AMG 837: A Novel GPR40/FFA1 Agonist that Enhances Insulin Secretion and Lowers Glucose Levels in Rodents
Figure 1
In vitro characterization of AMG 837.
(A) The chemical structure of AMG 837 is shown. (B–D) The activity of AMG 837 in various GPCR assays was assessed as described in Materials and Methods. Dose response relationships of AMG 837 in GTPγS binding (B), inositol phosphate accumulation (C) and aequorin Ca2+ flux assays (D) in cell lines overexpressing GPR40/FFA1 were determined. (D–G) In order to compare the activity of AMG 837 to fatty acids, plasmid titration experiments where either 5000 ng (D), 500 ng (E), 50 ng (F) or 5 ng (G) of GPR40 expression plasmid was co-transfected with aequorin expression plasmids into CHO cells. Activity of AMG 837 (blue diamond) was compared to the naturally occurring GPR40/FFA1 ligand docosahexaenoic acid (DHA, green square) in aequorin Ca2+ flux. (H) The activity of AMG 837 in the aequorin Ca2+ flux assays in the presence of 0.01% (v/v) purified human serum albumin (HSA, blue diamond), 0.625% (w/v) HSA (green square) or human serum (100% v/v, black circle) was determined.