“…Consistency for ligand-directed binding towards Pro1158, Met1160, and/or Tyr1230 was reported with different c-Met inhibitors bearing quinolinylmethyl purine, dihydroquinoline, thiadiazolo [2,3-c]-triazin, and indazole scaffolds showing low-to-sub micromolar c-Met inhibition activities [ 104 , 105 , 106 , 107 , 108 ]. Studies employing quantitative structural activity relationship-aided molecular dynamics design of potent and exquisitely selective c-Met inhibitors bearing heterocyclic fused ring scaffolds [ 109 , 110 ]. These studies highlighted hydrophobic interactions with Val1092, Ala1108, Leu1157, Tyr1159, Met1211, and Tyr1230, as well as hydrogen bonding with Met1160 and Asp1222, particularly for ligands with hydrogen bond donors, for favor stabilization and free binding energy contributions.…”