Interaction of the N-(3-Methylpyridin-2-yl)amide Derivatives of Flurbiprofen and Ibuprofen with FAAH: Enantiomeric Selectivity and Binding Mode
Fig 5
Inhibition of rat wild-type and FAAHT488A by A.
(R)-Flu-AM1 and B. carprofen. Samples were incubated for 18 h with inhibitor and substrate (0.5 μM [3H]AEA). The concentrations of lysates used were FAAHwt, 0.04 μg/assay, FAAHT488A, 0.4 μg/assay, empty vector 0.36 μg/assay. Shown are means ± SEM, N = 3–6. The pI50 values, with corresponding IC50 and nH values in brackets were: (R)-Flu-AM1: FAAHwt, 5.08±0.03 (8.3 μM; nH = 1.02±0.07); FAAHT488A, 4.55±0.07 (28 μM; nH = 1.47±0.37), FAAHwt + empty vector, 5.10±0.02 (8.0 μM; nH = 0.99±0.06). Carprofen: FAAHwt, 4.43±0.02 (37 μM, nH = 3.00±0.31); FAAHT488A, 4.32±0.04 (48 μM, nH = 2.43±0.37), FAAHwt + empty vector, 4.50±0.01 (32 μM; nH = 4.28±0.41. Note that for carprofen and wild-type FAAH, the analyses suggested that a curve with a maximum inhibition of 82–91% fitted the data better than a curve with 100% maximum inhibition, and these values have been used here.
