MA191
MA191 is a FLT3 PROTAC degrader. MA191 abrogates FLT3 inhibitor resistance from rebound activation of mitogen-activated kinases. MA191 mediates rapid FLT3-ITD degradation through a mechanism requiring VHL, neddylation, and BIM. MA191 reduces FLT3-ITD levels before inducing apoptosis. MA191 halts AML cell proliferation in Danio rerio. MA191 can be used for the study of acute myeloid leukemia (AML) (Pink: FLT3 ligand: (HY-175311), Blue: E3 ligase CRBN Ligand (HY-112078), Black: Linker, E3 ligase ligand-linker conjugate (HY-175312)).
(Pink: FLT3 Target protein ligand; Blue: VHL ligand (HY-112078); Black: linker).
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- Formule: C57H73N11O9S
- Masse moléculaire:1088.32
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
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Activité biologique
MA191 (0-100 nM, 24-72 h) inhibits the growth of MV4-11 and MOLM-13 cells with IC50 values between 9.6 and 11 nM[1].
MA191 (50 nM, 6-24 h) inhibits autophosphorylation of FLT3 (pY591) and phosphorylation of ERK1/ERK2, STAT5 and AKT in MV4-11 and MOLM-13 cells[1].
MA191 (10-50 nM, 16-24 h) decreases FLT3-ITD and HSP110 dose- and time-dependently in MV4-11 cells[1].
MA191 (0-100 nM, 6-24 h treatment) induces BIM-dependent and neddylation-dependent degradation of FLT3-ITD in MV4-11 cells, demonstrating DC50 values of 10.5 nM at 16 h and 10 nM at 24 h[1].
MA191 (0-1000 nM, 24-48 h) induces apoptosis of cultured and primary AML cells with FLT3-ITD and does not affect normal immune cells, hematopoietic stem cells, and progenitor cells[1].
MA191 (50-200 nM, 24-72 h) breaks mechanisms of FLT3 inhibitor resistance of AML cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MV4-11 and MOLM-13 cells
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Concentration:50 nM
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Incubation Time:6, 24 h
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Result:Inhibited the autophosphorylation of FLT3 (pY591) and phosphorylation of ERK1/ERK2, STAT5 and AKT.
Decreased the FLT3-ITD levels after 24 h, whereas in RS4-11, FLT3 was less affected.
Increased the level of caspase-3.
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Cell Line:MV4-11 cells, BIM-KD-MV4-11 cells and VHL-KD-MV4-11 cells
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Concentration:10, 20, 50 nM
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Incubation Time:6, 16, 24 h
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Result:Degraded FLT3-ITD in MV4-11 cells which was inhibited in BIM-KD-MV4-11 cells.
Degraded HSP110, HSP70, HSP27, and HSP90.
Inhibited the phosphorylation of FLT3-ITD.
Attenuated phosphorylated STAT5 dose- and time-dependently.
Showed a time- and dose-dependent accumulation of active caspase-3 and BIM-EL after 16 h.
Rescued the degradation of FLT3 in cells with a KD of VHL.
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Cell Line:MV4-11 and MOLM-13 cells
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Concentration:100, 200 nM
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Incubation Time:24, 72 h
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Result:Did not induce apoptosis in RS4-11 after a 72-h treatment. In MV4-11 cell cultures, the death rate was nearly 100% and in the case of MOLM-13 cell cultures it was 50%.
Induced cell death in MOLM-13, MOLM-13-RES and MOLM-13-RES-AC.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:MV4-11 cells at density of 1×106 cells/mL were injected into the yolk sac of zebrafish wild-type AB line embryos on day 2 post fertilization[1].
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Dosage:200 nM
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Administration:48 h
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Result:Halted AML cell proliferation.
Showed no significant toxicity .
Chemical Information
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Masse moléculaire 1088.32
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Formule C57H73N11O9S
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SMILES
[H]N([C@@H](C)C1=CC=C(C2=C(C)N=CS2)C=C1)C([C@@H]3C[C@@H](O)CN3C([C@H](C(C)(C)C)NC([C@@H]4CC[C@H](C(N5CCN(CCNC(C6=CC(OC7=CC=C(NC(NC8=NOC(C(C)(C)C)=C8)=O)C=C7)=CC=N6)=O)CC5)=O)CC4)=O)=O)=O
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
MA191 Related Classifications
HY-175273 Related Classifications
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