Abstract
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 interest 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 signaling. 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.
Publication types
-
Research Support, Non-U.S. Gov't
-
Review
MeSH terms
-
Humans
-
Indoles / chemistry
-
Indoles / pharmacology
-
Indoles / therapeutic use
-
Leukemia, Myeloid, Acute / drug therapy
-
Leukemia, Myeloid, Acute / pathology
-
Protein Kinase Inhibitors / chemistry*
-
Protein Kinase Inhibitors / pharmacology
-
Protein Kinase Inhibitors / therapeutic use
-
Pyrazoles / chemistry
-
Pyrazoles / pharmacology
-
Pyrazoles / therapeutic use
-
Pyrimidines / chemistry
-
Pyrimidines / pharmacology
-
Pyrimidines / therapeutic use
-
Signal Transduction / drug effects
-
Small Molecule Libraries / chemistry*
-
Small Molecule Libraries / pharmacology
-
Small Molecule Libraries / therapeutic use
-
Urea / analogs & derivatives
-
Urea / pharmacology
-
Urea / therapeutic use
-
fms-Like Tyrosine Kinase 3 / antagonists & inhibitors*
-
fms-Like Tyrosine Kinase 3 / metabolism
Substances
-
Indoles
-
Protein Kinase Inhibitors
-
Pyrazoles
-
Pyrimidines
-
Small Molecule Libraries
-
Urea
-
fms-Like Tyrosine Kinase 3