FLT3/HDAC-IN-3
FLT3/HDAC-IN-3 is a dual inhibitor of FLT3 and HDAC. FLT3/HDAC-IN-3 potently inhibits FLT3 (IC50 = 14 nM), HDAC1 (IC50 = 27 nM), HDAC6 (IC50 = 20 nM), and FLT3D853Y (IC50 = 55 nM), exhibits weak activity against HDAC8, and shows no activity against HDAC4. FLT3/HDAC-IN-3 possesses kinase selectivity, plasma stability, and stability in human liver microsomes. FLT3/HDAC-IN-3 demonstrates anti-proliferative effects in a variety of hematological malignancy cell lines. FLT3/HDAC-IN-3 shows efficacy in the Jeko-1 xenograft model without observed significant toxicity. FLT3/HDAC-IN-3 can be used in the study of hematological malignancies.
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- No. CAS: 2864394-30-7
- Fòrmula: C22H32FN7O2
- Peso molecular:445.53
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Actividad biológica
Descripciòn
IC50 & Target
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FLT3 14 nM (IC50) |
HDAC6 20 nM (IC50) |
HDAC1 27 nM (IC50) |
FLT3D835Y 55 nM (IC50) |
HDAC8 2800 nM (IC50) |
HDAC4 >10000 nM (IC50) |
In Vitro
FLT3/HDAC-IN-3 (compound 6s) (72 h) potently inhibits the proliferation of MV-4-11 cells (IC50 = 29 nM) and Jeko-1 cells (IC50 = 99 nM) with favorable tumor-cell selectivity (IC50 = 80 μM in HaCaT cells)[1].
FLT3/HDAC-IN-3 (0-1000 nM; 72 h) dose-dependently inhibits FLT3 and STAT5 phosphorylation, increases H3Ac levels, and upregulates Bax in MV-4-11 cells[1].
FLT3/HDAC-IN-3 (0-1000 nM; 72 h) induces dose-dependent cell death in MV-4-11 and Jeko-1 cells, and dose-dependently induces ROS accumulation, decreases mitochondrial membrane potential [1].
FLT3/HDAC-IN-3 (0-1000 nM; 48 h or 72 h) induces time- and dose-dependent apoptosis in MV-4-11 and Jeko-1 cells[1].
FLT3/HDAC-IN-3 (0-1000 nM; 72 h) dose-dependently arrests the cell cycle in the G2 phase in MV-4-11 cells[1].
FLT3/HDAC-IN-3 (200 μM; 0–72 h) exhibits good plasma stability in rat plasma, with 67.8% retention after 72 h[1].
FLT3/HDAC-IN-3 shows favorable metabolic stability in human liver microsomes with a half-life of 165 min and intrinsic clearance of 7.56 mL/min/kg[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 cells
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Concentration:0 nM, 50 nM, 250 nM, 1000 nM
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Incubation Time:72 h
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Result:Dose-dependently inhibited phosphorylated FLT3 and p-STAT5; increased acetylated histone H3 (H3Ac) levels in a concentration-dependent manner, with higher H3Ac accumulation at 250 nM compared to SAHA at the same concentration; upregulated pro-apoptotic protein Bax in a dose-dependent manner.
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Cell Line:MV-4-11, Jeko-1 cells
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Concentration:0 nM, 50 nM, 250 nM, 1000 nM
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Incubation Time:72 h
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Result:Induced a dose-dependent increase in red fluorescence (dead cells) and decrease in green fluorescence (live cells) in both MV-4-11 and Jeko-1 cells.
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Cell Line:MV-4-11, Jeko-1 cells
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Concentration:0 nM, 50 nM, 250 nM, 1000 nM
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Incubation Time:48 h or 72 h
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Result:Induced apoptosis in a time- and dose-dependent manner; at 72 h, induced 47.7% apoptosis at 250 nM and up to 75% apoptosis at 1000 nM in MV-4-11 cells, with effects comparable to SAHA + Tandutinib combination treatment; also induced dose-dependent apoptosis in Jeko-1 cells.
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Cell Line:MV-4-11 cells
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Concentration:0 nM, 50 nM, 250 nM, 1000 nM
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Incubation Time:72 h
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Result:Effectively arrested the cell cycle in the G2 phase in a dose-dependent manner
Parmacokinetics
| Species | Dose | Route | T1/2 | Tmax | Cmax | AUC0-t | AUC0-∞ | MRT0-t | MRT0-∞ | F |
|---|---|---|---|---|---|---|---|---|---|---|
| Rat[1] | 5 mg/kg | i.v. | 0.54 h | 0.083 h | 86.00 ng/mL | 48.70 ng·h/mL | 52.20 ng·h/mL | 0.48 h | 0.63 h | / |
| Rat[1] | 30 mg/kg | p.o. | 2.21 h | 0.50 h | 17.80 ng/mL | 33.90 ng·h/mL | 60.90 ng·h/mL | 1.68 h | 4.49 h | 19.50 % |
| Rat[1] | 30 mg/kg | i.p. | 1.14 h | 0.33 h | 137 ng/mL | 148 ng·h/mL | 153 ng·h/mL | 0.96 h | 1.09 h | 49.00 % |
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:NOD/SCID mice injected with Jeko-1 cells[1]
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Dosage:15 mg/kg; 30 mg/kg
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Administration:i.p.; daily; 15 days
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Result:Achieved 37.14% TGI and 0.47 g average tumor weight at 15 mg/kg; achieved 53.34% TGI and 0.39 g average tumor weight at 30 mg/kg.
Induced more severe tumor cell necrosis than control or SAHA groups at 30 mg/kg.
Caused no significant weight loss or abnormalities in drinking, diet, or activity at 30 mg/kg.
Chemical Information
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No. CAS 2864394-30-7
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Peso molecular 445.53
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Fòrmula C22H32FN7O2
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SMILES
FC(C=N1)=C(NCCCCCCC(NO)=O)N=C1NC(C=C2)=CC=C2N3CCN(C)CC3
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
FLT3/HDAC-IN-3 Related Classifications
HY-181086 Related Classifications
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