Table 3 Oxindole-based FLT3 inhibitors
Compound name and its structure | Description | Refs. | |
|---|---|---|---|
| Target | FLT3, c- KIT, PDGFR-ẞ, and VEGFDR2 | |
Binding mode to FLT3 kinase | Type I | ||
Mutation point | A848P, A627P, F691L, and Y842C | ||
FLT3 Potency (IC50) | 50, and 250Â nM (FLT3-ITD (in MV4-16 cells), and FLT3-wt (in RS4-16 cells), respectively) | ||
In vitro targeted AML cells (IC50) | 8 and 15Â nM (in MV4-16 expressing FLT3-ITD, and OC1-AML5 cells expressing FLT3-wt, respectively) | ||
| Target | FLT3-wt, FLT3-D835Y, and FLT3-D835H | [81] |
Binding mode to FLT3 kinase | Type I | ||
FLT3 Potency (IC50) | 40, 8, and 4Â nM, respectively | ||
In vitro targeted AML cells (IC50) | 40Â nM (HCD-57; murine erythropoietin dependent erythroleukemia cells) expressing FLT3-ITD, FLT3- D835Y, and FLT3-D835H) | ||
| Target | FLT3, FLT3-ITD, and FLT3-D835Y | [82] |
Binding mode to FLT3 kinase | Type I | ||
FLT3 Potency (IC50) | 5.3, 0.7, and 2.7Â nM, respectively | ||
In vitro targeted AML cells (IC50) | 24.8, 5.9, and 5.5Â nM (MV4-16, FLT-ITD- MV4-16, and MOLM-18, respectively) | ||
| Target | FLT3-ITD | [83] |
FLT3-ITD Potency (IC50) | 1.25 μM and17.5 μM (with % inhibition 90.9, ≥ 100.0, respectively) | ||
In vitro targeted AML cells (IC50) | 2.2 μM (MV4-16) | ||
| Target | FLT3-ITD- D835H, FLT3-ITD- F691L, and FLT3-D835H | [84] |
Binding mode to FLT3 kinase | Type I | ||
FLT3 Potency (IC50) | 0.83, 1.5, and 1.3Â nM | ||
| Target | wt-FLT3, FLT3-ITD, and FLT3/D835Y | [85] |
Binding mode to FLT3 kinase | Type I | ||
FLT3 Potency (IC50) | 0.87, 0.25, and 0.32Â nM | ||
In vitro targeted AML cells (IC50) | 1.0Â nM | ||
| Target | FLT3, FLT3-ITD, and FLT3-D835Y | [86] |
Binding mode to FLT3 kinase | Type II | ||
FLT3 Potency (IC50) | 1.8, 0.8, and 1.9Â nM, respectively | ||
In vitro targeted AML cells (IC50) | 23.5Â nM (FLT3-ITD- MV4-16), and 35.5Â nM (MOLM-18) | ||
| Target | FLT3, CDK-2, EGFR, and VEGFR-2 (KDR) | [87] |
Binding mode to FLT3 kinase | Type II | ||
FLT3 Potency (IC50) | 0.546 µM | ||
In vitro targeted cancer cells (IC50) | 3.56 µM (MCF-7) | ||
| Target | FLT3, PDGFRα, VEGFR-2 (KDR), Aurora A and B | [88] |
Binding mode to FLT3 kinase | Type I | ||
FLT3 Potency (IC50) | 74.85, 24.15, 46.65, 16.83, and 29.38Â nM, respectively | ||
In vitro targeted AML cells (IC50) | 6.84 and 2.97 µM (CCRF-CEM, and SR leukemia cells, respectively) | ||
| Target | FLT3-ITD | [89] |
FLT3 Potency (IC50) | 2.49 μM | ||
In vitro targeted AML cells (IC50) | 4.3 and 8.7 μM (FLT-ITD- MV4-16, and FLT3-wt-THP-1cells, respectively) | ||
