Table 4 Indazole-based FLT3 inhibitors
Compound name and its structure | Description | Refs. | |
|---|---|---|---|
| Target | FLT-3, VEGFR2 (KDR), and PDGFR-β | |
Binding mode to FLT3 kinase | Type II | ||
FLT3 Potency (IC50) | 4, 4, and 66Â nM, respectively | ||
In vitro targeted AML cells (IC50) | 0.69 μM (MV4-16) | ||
| Target | c- Kit, PDGFR-ẞ, and FLT3 | [101] |
Clinical development | In vivo xenograft Studied | ||
FLT3 Potency (IC50) | 68.5, 150, and 375Â nM, respectively | ||
In vitro targeted AML cells (IC50) | 1.17, 1.34, and 1.77 μM (SK-MEL-3, NB-4, and SK-MEL-31 cancer cells, respectively) | ||
| Target | FLT3 | [102] |
Binding mode to FLT3 kinase | Type I | ||
FLT3 Potency (IC50) | 9Â nM | ||
In vitro targeted AML cells (IC50) | 174Â nM (FLT3-ITD- MV4-16) | ||
| Target | FLT3, D835H-FLT3, D835Y-FLT3, ITD-FLT3, K663Q-FLT3, N841I-FLT3, KIT, and PDGFR | [103] |
Binding mode to FLT3 kinase | Type II | ||
Residual control percentage (%ctrl) versus protein kinases | 0.15, 0.05, 0.1, and 0.05% (FLT3, D835H-FLT3, ITD-FLT3, and KIT, respectively) | ||
In vitro targeted AML cells (IC50) | 5, 16, and 198Â nM (FLT3-MOLM18, PDGFRa-T674M-Ba/F3, and Kit-T670I-Ba/F3 cells, respectively) | ||
| Target | (DYRK1-a, AMPK-a1, and RSK-1 (moderator for the anti-apoptotic purpose of FLT3-ITD in AML cells) | [104] |
Residual control percentage (%ctrl) versus protein kinases | 4, 4, and 8%, respectively | ||
In vitro targeted AML cells (IC50) | From 2 to 3 μM/L (Molm-18, heterozygous FLT3-ITD, and homozygous FLT3-ITD-MV4-16 cells) | ||
