Table 2.
Summary of the antibodies targeting FLT3 and small molecules targeting FLT3 expression that have been developed and in clinical trialsa.
| Class | Antibody/Small molecule | In-vivo/In-vitro model | Clinical Trial ID | Phase | Reference |
|---|---|---|---|---|---|
|
| |||||
| monoclonal antibody | IMC-EB10 | Yes/Yes | NCT00887926 | I | (Piloto et al., 2005) |
| IMC-NC7 | Yes/Yes | (Piloto et al., 2005) | |||
| Fc-optimized antibody | BV10SDIEM | Yes/Yes | NCT02789254 | I/II | (Hofmann et al., 2012) |
| 4G8SDIEM (FLYSYN) | Yes/Yes | (Hofmann et al., 2012) | |||
| scFv-ELP fusion protein | a-FLT3-A192 | Yes/Yes | (Park et al., 2020) | ||
| FLT3 bispecific antibody | 4G8 X UCHT1 | No/Yes | (Durben et al., 2015) | ||
| Anti-FLT3-CD3 immunoglobulin G (IgG)-based bispecific antibody | 7370 Anti-FLT3-CD3 | Yes/Yes | (Yeung et al., 2020) | ||
| FLT3 targeted CART Cell | anti-FLT3-scFv-CD28-CD3ζ | Yes/Yes | NCT03904069 | I | (Chen et al., 2017) |
| FLT3 CAR-T AMG 553 | Yes/Yes | ||||
| FLT3 Ligand-based CART Cell | FLT3L CAR-T | Yes/Yes | (Wang et al., 2018) | ||
| Yes/Yes | (Jetani, Garcia-Cadenas, Nerreter, Goetz, 2018, Jetani, Garcia-Cadenas, Nerreter, Thomas, 2018) | ||||
| Maternal embryonic leucine zipperkinase (MELK) inhibitors |
aOTS167
|
Yes/Yes | NCT02795520 | I/II | (Eisfelder et al., 2021) |
| Natural compound inhibitor of eIF4A |
aSilvestrol
|
Yes/Yes | (Alachkar et al., 2013) | ||
| NEDD8-activating enzyme inhibitor |
aMLN4924 (Pevonedistat)
|
Yes/Yes |
NCT00911066
NCT03268954 NCT02610777 NCT02782468 NCT04266795 NCT03772925 NCT04090736 NCT03013998 |
I III II I II I III I/II |
(Swords et al., 2015) |
| T-LAK cell-originated protein kinase (TOPK) |
aOTS514
|
Yes/Yes | (Alachkar et al., 2015) | ||
| Dual FLT3/TOPK inhibitor |
aHSD1169
|
No/Yes | (Dayal et al., 2018) | ||
| Deubiquitinating enzyme (USP10) |
aHBX19818
|
Yes/Yes | (Weisberg et al., 2017) | ||
| Inhibitor |
aP22077
|
||||
References of 2D structures in Table 2.
1. Dayal, N., Opoku-Temeng, C., Hernandez, D. E., Sooreshjani, M. A., Carter-Cooper, B. A., Lapidus, R. G., & Sintim, H. O. (2018). Dual FLT3/TOPK inhibitor with activity against FLT3-ITD secondary mutations potently inhibits acute myeloid leukemia cell lines. Future Med Chem, 10, 823–835. https://doi.org/10.4155/fmc-2017-0298.
2. PubChem Identifier: CID 11787114 (Silvestrol)
3. PubChem Identifier: CID 135398499 (Otssp167)
4. PubChem Identifier: CID 16720766 (Pevonedistat)
5. PubChem Identifier: CID 46931953 (P22077)
6. PubChem Identifier: CID 73349008 (HBX19818)
7. PubChem Identifier: CID 92044487 (OTS514 hydrochloride)