FYJ-195
FYJ-195 is a potent orally active FLT3 inhibitor targeting FLT3 and its variants FLT3-ITD, FLT3-F691L, FLT3-D835V, FLT3-D835Y. FYJ-195 blocks FLT3 autophosphorylation and downstream STAT5, AKT, ERK signaling pathways, and induces apoptosis. FYJ-195 induces tumor regression in mouse acute myeloid leukemia (AML) xenograft models. FYJ-195 can be used for the research of AML.
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- Formule: C26H26F3N7O2
- Masse moléculaire:525.53
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Stockage:
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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Activité biologique
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Chemical Information
- Pureté et documentation
- Références
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Help & FAQs
Activité biologique
FYJ-195 potently inhibits FLT3-WT, FLT3-ITD, and drug-resistant FLT3 variants (F691L, D835Y) with IC50 values ≤2.03 nM, while also showing inhibitory activity against a limited subset of other kinases including KDR and JAK1[1].
FYJ-195 potently inhibits the proliferation of FLT3-ITD-driven MOLM-13 and MV4-11 AML cells with IC50 values of 0.80 nM and 0.22 nM, respectively, while showing minimal activity against FLT3-WT, non-FLT3-dependent cancer cells, and normal cells, indicating high on-target selectivity[1].
FYJ-195 potently inhibits the proliferation of BaF3 cells transformed with FLT3-ITD and drug-resistant FLT3 mutations (N676D, D835V, D835Y, F691L) with IC50 values ranging from 0.41 nM to 9.09 nM[1].
FYJ-195 (0.1-100 nM; 24 h) dose-dependently arrests MOLM-13 and MV4-11 AML cells in the G0-G1 phase[1].
FYJ-195 (0.1-100 nM; 24-48 h) dose-dependently induces apoptosis in MOLM-13 and MV4-11 AML cells[1].
FYJ-195 (0.1-100 nM; 2-12 h) dose-dependently inhibits the FLT3-STAT5/AKT/ERK signaling pathway in FLT3-ITD-driven AML cells and FLT3 mutant-transformed BaF3 cells (including drug-resistant F691L and D835V variants), with no effect on signaling in FLT3-independent K562 cells[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MOLM-13, MV4-11 cells
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Concentration:0.1; 1; 10; 100 nM
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Incubation Time:24 h
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Result:Increased the percentage of G0-G1 phase cells in MOLM-13 from 49.7% (vehicle) to 56.0% (0.1 nM), 63.6% (1 nM), 79.4% (10 nM), and 89.6% (100 nM).
Increased the percentage of G0-G1 phase cells in MV4-11 from 53.2% (vehicle) to 54.5% (0.1 nM), 72.9% (1 nM), 85.7% (10 nM), and 92.4% (100 nM).
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Cell Line:MOLM-13, MV4-11 cells
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Concentration:0.1; 1; 10; 100 nM
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Incubation Time:24; 48 h
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Result:Induced apoptosis rates in MOLM-13 of 4.39% (0.1 nM), 9.71% (1 nM), 15.32% (10 nM), and 26.2% (100 nM) after 24 h, and 5.48% (0.1 nM), 14.62% (1 nM), 36.1% (10 nM), and 60.6% (100 nM) after 48 h.
Induced apoptosis rates in MV4-11 of 5.56% (0.1 nM), 13.34% (1 nM), 20.64% (10 nM), and 25.8% (100 nM) after 24 h, and 9.13% (0.1 nM), 19.53% (1 nM), 51.66% (10 nM), and 65.43% (100 nM) after 48 h.
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Cell Line:MOLM-13, MV4-11 cells, BaF3-FLT3-ITD-F691L, BaF3-FLT3-ITD-D835V cells, FLT3-independent K562 cells
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Concentration:0.1; 0.3; 1; 3; 10; 30; 100 nM
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Incubation Time:2 h (MOLM-13/MV4-11); 12 h (BaF3/K562)
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Result:Dose-dependently reduced phosphorylation of FLT3, STAT5, AKT, and ERK in MOLM-13 and MV4-11 cells, with near-complete inhibition observed at 10 nM to 30 nM.
Dose-dependently suppressed p-FLT3 and p-STAT5 in BaF3-FLT3-ITD-F691L and BaF3-FLT3-ITD-D835V cells, with complete inhibition at 100 nM (a concentration where quizartinib showed no significant activity).
Had no effect on phosphorylation of FLT3, STAT5, ERK, or AKT in K562 cells.
| Species | Dose | Route | AUC0-t | AUC0-∞ | C0 | T1/2 | Vz | CL | MRT0-t | MRT0-∞ | Cmax | Tmax | Vz/F | CL/F | F |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Mice[1] | 1 mg/kg | i.v. | 66.9 ng·h/mL | 69.4 ng·h/mL | 347 ng/mL | 0.539 h | 11.3 L/kg | 14.6 L/h/kg | 0.323 h | 0.412 h | / | / | / | / | / |
| Mice[1] | 10 mg/kg | p.o. | 23.6 ng·h/mL | 24.8 ng·h/mL | / | 0.359 h | / | / | 0.547 h | 0.631 h | 28.3 ng/mL | 0.250 h | 246 L/kg | 535 L/h/kg | 3.58 % |
FYJ-195 (10-50 mg/kg; i.p.; daily; 9 days) achieves robust tumor growth suppression in FLT3F691L-resistant mosue AML xenograft model[1].
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 (male, 4-5 weeks old) subcutaneously injected with MV4-11 cells[1]
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Dosage:10; 25; 50 mg/kg
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Administration:i.v.; daily; 14 days
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Result:Induced tumor growth inhibition (TGI) of 125%, 128%, and 130% at 10, 25, and 50 mg/kg, respectively.
Achieved tumor weight inhibition rates (IR) of 90.6%, 97.6%, and 98.7% at 10, 25, and 50 mg/kg, respectively.
Reduced Ki-67 positive cells in a dose-dependent manner in tumor tissues.
Increased TUNEL-positive apoptotic cells in a dose-dependent manner in tumor tissues.
Abrogated p-STAT5 in tumor tissues.
Caused no significant body weight loss or organ pathology across doses.
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Animal Model:BALB/c nude (female, 4-6 weeks old) subcutaneously injected with BaF3-FLT3-ITD-F691L cells[1]
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Dosage:10; 50 mg/kg
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Administration:i.p.; daily; 9 days
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Result:Induced tumor growth inhibition (TGI) of 21.3% at 10 mg/kg and 68.6% at 50 mg/kg.
Achieved tumor weight inhibition rates (IR) of 18% at 10 mg/kg and 61% at 50 mg/kg.
Caused no significant body weight loss in treated mice.
Chemical Information
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Masse moléculaire 525.53
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Formule C26H26F3N7O2
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SMILES
NC1=NOC2=C1C(C3=CC=C(C=C3)NC(NC4=CC(C(F)(F)F)=C(C=C4)CN5CCN(CC5)C)=O)=CC=N2
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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)
FYJ-195 Related Classifications
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