GW-1100

GW-1100 is a selective GPR40 antagonist with a pIC₅₀ of 6.9. GW1100 acts as a GPR40 inverse agonist. IC50 & Target: pIC50: 6.9 (GPR40)^[1] In Vitro: GW-1100 (GW1100) dose dependently inhibits GPR40-mediated Ca²⁺ elevations stimulated by GW9508 and linoleic acid (pIC₅₀ 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 (pEC₅₀=7.17±0.08 in the absence and pEC₅₀=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 pEC₅₀ response^[2]. 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)^[3]. 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^[4].