Figure 7. Mechanism studies for the inhibition effect of nobiletin on ABCB1 transporter.

(A) EC₅₀ measurements for stimulating P-gp ATPase activity by nobiletin; (B) IC₅₀ measurements for inhibiting 200 μM verapamil-stimulated P-gp ATPase activity. Luminescence was read on a luminometer and data was analyzed as described in Material and Method. (C) Docking analysis of nobiletin with human ABCB1 homology model. The binding poses of QZ59-RRR (PDB: 4M2S) (green) and nobiletin (orange) are shown in site 1. (D) The interactions between nobiletin and the surrounding residues. The red dotted line represents hydrogen bond between atoms. (E) A two dimensional interaction sketch between nobiletin and its binding site residues of human ABCB1 is shown. Residues are shown as colored bubbles, cyan indicates polar and green indicates hydrophobic residues.