At present, inhibitors of tyrosine kinase Abl are used for the therapy of CML, with already 3 such inhibitors (imatinib, dasatinib and nilotinib) approved for the therapy of primary patients and one more — bosutinib — has a high chance of being approved. Nevertheless, despite the high effectiveness of drugs in the first line of therapy, a small proportion of patients may acquire resistance or intolerance, which requires switching to another drug. Due to the high survival rate of patients with CML (median more than 10 years), the number of such events increases with time, and patients can switch to the 3rd and later lines of therapy. The effectiveness of drugs in this line of therapy is already significantly lower, which is an important medical problem. Also, patients can acquire a T315I mutation in the therapy of which currently only the preparation of the third generation of ponatinib is effective, which, however, has serious side effects (thrombotic and cardiovascular events, etc.).
Thus, CML therapy in the 3rd line and in patients with T315I mutation requires a more effective and safer drug in addition to those already available. To meet this need, a new selective inhibitor of the 3rd generation Abl—PF-114 is targeted.