885101-89-3 Usage
Description
GW9508 is a selective agonist at the free fatty acid receptor, FFA1/4 (GPR40 and GPR120), which displays anti-allodynic and anti-hyperalgesic effects in mouse inflammatory and neuropathic pain models. It also inhibits LPA-induced proliferation of DU145 and PC-3 cells, decreases hepatic lipid accumulation in a high-fat diet steatosis mouse model, and promotes brown adipose tissue thermogenesis.
Uses
Used in Diabetes Treatment:
GW9508 is used as a GPR40 full agonist to regulate glucose in rats and can be applied to the treatment of type 2 diabetes. It is also a GPR120 selective and potent agonist, which is used in the treatment of type 2 diabetes due to GPR120's ability to mediate GLP-1 secretion, insulin sensitization, and anti-obesity effects.
Used in Pharmaceutical Research:
GW9508, a selective FFA1/GPR40 agonist, is used to differentiate and characterize the free fatty acid receptor FFA1/GPR40. It is used to study the role of FFA1/GPR40 receptors in processes such as the free fatty acid enhancement of glucose-stimulated insulin release and type 2 diabetes.
Used in Bone Loss Prevention:
GW9508 is used to study the process by which FFA1/GPR40 receptors protect from ovariectomy-induced bone loss in vivo through inhibition of osteoclast differentiation.
Used in Pain Management Research:
GW9508 is used to study the process by which FFA1/GPR40 receptors suppress complete Freund's adjuvant (CFA)-induced inflammatory chronic pain.
Used in Cancer Research:
GW9508 is used to inhibit LPA-induced proliferation of DU145 and PC-3 cells, which are related to cancer research.
Used in Metabolic Research:
GW9508 is used to decrease hepatic lipid accumulation in a high-fat diet steatosis mouse model and promote brown adipose tissue thermogenesis, contributing to the study of metabolic processes.
Biological Activity
Potent and selective agonist for the free fatty acid receptor FFA 1 (GPR40) (pEC 50 values are 7.32, < 4.3 and < 4.3 for FFA 1 , FFA 2 and FFA 3 receptors respectively). Inactive against a range of other GPCRs, kinases, proteases, integrins and PPARs. Potentiates glucose-stimulated insulin secretion in MIN6 cells (pEC 50 = 6.14).
Biochem/physiol Actions
GW9508 is a selective FFA1/GPR40 agonist. GPR40 was formerly an orphan G protein-coupled receptor whose endogenous ligands have now been identified as free fatty acids (FFAs). The receptor, named FFA receptor 1, has been implicated in the pathophysiology of type 2 diabetes and is a drug target because of its role in FFA-mediated enhancement of glucose-stimulated insulin release. GW9508 showed greater than 500-fold selectivity for GPR40 over GPR41 and GPR43 and possessed a good in vitro and in vivo profile with excellent bioavailability. GW9508 stimulated intracellular Ca2+ mobilization in human embryonic kidney HEK-293 cells expressing GPR40 or GPR120, but not in the parent HEK-293 cell line. GW9508 dose dependently potentiated glucose-stimulated insulin secretion in MIN6 cells, but not in primary rat or mouse islets. GW9508 potentiates the KCl-mediated increase in insulin secretion in MIN6 cells.
References
1) Briscoe et al. (2006) Pharmacological regulation of insulin secretion in MIN6 cells through the fatty acid receptor GPR40: identification of agonist and antagonist molecules, Br. J. Pharmacol. 148 619
2) Karki et al. (2015), Attenuation of inflammatory and neuropathic pain behaviors in mice through activation of free fatty acid receptor GPR40; Mol. Pain, 11 6
3) Liu et al. (2015), Omega-3 fatty acids and other FFA4 agonists inhibit growth factor signaling in human prostate cancer cells; J. Pharmacol. Exp. Ther., 352 380
4) Ou et al. (2014), Activation of free fatty acid receptor 1 improves hepatic steatosis through a p38-dependent pathway; J. Mol. Endocrinol., 53 165
5) Kim et al. (2016), Eicosapentaenoic Acid Potentiates Brown Thermogenesis through FFAR4-dependent Up-regulation of miR-30b and miR-378; J. Biol. Chem., 291 2055
Check Digit Verification of cas no
The CAS Registry Mumber 885101-89-3 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 8,8,5,1,0 and 1 respectively; the second part has 2 digits, 8 and 9 respectively.
Calculate Digit Verification of CAS Registry Number 885101-89:
(8*8)+(7*8)+(6*5)+(5*1)+(4*0)+(3*1)+(2*8)+(1*9)=183
183 % 10 = 3
So 885101-89-3 is a valid CAS Registry Number.
InChI:InChI=1/C22H21NO3/c24-22(25)14-11-17-9-12-19(13-10-17)23-16-18-5-4-8-21(15-18)26-20-6-2-1-3-7-20/h1-10,12-13,15,23H,11,14,16H2,(H,24,25)
885101-89-3Relevant articles and documents
Solid phase synthesis and SAR of small molecule agonists for the GPR40 receptor
McKeown, Stephen C.,Corbett, David F.,Goetz, Aaron S.,Littleton, Thomas R.,Bigham, Eric,Briscoe, Celia P.,Peat, Andrew J.,Watson, Steve P,Hickey, Deirdre M.B.
, p. 1584 - 1589 (2007)
The discovery, synthesis and structure-activity relationship (SAR) of novel carboxylic acid agonists for GPR40 are described. Aryl propionic acid 1, identified from a high throughput screen, was selected for chemical exploration. Compound 2 was identified as our lead molecule through efficient solid phase combinatorial array chemistry and had an attractive in vitro and in vivo pharmacokinetic profile in rat. These ligands may prove useful in establishing a role for GPR40 in insulin regulation.
COMPOUNDS AND COMPOSITIONS FOR THE TREATMENT OF CANCER
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Page/Page column 41-42, (2012/08/07)
New uses for phenylketone carboxylate compounds and substituted aromatic compounds of Formula I, Formula I.1, Formula I.2, Formula IA, Formula IB, Formula IC and Formula II and their pharmaceutical acceptable salts for the treatment of cancer. The use of
