The recent advance of PROTACs targeting BCR-ABL for the treatment of chronic myeloid leukemia

Abstract

The chronic myeloid leukemia is a malignant hematopoietic disorder in which the BCR-ABL kinase has been identified as the causative protein. The inhibitors targeting BCR-ABL kinase have been extensively employed in clinical management of chronic myeloid leukemia, significantly enhancing survival rates and prognosis for patients. Despite the extensive utilization of 1st to 4th generation BCR-ABL inhibitors in clinical therapy, the emergence of drug-resistant mutations necessitates an urgent quest for novel therapeutic strategies. The proteolysis targeting chimera technology represents an innovative strategy for protein degradation, directly degrading BCR-ABL fusion proteins while circumventing challenges associated with drug resistance. This review article provides an overview of current research progress on inhibitors and proteolysis targeting chimeras for the treatment of chronic myeloid leukemia through targeting BCR-ABL. We anticipate that this timely and comprehensive review will serve as a source of inspiration and guidance for pharmaceutical chemists in the development of highly potent BCR-ABL inhibitors and proteolysis targeting chimeras.

Keywords: BCR-ABL inhibitor; Chronic myeloid leukemia; Drug resistance; Protein degradation; Proteolysis targeting chimera.