Small-molecule Fms-like Tyrosine Kinase 3 Inhibitors: An Attractive and Efficient Method for the Treatment of Acute Myeloid Leukemia

Yue Zhong, Run-Ze Qiu, Shan-Liang Sun, Chao Zhao, Tianyuan Fan, Min Chen, Nianguang Li, Zhi-Hao Shi
Journal of Medicinal Chemistry 2020 July 13
Fms-like tyrosine kinase 3 (FLT3) is an important member of the class III receptor tyrosine kinase (RTK) family, which is involved in the proliferation of hematopoietic cells and lymphocytes. In recent years, increasing evidence have demonstrated that the activation and mutation of FLT3 is closely implicated in the occurrence and development of acute myeloid leukemia (AML). The exploration of small-molecule inhibitors targeting FLT3 has aroused wide interests of pharmaceutical chemists and is expected to bring new hope for AML therapy. In this review, we specifically highlighted FLT3 mediated JAK/STAT, RAS/MAPK and PI3K/AKT/mTOR signalling. The structural properties and biological activities of representative FLT3 inhibitors reported from 2014 to the present were also summarized. In addition, the major challenges in the current advance of novel FLT3 inhibitors were further analyzed, with the aim to guide future drug discovery.

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