GW-501516

Possibly Marketed Outside US

Details

Stereochemistry	ACHIRAL
Molecular Formula	C21H18F3NO3S2
Molecular Weight	453.498
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CC1=C(CSC2=CC=C(OCC(O)=O)C(C)=C2)SC(=N1)C3=CC=C(C=C3)C(F)(F)F

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	453.498
Charge	0
Count

Stereochemistry	ACHIRAL
Additional Stereochemistry	No
Defined Stereocenters	0 / 0
E/Z Centers	0
Optical Activity	NONE

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/16625823
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Peroxisome proliferator-activated receptor delta 29 Target ID: CHEMBL3979 Sources: https://www.ncbi.nlm.nih.gov/pubmed/16625823	Agonist 2678		1.1 nM [Ki]

Conditions

Condition	Modality	Highest Phase	Product
Dyslipidemia 30 Sources: https://www.ncbi.nlm.nih.gov/pubmed/18808307 https://clinicaltrials.gov/ct2/show/NCT00158899	Primary	Phase II 1132	Unknown Approved Use Unknown
Obesity 203 Sources: https://www.ncbi.nlm.nih.gov/pubmed/21816786	Primary	Phase IV 63	Unknown Approved Use Unknown
Metabolic syndrome 32 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22814748	Primary	Phase II 1132	Unknown Approved Use Unknown

PubMed

Title	Date	PubMed
A selective peroxisome proliferator-activated receptor delta agonist promotes reverse cholesterol transport.	2001 Apr 24	11309497
PPAR delta: an uncompletely known nuclear receptor.	2005 Feb	15803109
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	15821150
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	16197558
Role of AMP kinase and PPARdelta in the regulation of lipid and glucose metabolism in human skeletal muscle.	2007 Jul 6	17500064
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	17869249
Inflammatory pathways are activated during cardiomyocyte hypertrophy and attenuated by peroxisome proliferator-activated receptors PPARalpha and PPARdelta.	2008 Oct 24	18701451
Regulation of peroxisome proliferator-activated receptor-alpha by MDM2.	2009 Mar	19103650
Synthesis of isosteric selenium analog of the PPARbeta/delta agonist GW501516 and comparison of biological activity.	2010 Jul 15	20542425
Functional characterization of peroxisome proliferator-activated receptor-β/δ expression in colon cancer.	2011 Nov	21400612
Activation of PPARδ prevents endothelial dysfunction induced by overexpression of amyloid-β precursor protein.	2012 Dec 1	22886847
Phthalates efficiently bind to human peroxisome proliferator activated receptor and retinoid X receptor α, β, γ subtypes: an in silico approach.	2014 Jul	23843199

Patents

Sample Use Guides

In Vivo Use Guide

12 weeks of treatment with 2.5 mg, 5.0 mg or 5,0 mg, 10 mg

Route of Administration: Oral

In Vitro Use Guide

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 Dec 15 15:34:31 UTC 2023` Edited by `admin` on `Fri Dec 15 15:34:31 UTC 2023`
Record UNII	7I2HA1NU22
Record Status	`Validated (UNII)`
Record Version

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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)