pIC50: 6.9 (GPR40)

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).

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.