Figure 3. BCR-ABL1 Tyrosine Kinase Inhibitors and Resistance Mechanisms.

Chemical structures and published X-ray crystallographic structures of ABL1 complexed with kinase inhibitors are shown. Residues at which mutations are associated with strong resistance to a given TKI are indicated in red, while those associated with lesser degrees of resistance are listed in orange. Both T315 and E255 mutations do lead to an increase in the IC₅₀ for ponatinib; however, they do not typically lead to clinical resistance in isolation, but do as a compound mutation. The structure of ABL1 complexed with asciminib shows nilotinib in the ATP-binding site for reference. T315I is indicated in purple for visual reference (Cowan-Jacob et al., 2007; Levinson and Boxer, 2012; O’Hare et al., 2009; Tokarski et al., 2006; Weisberg et al., 2005; Wylie et al., 2017).