Advances in the study of new BCR-ABL kinase inhibitors
10.16438/j.0513-4870.2022-0807
- VernacularTitle:新型BCR-ABL激酶抑制剂的研究进展
- Author:
Wen-yu CUI
;
Ruo-xi ZHAO
;
Lu-lu HAN
;
Wei-wei NI
;
Fei LI
;
Jin-song HAN
- Publication Type:Research Article
- Keywords:
chronic myeloid leukemia;
BCR-ABL;
inhibitor;
rug design strategy
- From:
Acta Pharmaceutica Sinica
2023;58(2):258-273
- CountryChina
- Language:Chinese
-
Abstract:
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.
