1α expression and mitochondrial biogenesis.
2012
Activation of PPARδ prevents endothelial dysfunction induced by overexpression of amyloid-β precursor protein.
2012 Dec 1
Role of Peroxisome Proliferator-Activated Receptor β/δ and B-Cell Lymphoma-6 in Regulation of Genes Involved in Metastasis and Migration in Pancreatic Cancer Cells.
2013
In vitro toxicological characterization of perfluorinated carboxylic acids with different carbon chain lengths.
2013 Apr 12
Phthalates efficiently bind to human peroxisome proliferator activated receptor and retinoid X receptor α, β, γ subtypes: an in silico approach.
2014 Jul
Patents

Sample Use Guides

12 weeks of treatment with 2.5 mg, 5.0 mg or 5,0 mg, 10 mg
Route of Administration: Oral
In 1BR3N human skin fibroblasts, the 1 uM of GW501516 produced a 3.4-fold increase in ABCA1 expression and a 2-fold increase in apoA1-specific cholesterol efflux. In FHS74 human intestinal cells, the 1 uM of GW501516 produced a 2.1-fold increase in ABCA1 expression.
Substance Class Chemical
Created
by admin
on Fri Jun 25 23:39:46 UTC 2021
Edited
by admin
on Fri Jun 25 23:39:46 UTC 2021
Record UNII
7I2HA1NU22
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
GW-501516
Common Name English
CARDARINE
Common Name English
GSK-516
Code English
GW-1516
Code English
(2-METHYL-4-(((4-METHYL-2-(4-(TRIFLUOROMETHYL)PHENYL)-1,3-THIAZOL-5-YL)METHYL)THIO)PHENOXY)ACETIC ACID
Systematic Name English
GW501516
Code English
Classification Tree Code System Code
DSLD 3989 (Number of products:9)
Created by admin on Fri Jun 25 23:39:46 UTC 2021 , Edited by admin on Fri Jun 25 23:39:46 UTC 2021
DSLD 3986 (Number of products:12)
Created by admin on Fri Jun 25 23:39:46 UTC 2021 , Edited by admin on Fri Jun 25 23:39:46 UTC 2021
Code System Code Type Description
FDA UNII
7I2HA1NU22
Created by admin on Fri Jun 25 23:39:46 UTC 2021 , Edited by admin on Fri Jun 25 23:39:46 UTC 2021
PRIMARY
WIKIPEDIA
GW501516
Created by admin on Fri Jun 25 23:39:46 UTC 2021 , Edited by admin on Fri Jun 25 23:39:46 UTC 2021
PRIMARY
PUBCHEM
9803963
Created by admin on Fri Jun 25 23:39:46 UTC 2021 , Edited by admin on Fri Jun 25 23:39:46 UTC 2021
PRIMARY
DRUG BANK
DB05416
Created by admin on Fri Jun 25 23:39:46 UTC 2021 , Edited by admin on Fri Jun 25 23:39:46 UTC 2021
PRIMARY
CAS
317318-70-0
Created by admin on Fri Jun 25 23:39:46 UTC 2021 , Edited by admin on Fri Jun 25 23:39:46 UTC 2021
PRIMARY
Related Record Type Details
TARGET -> AGONIST
Related Record Type Details
ACTIVE MOIETY