Alkynylnicotinaamide-Based Compounds as ABL1 Inhibitors with Potent Activities against Drug-Resistant CML Harboring ABL1(T315I) Mutant Kinase

Chronic Myeloid Leukemia makes up about 10% of all leukemia diagnoses. Although the 5-year survival rate has increased from 6% to 90% in the last 30 years from the introduction of imatinib, there are several mutated forms of the cancer that are resistant treatment. Treatments such as Ponatinib can be used to treat CML patients that harbor the T315I mutation, but they have toxic effects on the body. Safer treatments need to be discovered to inhibit the proliferation of these resistant lines by inhibiting the activity of proteins and mutated proteins. Through research done utilizing cell cultures of CML lines K562 and KCL22 and the resistant line KCL22-IR, several compounds have been found to be effective in inhibiting the proliferation of these cancer cell lines. This research suggests that isoquinoline- or napthyridine- based compounds could be safer alternatives for treating drug resistant CML.