Fig. 5.

Function of selected 4-CMTB SAR ligands at hFFA2-eYFP. A, 4-CMTB isopropyl replacement variants (replacement area on 4-CMTB indicated on the structure by a circle) in the [³⁵S]GTPγS incorporation assay demonstrate chain length and bulk dependence for maximal efficacy. Significant differences from 4-CMTB maximum are indicated. *, p < 0.05, **, p < 0.01; n.s., not significant, according to one-way ANOVA with Dunnett's post hoc analysis (n = 4). B, HWD004 is also a positive allosteric modulator at 10 μM in the presence of increasing propionate concentrations. Arrow indicates shift in potency. *, p < 0.05 according to Student's t test. C, not all 4-CMTB analogs displayed agonist activity at hFFA2-eYFP. D, inactive (HWD015 and HWD016) or weakly efficacious (HWD001, HWD008) ligands were tested for allosterism (10 μM fixed concentration of HWD ligands) but failed to alter the potency of propionate. n.s., no significant difference in potencies according to one-way ANOVA. E, neither HWD015 nor HWD016 could compete at 10 μM with 4-CMTB at hFFA2-eYFP. Data represent mean ± S.E.M. of three independent experiments.