PROTAC FLT-3 degrader 5
PROTAC FLT-3 degrader 5 is an orally active FLT3 PROTAC degrader with a DC50 of 1.2 nM. PROTAC FLT-3 degrader 5 also acts as a molecular glue to degrade GSPT1 and IKZF1/3, with DC50 values of 8.54 nM, 0.02 nM and 0.79 nM, respectively. PROTAC FLT-3 degrader 5 mediates the degradation of FLT3, GSPT1 and IKZF1/3 through interaction with the cereblon E3 ubiquitin ligase complex. PROTAC FLT-3 degrader 5 can be used in the research of acute myeloid leukemia.
(Pink: FLT3 ligand (HY-169374); Blue: Cereblon ligand (HY-14658); Black: linker).
For research use only. We do not sell to patients.
- Formula: C46H59N11O7
- Molecular Weight:878.03
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
FLT3 1.2 nM (DC50) |
IKZF1 0.02 nM (DC50) |
IKZF3 0.79 nM (DC50) |
eRF3a/GSPT1 8.54 nM (DC50) |
Cereblon |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| MV4-11 | IC50 |
1.67 nM
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Antiproliferative activity against human FLT3-ITD mutant MV-4-11 acute myeloid leukemia cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay.
Antiproliferative activity against human FLT3-ITD mutant MV-4-11 acute myeloid leukemia cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay.
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40578254 |
| MOLM-13 | IC50 |
3.16 nM
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Antiproliferative activity against human FLT3-ITD mutant MOLM-13 acute myeloid leukemia cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay.
Antiproliferative activity against human FLT3-ITD mutant MOLM-13 acute myeloid leukemia cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay.
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40578254 |
| THP-1 | IC50 |
>1000 nM
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Antiproliferative activity against human FLT3 wild-type THP-1 acute myeloid leukemia cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay.
Antiproliferative activity against human FLT3 wild-type THP-1 acute myeloid leukemia cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay.
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40578254 |
| MV4-11 | IC50 |
4.74 nM
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Antiproliferative activity against human FLT3-ITD-F691L mutant transformed MV-4-11 acute myeloid leukemia cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay.
Antiproliferative activity against human FLT3-ITD-F691L mutant transformed MV-4-11 acute myeloid leukemia cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay.
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40578254 |
| MV4-11 | IC50 |
3.70 nM
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Antiproliferative activity against human FLT3-ITD-D835Y mutant transformed MV-4-11 acute myeloid leukemia cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay.
Antiproliferative activity against human FLT3-ITD-D835Y mutant transformed MV-4-11 acute myeloid leukemia cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay.
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40578254 |
| MOLM-13 | IC50 |
5.61 nM
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Antiproliferative activity against human FLT3-ITD-F691L mutant transformed MOLM-13 acute myeloid leukemia cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay.
Antiproliferative activity against human FLT3-ITD-F691L mutant transformed MOLM-13 acute myeloid leukemia cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay.
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40578254 |
| MOLM-13 | IC50 |
7.55 nM
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Antiproliferative activity against human FLT3-ITD-D835Y mutant transformed MOLM-13 acute myeloid leukemia cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay.
Antiproliferative activity against human FLT3-ITD-D835Y mutant transformed MOLM-13 acute myeloid leukemia cells assessed as reduction in cell viability incubated for 72 hrs by CCK-8 assay.
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40578254 |
| MV4-11 | DC50 |
1.2 nM
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FLT3 protein degradation activity in human MV-4-11 acute myeloid leukemia cells measured after 24 hrs incubation by western blotting.
FLT3 protein degradation activity in human MV-4-11 acute myeloid leukemia cells measured after 24 hrs incubation by western blotting.
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40578254 |
In Vitro
PROTAC FLT-3 degrader 5 (Compound A2) (72 h) potently inhibits the proliferation of MV-4-11 and MOLM-13 acute myeloid leukemia cells harboring the FLT3-ITD mutation, with IC50 values of 1.67 nM and 3.16 nM, respectively, and exerts no significant inhibitory effect on the proliferation of FLT3 wild-type THP-1 acute myeloid leukemia cells[1].
PROTAC FLT-3 degrader 5 (72 h) exhibits significant antiproliferative activity that overcomes drug resistance in MV-4-11 and MOLM-13 resistant cells expressing FLT3-ITD-F691L and FLT3-ITD-D835Y mutations, with IC50 values of 4.74 nM, 3.70 nM, 5.61 nM, and 7.55 nM, respectively[1].
PROTAC FLT-3 degrader 5 (1.5-100 nM; 24 h) exerts dose-dependent degradation effects on FLT3, GSPT1, IKZF1 and IKZF3 proteins in MV-4-11 and MOLM-13 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MV-4-11 and MOLM-13
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Concentration:1.5, 3.1, 6.2, 12.5, 25, 50, 100 nM
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Incubation Time:24 h
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Result:Degraded FLT3 protein in a concentration-dependent manner and exhibited a typical PROTAC hook effect at concentrations above 25 nM.
Acted as a molecular glue and significantly degraded CRBN neo-substrates GSPT1, IKZF1, and IKZF3 in a concentration-dependent manner.
Parmacokinetics
Chemical Information
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Molecular Weight 878.03
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Formula C46H59N11O7
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SMILES
O=C1N(C2CCC(NC2=O)=O)C(C3=C1C=CC(N(C4)CCC4CN5CCN(C(CC6)CCN6C(C=C7)=C(OC)C=C7NC8=NC(NC9CCOCC9)=C(CC)N=C8C(N)=O)CC5)=C3)=O
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
PROTAC FLT-3 degrader 5 Related Classifications
HY-175040 Related Classifications
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