GW9508

Names

[ Name ]:
GW9508

[Synonym ]:
Benzenepropanoic acid, 4-[[(3-phenoxyphenyl)methyl]amino]-
3-{4-[(3-Phenoxybenzyl)amino]phenyl}propanoic acid
gw9508
GW-9508

Biological Activity

[Description]:

GW9508 is a potent and selective agonist for FFA1 (GPR40) with pEC50 of 7.32, 100-fold selective against GPR120, stimulates insulin secretion in a glucose-sensitive manner.IC50 value: 7.32 (pEC50) [1]Target: GPR40GW9508 is shown to be at least 100-fold selective against 220 other GPCRs, 60 kinases, 63 proteases, seven integrins and 20 nuclear receptors including PPARα, δ and γ (pEC50 4.0, 4 and 4.9, respectively). GW9508 produces a concentration-dependent increase in intracellular Ca2+ concentrations via GPR40 receptor activation and the GPR120 receptor. GW9508 is active as an agonist at both GPR40 and GPR120, it is approximately 100-fold selective for GPR40 with respect to GPR120. GW9508 produces a concentration-dependent increase (pEC50=6.14) in glucose-stimulated insulin secretion at high glucose levels (25 mM). GW9508 dose dependently stimulated insulin secretion in a glucose-sensitive manner in MIN6 cells. Furthermore, GW9508 is able to potentiate the KCl-mediated increase in insulin secretion in MIN6 cells. [1] GW9508 induced hyperpolarization and opening of KATP channels in rat β-cells. [2] GW9508 inhibits CCL17 and CCL5 expression in a pertussis toxin-sensitive manner. GW9508 further suppresses expression of IL-11, IL-24, and IL-33 induced in HaCaT cells by TNF-α and IFN-γ. GW9508 also inhibits CCL5 and CXCL10 production by normal human epidermal keratinocytes. [3]

[Related Catalog]:

Signaling Pathways >> GPCR/G Protein >> GPR40

Research Areas >> Metabolic Disease

[References]

[1]. Briscoe CP, et al. Pharmacological regulation of insulin secretion in MIN6 cells through the fatty acid receptor GPR40: identification of agonist and antagonist small molecules. Br J Pharmacol. 2006 Jul;148(5):619-28.

[2]. Zhao YF, et al. Activation of ATP-sensitive potassium channels in rat pancreatic beta-cells by linoleic acid through both intracellular metabolites and membrane receptor signalling pathway. J Endocrinol, 2008, 198(3), 533-540.

[3]. Fujita T, et al. A GPR40 agonist GW9508 suppresses CCL5, CCL17, and CXCL10 induction in keratinocytes and attenuates cutaneous immune inflammation. J Invest Dermatol, 2011, 131(8), 1660-1667.

[Related Small Molecules]

TAK-875 | GW-1100 | DC 260126 | PBI-4050 sodium salt | GPR40 Activator 2 | TUG-770 | AMG 837 | FAA1 agonist-1 | GPR40 Activator 1 | AM-1638 | GPR40 Agonist 2

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Boiling Point ]:
538.4±45.0 °C at 760 mmHg

[ Molecular Formula ]:
C₂₂H₂₁NO₃

[ Molecular Weight ]:
347.407

[ Flash Point ]:
279.4±28.7 °C

[ Exact Mass ]:
347.152130

[ PSA ]:
58.56000

[ LogP ]:
4.74

[ Vapour Pressure ]:
0.0±1.5 mmHg at 25°C

[ Index of Refraction ]:
1.641

[ Storage condition ]:
Store at RT

[ Water Solubility ]:
DMSO: >20mg/mL

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS05, GHS07, GHS09

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H302-H315-H318-H335-H410

[ Precautionary Statements ]:
P261-P273-P280-P305 + P351 + P338-P501

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Faceshields;Gloves

[ Hazard Codes ]:
Xn,N

[ Risk Phrases ]:
22-37/38-41-50/53

[ Safety Phrases ]:
26-39-60-61

[ RIDADR ]:
UN 3077 9 / PGIII

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Articles

Omega-3 fatty acids and other FFA4 agonists inhibit growth factor signaling in human prostate cancer cells.

J. Pharmacol. Exp. Ther. 352(2) , 380-94, (2015)

Omega-3 fatty acids (n-3 FAs) are proposed to have many beneficial effects on human health. However, the mechanisms underlying their potential cancer preventative effects are unclear. G protein-couple...

Short-chain fatty acid sensing in rat duodenum.

J. Physiol. 593(3) , 585-99, (2015)

Luminal lipid in the duodenum modulates gastroduodenal functions via the release of gut hormones and mediators such as cholecystokinin and 5-HT. The effects of luminal short-chain fatty acids (SCFAs) ...

Novel identification of the free fatty acid receptor FFAR1 that promotes contraction in airway smooth muscle.

Am. J. Physiol. Lung Cell. Mol. Physiol. 309 , L970-82, (2015)

Obesity is one of the major risk factors for asthma. Previous studies have demonstrated that free fatty acid levels are elevated in the plasma of obese individuals. Medium- and long-chain free fatty a...