Definition

An orally bioavailable, Bcr-Abl tyrosine kinase inhibitor (TKI), with potential antineoplastic activity. Upon administration, Bcr-Abl kinase inhibitor K0706 selectively targets and binds to the Bcr-Abl fusion oncoprotein, including various Bcr-Abl mutant forms, such as those with the ‘gatekeeper’ resistance mutation T315I. This inhibits proliferation of Bcr-Abl-expressing tumor cells. The Bcr-Abl fusion protein is an aberrantly activated tyrosine kinase produced by certain leukemia cells. T315I, a threonine (T) to isoleucine (I) amino acid substitution at position 315 in the tyrosine-protein kinase ABL1 portion of the Bcr-Abl fusion protein, plays a key role in resistance to certain chemotherapeutic agents, and its expression is associated with poor prognosis.