306974-70-9 Usage
Description
GW-1100, also known as GW1100 (306974-70-9), is a selective antagonist of the G protein-coupled receptor GPR40. It is characterized by its ability to inhibit GPR40-mediated Ca2+ increases stimulated by GW9508 or linoleic acid, with a pIC50 of 5.99 for either agonist. GW-1100 effectively blocks the effects of GPR40 activation on insulin secretion in cells and does not influence calcium mobilization mediated by GPR120.
Uses
Used in Pharmaceutical Industry:
GW-1100 is used as a GPR40 antagonist for the purpose of reversing the effects of GPR40 agonists, which induce glucose-stimulated insulin secretion. This makes it a potential candidate for the development of treatments targeting conditions related to insulin secretion and glucose metabolism.
Used in Research Applications:
In the field of research, GW-1100 is used as a tool to study the role of GPR40 in various biological processes, including insulin secretion and glucose homeostasis. By blocking the receptor, researchers can gain insights into the underlying mechanisms and potential therapeutic targets for related diseases.
Biological Activity
GW-1100 is a selective GPR40 antagonist with pIC50 of 6.9.
in vitro
GW-1100 (GW1100) dose dependently inhibits GPR40-mediated Ca 2+ elevations stimulated by GW9508 and linoleic acid (pIC 50 values of 5.99±0.03 and 5.99±0.06, respectively). GW-1100 at a concentration of 1 μM produces a significant rightward shift in the concentration-response curve to GW9508 (pEC 50 =7.17±0.08 in the absence and pEC 50 =6.79±0.09 in the presence of 1 μM GW-1100; P<0.05; n=3). At concentrations of GW-1100 of 3 μM and higher a significant decrease in the maximal response is observed with a continuing rightward shift in the pEC 50 response. GW-1100 (GW1100) reduces FFAR1 ligand-induced intracellular calcium in CHO-K1/bFFAR1 cells and neutrophils. CHO-K1/bFFAR1 cells are incubated for 15 min with 10 μM GW1100 or vehicle (0.1% DMSO) and then stimulated with vehicle, oleic acid, linoleic acid or GW9508. GW-1100 significantly reduces the increase in intracellular calcium induced by 300 μM oleic acid (AUC (60-150 s) , p<0.05), 100 μM linoleic acid (AUC (60-150 s) , p<0.05) and 10 μM GW9508 (AUC (60-150 s) , p<0.05).
in vivo
The intracerebroventricular injection of DHA (50 μg) and GW9508 (1.0 μg), a GPR40-selective agonist, significantly reduces mechanical allodynia and thermal hyperalgesia at day 7, but not at day 1, after CFA injection. These effects are inhibited by intracerebroventricular pretreatment with GW-1100 (10 μg), a GPR40 antagonist.
References
1) Brisco?et al. (2006),?Pharmacological regulation of insulin secretion in MIN6 cells through fatty acid receptor GPR40: identification of agonist and antagonist molecules; Br. J. Pharmacol.,?148?619
2) Nagatake?et al. (2018),?The 17,18-Epoxytetraenoic acid-G protein-coupled receptor 40 axis ameliorates contact hypersensitivity by inhibiting neutrophil mobility in mice and cynomolgus macaques; J. Allergy Clin. Immunol.,?142?470 [Focus Biomolecules Citation]
Check Digit Verification of cas no
The CAS Registry Mumber 306974-70-9 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 3,0,6,9,7 and 4 respectively; the second part has 2 digits, 7 and 0 respectively.
Calculate Digit Verification of CAS Registry Number 306974-70:
(8*3)+(7*0)+(6*6)+(5*9)+(4*7)+(3*4)+(2*7)+(1*0)=159
159 % 10 = 9
So 306974-70-9 is a valid CAS Registry Number.
306974-70-9Relevant articles and documents
Feasible synthesis of the GPR40 antagonist by contructing 2-thiouracil ring VIA acid mediated cyclization
Zhao, Yongfeng,Liao, Jiayu
, p. 1145 - 1151 (2011/06/10)
GW1100 is an antagonist of GPR40 identified by high throughput screening recently. The feasible synthesis of GW1100 has been developed in mild conditions. The key step involves the cyclization of the 2-thiouracil heterocycle under acidic conditions at room temperature. The Japan Institute of Heterocyclic Chemistry.
