TABLE 5

Alanine substitution of residues of drug-binding pocket interacting with compound 8 alters effect on ATPase activity of P-gp

Summary of the interaction of compound 8 with residues in the transmembrane region of P-gp. The effect of compound 8 on the basal ATPase activity of mutant P-gps was tested at 2.5 and 5 μM. As in Table 4, the percentage of stimulation or inhibition by compound 8 is shown and basal ATPase activity is considered 0%. ATPase activity was measured in total membranes prepared from High-Five insect cells expressing mutant P-gp. The values indicate stimulation (upward arrows) or inhibition (downward arrows) of basal ATPase activity (mean ± S.D. from three independent experiments, except for F343Y mutant, in which the average of two independent experiments is given).