BCR-ABL Inhibitors in Targeted Therapy of Chronic Myeloid Leukemia

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Chronic myeloid leukemia (CML) is a malignant disease of the hematopoietic system with a key pathogenic protein BCR-ABL, which seriously threatens the lives of patients. The first drug based on the inhibition of the hybrid tyrosine kinase BCR-ABL, the gene of which is located on the "Philadelphia chromosome", was imatinib. Imatinib therapy turned out to be quite successful: patients with CML achieved a complete cytogenic response 2 years after the start of treatment and a state of stable remission for a long time. However, the inevitable resistance to imatinib, which occurs in clinical settings due to mutations in the BCR-ABL kinase, gave impetus to the development of new specific drugs, such as dasatinib, nilotinib, bosutinib and ponatinib. Currently, the pharmaceutical market offers the second and third generations of BCR-ABL tyrosine kinase inhibitors designed to combat mutant BCR-ABL and possessing better selectivity. It is noteworthy that the first allosteric inhibitor that can effectively overcome mutations in the ATP binding site has appeared on the market. In recent years, chimeras aimed at proteolysis (PROTAC) based on another E3 ligand have come into use, as a result of which they are able to overcome drug resistance due to selective degradation of target proteins. Data on inhibitors that have received the status of approved drugs for the treatment of CML are presented. Promising areas for the development of new BCR-ABL inhibitors are indicated. The relevance of this area of research is confirmed by the emergence of a significant number of new publications on this topic.

作者简介

S. Kostryukov

National Research Ogarev Mordovia State University

Email: kostryukov_sg@mail.ru
Russia, Saransk

O. Belyakova

National Research Ogarev Mordovia State University

Russia, Saransk

D. Mishkin

National Research Ogarev Mordovia State University

Russia, Saransk

D. Stulnikov

National Research Ogarev Mordovia State University

Russia, Saransk

A. Dektyarev

National Research Ogarev Mordovia State University

Russia, Saransk

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