ABL kinases,

Kinases Abl kinase Mouse cDNA Cancer, acute lymphocytic leukemia, chronic myelocytic leukemia, chronic neutrophilic leukemia Regulation of cytoskeletal organization and movement... 

Kopt Ta M, Falinski R, Nowicki MO et al. BCR/ABL kinase induces self-mutagenesis via reactive oxygen species to encode imatinib resistance. Blood 2006 108 319-327. 

Crystallography studies showed that imatinib binds to an inactive form of Abl [36,37]. In this bound conformation the activation loop of the Abl kinase domain is distinct from that of both the inactive and active forms of the SFKs, explaining why imatinib does not inhibit these kinases. The crystal structure also revealed that the Thr 315 residue was involved in a key hydrogen bonding interaction with the C-2 amino group of imatinib. 

The search for additional new Abl inhibitors continued and at the 2004 meeting of the American Society of Hematology (ASH), Novartis disclosed an Abl kinase inhibitor with improved activity over imatinib [39]. The first literature report on AMN107 (3) appeared in early 2005 [40] (Scheme 2). The structure of AMN107 diverges from that of imatinib in two areas. First, the... 

Several of the new Bcr-Abl kinase inhibitors reported subsequent to imatinib also inhibit Src, a non-receptor tyrosine kinase. In 2000, il was re-porled lhat the known Src inhibitor PD180970 (12) also inhibited Abl kinase [73] (Scheme 5). This property was soon found to be shared by several other pyrido[2,3-d]pyrimidine Src inhibitors including PD173955 (13) [74] (Scheme 5). A crystal structure of PD 173955 demonstrated that this compound could bind to both the active and inactive form of Abl [37]. While the conformation of active Src kinase is similar to that of active Abl, the conformations of the inactive kinases are quite different. Unlike PD 173955, imatinib only binds the inactive form of Abl. The inability of imatinib to inhibit Src is... 

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