Title:The Progress of Small Molecule Targeting BCR-ABL in the Treatment of
Chronic Myeloid Leukemia
Volume: 24
Issue: 6
Author(s): Yuan Zhang, Xin Wu, Xueyan Sun, Jun Yang, Chang Liu, Guotao Tang, Xiaoyong Lei, Honglin Huang and Junmei Peng*
Affiliation:
- Department of Pharmacy, School of Pharmacy, Hengyang Medical School, Institute of Pharmacy and Pharmacology,
Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China,
Hengyang, Hunan, 421001, China
Keywords:
CML, BCR-ABL protein, tyrosine kinase inhibitors, proteolysis-targeting chimeric, T315I mutation, molecular docking.
Abstract: Chronic myelogenous leukemia (CML) is a malignant myeloproliferative disease. According
to the American Cancer Society's 2021 cancer data report, new cases of CML account for
about 15% of all leukemias. CML is generally divided into three stages: chronic phase, accelerated
phase, and blast phase. Nearly 90% of patients are diagnosed as a chronic phase. Allogeneic stem
cell transplantation and chemotherapeutic drugs, such as interferon IFN-α were used as the earliest
treatments for CML. However, they could generate obvious side effects, and scientists had to seek
new treatments for CML. A new era of targeted therapy for CML began with the introduction of
imatinib, the first-generation BCR-ABL kinase inhibitor. However, the ensuing drug resistance and
mutant strains led by T315I limited the further use of imatinib. With the continuous advancement of
research, tyrosine kinase inhibitors (TKI) and BCR-ABL protein degraders with novel structures
and therapeutic mechanisms have been discovered. From biological macromolecules to classical
target protein inhibitors, a growing number of compounds are being developed to treat chronic myelogenous
leukemia. In this review, we focus on summarizing the current situation of a series of candidate
small-molecule drugs in CML therapy, including TKIs and BCR-ABL protein degrader. The
examples provided herein describe the pharmacology activity of small-molecule drugs. These drugs
will provide new enlightenment for future treatment directions.
