Comparative chemical structures and 3-dimensional (3-D) molecular models of ATP-based inhibitor AP23464 and the previously described inhibitors imatinib mesylate and PD173955 complexed with Abl kinase. (A) Chemical structures of AP23464, imatinib mesylate, and PD173955. (B) Three-dimensional molecular model of AP23464 complexed with Abl kinase in its ATP-binding active conformation. Residues that result in significantly decreased imatinib mesylate inhibitory potency if mutated are highlighted. (C) X-ray structure of imatinib mesylate complexed with Abl kinase in an induced fit conformation as previously described.²¹  (D) X-ray structure of PD173955 complexed with Abl kinase in an induced fit conformation as previously described.²¹  (E) Three-dimensional molecular model overlay of AP23464, imatinib mesylate, and PD173955 in their Abl kinase bound conformations, illustrating differences in their use of 3-D chemical space arising from varying structures and modes of binding. See “Discussion” for further description of the inhibitors, molecular modeling, and correlation with Abl kinase mutant structure-activity studies.