Structure-Activity Relationship of Indole-Tethered Pyrimidine Derivatives that Concurrently Inhibit Epidermal Growth Factor Receptor and Other Angiokinases
Fig 9
Comparison of the binding poses of MKP123 and MKP122 with MKP101.
Binding poses of (A) MKP123 (carbon atoms in green) and (B) MKP122 (carbon atoms in green) with MKP101 (carbon atoms in ivory). The lipophilic potential surface of the ATP-binding site of EGFR was created using the MOLCAD implemented in Sybyl-X 2.0. 2D-interaction diagram of the binding model of (C) MKP123 and (D) MKP122 displaying the amino acid residues within 4.0Å of the ligand. Acidic, hydrophobic, basic, polar, and other residues at the active site are represented by red, green, purple, blue, and gray spheres, respectively. The hydrogen bond between the ligand and backbone is shown in dashed pink lines. The π-π stacking interaction is shown with a green line. Unlike MKP101, the indole rings of MKP123 and MKP122 occupy a lipophilic pocket without a hydrogen bond with the backbone of Phe856, and their aniline moiety was docked in the hinge region. ATP, adenosine triphosphate; EGFR, epidermal growth factor receptor.