AProtein kinase targeted. A number of these molecules are broad-spectrum kinase inhibitors. BStaurosporine class represents examples of broad-spectrum kinase inhibitors. PCD, preclinical development. These compounds may have progressed to phase I clinical trials.(426 amino acids) fused to exons 2–11 of c-Abl, occurs in 10% of adult cases and 5–10% of pediatric cases of acute lymphoblastic leukemia, but not in CML (9, 10). The Abl oncogene was isolated originally from the genome of the Abelson murine leukemia virus (A-MuLV)(11). This acutely transforming replication-defective virus encodes a transforming protein (p160v-Abl) with tyrosine-specific protein kinase activity. A-MuLV transforms fibroblasts in vitro and lymphoid cells in vitro and in vivo and was formed by recombination between Moloney murine leukemia virus (M-MuLV) and the murine c-Abl gene (11).

Expression of p210Bcr-Abl induces a disease resembling CML in mice (12, 13), confirming that the Bcr-Abl oncoprotein is a major factor in the pathophysiology of CML. Additional studies have shown that PTK activity is essential to the transforming function of Bcr-Abl (14). Thus, the presence of Bcr-Abl in the majority of CML patients, and the requirement of kinase activity for Bcr-Abl function, make this a particularly attractive target for design of a selective kinase inhibitor.