Role of tyrosine-kinase inhibitor selectivity in development of adverse effects during treatment of chronic myeloid leukemia

A.A. Zeifman1,2, E.Yu. Chelysheva3, A.G. Tukrina3, and G.G. Chilov1,2

1 N.D. Zelinsky Institute of Organic Chemistry, RAS, Moscow, Russian Federation

2 Fusion Pharma LLC, Moscow, Russian Federation

3 Hematology Research Center, RF MH, Moscow, Russian Federation


ABSTRACT

This review focuses on association between the selectivity of Bcr-Abl kinase inhibitors and the spectrum of their adverse effects during treatment of patients with chronic myeloid leukemia. The data on the structure and natural biochemical functions of the well-known adverse targets for inhibitors of Bcr-Abl kinases, including BRAF, FMS, EGFR, PDGFR, PYK2, TIE2, and VEGFR1/2/3 are summarized, and the potential association between their off-target inhibition and adverse effects of tyrosine-kinase inhibitors is suggested.


Keywords: chronic myeloid leukemia, tyrosine-kinase inhibitors, selectivity, imatinib, nilotinib, dasatinib, ponatinib, PF-114, BRAF, FMS, EGFR, PDGFR, PYK2, TIE2, VEGFR1/2/3.

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