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Advances in the study of new BCR-ABL kinase inhibitors
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Wen-yu CUI, Ruo-xi ZHAO, Lu-lu HAN, Wei-wei NI, Fei LI*, Jin-song HAN*
Acta Pharmaceutica Sinica | 2023, 58(2) : 258 - 273
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Acta Pharmaceutica Sinica | 2023, 58(2): 258-273
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Advances in the study of new BCR-ABL kinase inhibitors
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Wen-yu CUI, Ruo-xi ZHAO, Lu-lu HAN, Wei-wei NI, Fei LI*, Jin-song HAN*
Affiliations
  • State Key Laboratory of Natural Medicines and National R & D Center for Chinese Herbal Medicine Processing, Department of Food Quality and Safety, College of Engineering, China Pharmaceutical University, Nanjing 211109, China
Published: 2023-02-12 doi: 10.16438/j.0513-4870.2022-0807
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The oncogenic product of BCR-ABL is an abnormal tyrosine kinase that causes chronic myeloid leukemia (CML). With further research into the pathogenesis of CML, the discovery of compounds that selectively inhibit abnormal BCR-ABL tyrosine kinases is a research focus worthy of attention. The first three generations of BCR-ABL inhibitors are orthosteric inhibitors, which competitively block the binding of ABL protein tyrosine kinase to ATP and prevent it from activating downstream signals. The fourth-generation BCR-ABL inhibitors allosterically inhibit ABL protein tyrosine kinase by binding to the myristoyl pocket, providing greater selectivity and maintaining activity against drug-resistant mutations proteins. Novel drug design strategies such as proteolytic targeting chimera (PROTAC), covalent inhibitors and dual targeting inhibitors also provide new directions for the development of BCR-ABL kinase inhibitors. This paper reviews recent research advances on BCR-ABL kinase inhibitors and discusses drug design strategies for various novel BCR-ABL inhibitors.

chronic myeloid leukemia  /  BCR-ABL  /  inhibitor  /  drug design strategy
Wen-yu CUI, Ruo-xi ZHAO, Lu-lu HAN, Wei-wei NI, Fei LI, Jin-song HAN. Advances in the study of new BCR-ABL kinase inhibitors[J]. Acta Pharmaceutica Sinica, 2023 , 58 (2) : 258 -273 . DOI: 10.16438/j.0513-4870.2022-0807
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Year 2023 volume 58 Issue 2
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doi: 10.16438/j.0513-4870.2022-0807
  • Receive Date：2022-07-04
  • Online Date：2025-11-21
  • Published：2023-02-12
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  • Received：2022-07-04
  • Revised：2022-08-25
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    State Key Laboratory of Natural Medicines and National R & D Center for Chinese Herbal Medicine Processing, Department of Food Quality and Safety, College of Engineering, China Pharmaceutical University, Nanjing 211109, China
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