FLC-8
FLC-8 is an orally active FLT3 inhibitor with IC50 values of 10.2 nM, 11.6 nM and 24.10 nM against human FLT3-WT, FLT3-G697R and FLT3-N676D, respectively. FLC-8 inhibits FLT3 autophosphorylation and downstream STAT5, AKT and ERK signaling pathways, and induces apoptosis in acute myeloid leukemia (AML) cells. FLC-8 exhibits potent antitumor activity in the MV4-11 xenograft model. FLC-8 can be used for the research of acute myeloid leukemia.
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- CAS 番号: 3100242-36-9
- 分子式: C24H19F3N6O3
- 分子量:496.44
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保管条件:
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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生物活性
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STAT5 |
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FLC-8 (3.5 h) potently inhibits FLT3-WT kinase activity with an IC50 of 10.2 nM[1].
FLC-8 (50 μM; 24 h) covalently binds to FLT3 kinase domain at the Cys807 residue[1].
FLC-8 (72 h) potently inhibits MV4-11 and MOLM-13 cell proliferation with IC50 values of 0.28 nM and 2.45 nM, respectively[1].
FLC-8 (72 h) potently inhibits proliferation of BaF3-FLT3ITD, BaF3-FLT3ITD-G697R, and BaF3-FLT3ITD-N676D cells with IC50 values of 3.10 nM, 11.6 nM, and 24.10 nM respectively, while showing reduced activity against other FLT3 mutant BaF3 cell lines[1].
FLC-8 (1 μM) demonstrates a narrow kinome inhibition spectrum with an S10 score of 0.096, potently inhibiting FLT3-WT, FLT3-ITD, PDGFRα, NCOA4-RET, and RET L730I at 1 μM[1].
FLC-8 (0.1-100 nM; 24 h) induces dose-dependent G0-G1 phase arrest in MV4-11 and MOLM-13 AML cells after 24 h incubation[1].
FLC-8 (0.1-100 nM; 24-72 h) induces dose-dependent apoptosis in MV4-11 and MOLM-13 AML cells over 24, 48, and 72 h[1].
FLC-8 (0.1-30 nM) induces apoptosis in MV4-11 cells via activation of the intrinsic apoptotic pathway, as shown by upregulation of pro-apoptotic genes/proteins, downregulation of anti-apoptotic BCL-2, cleavage of caspase-3 and PARP, and DNA fragmentation detected by TUNEL staining[1].
FLC-8 (0.1-30 nM; 12 h) inhibits FLT3 autophosphorylation and downstream STAT5, AKT, and ERK phosphorylation in a dose-dependent manner in MV4-11 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 AML 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:Induced dose-dependent G0-G1 phase arrest in both cell lines.
Increased the G0-G1 population in MOLM-13 cells to 86.4% (from 52.0% in control) at 100 nM.
Increased the G0-G1 population in MV4-11 cells to 48.9%, 57.5%, 80.1%, and 87.0% at 0.1, 1, 10, and 100 nM respectively.
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Cell Line:MV4-11 and MOLM-13 AML cells
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Concentration:0.1, 1, 10, 100 nM
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Incubation Time:24, 48, 72 h
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Result:Induced dose-dependent apoptosis in both cell lines.
In MOLM-13 cells, apoptosis rates were 7.91-21.60% (24 h), 3.89-45.52% (48 h), and 3.69-73.90% (72 h).
In MV4-11 cells, apoptosis rates were 7.69-19.11% (24 h), 13.33-46.9% (48 h), and 7.61-71.20% (72 h).
Exceeded 70% apoptosis rates in both cell lines at 100 nM and 72 h.
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Cell Line:MV4-11 AML cells
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Concentration:0.1, 0.3, 1.0, 3.0, 10, 30 nM
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Incubation Time:12 h
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Result:Potently inhibited FLT3 autophosphorylation in a dose-dependent manner, with significant suppression at 10 nM.
Reduced phosphorylation levels of STAT5, AKT, and ERK in a concentration-dependent fashion.
Exhibited superior inhibition of FLT3-mediated signaling at 30 nM compared to Quizartinib (HY-13001).
FLC-8 (10-50 mg/kg; p.o., i.p.; daily; 14 days) exhibits modest, dose-dependent antitumor activity against BaF3-FLT3-ITD-G697R AML xenografts, with the highest efficacy (TGI = 32%) achieved at an oral dose of 50 mg/kg[1].
FLC-8 (1-10 μM; immersion; 24 hours) demonstrates a favorable hematopoietic safety profile in transgenic zebrafish, with no significant impairment of neutrophil production at concentrations up to 10 μM[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 (female, 4-5 weeks old, 18-20 g, subcutaneous inoculation of MV4-11 FLT3-ITD-expressing cells)[1]
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Dosage:10 mg/kg; 25 mg/kg; 50 mg/kg
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Administration:i.p.; daily; 14 days
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Result:Elicited dose-dependent tumor growth inhibition with TGI values of 136%, 163%, and 178% at 10, 25, and 50 mg/kg, respectively.
Achieved inhibitory rates (IR) based on final tumor weight of 25.0%, 48.2%, and 78.6% at 10, 25, and 50 mg/kg, respectively.
Induced dose-dependent tumor cell necrosis, reduced Ki67 staining, increased TUNEL staining, and reduced phosphorylated STAT5 in tumor tissues.
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Animal Model:Balb/c nude (female, 6-8 weeks old, 18-20 g, subcutaneous inoculation of BaF3-FLT3-ITD-G697R cells)[1]
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Dosage:10 mg/kg (p.o.); 50 mg/kg (p.o.); 10 mg/kg (i.p.)
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Administration:p.o. (daily; 14 days); i.p. (daily; 14 days)
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Result:Produced minimal tumor growth inhibition (TGI = 2%) with a tumor weight inhibitory rate of 13.4% at oral 10 mg/kg.
Improved efficacy to a TGI of 32% with a tumor weight inhibitory rate of 30.7% at oral 50 mg/kg.
Resulted in a TGI of 11% with a tumor weight inhibitory rate of 8.5% at intraperitoneal 10 mg/kg.
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Animal Model:Eze-Rinka (3-4 months old)[1]
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Dosage:1 μM; 10 μM
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Administration:immersion; 24 hours
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Result:Did not significantly reduce neutrophil counts at either concentration when compared to the vehicle control group.
化学情報
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CAS 番号 3100242-36-9
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分子量 496.44
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分子式 C24H19F3N6O3
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SMILES
C=CC(NC1=C(C(F)(F)F)C=C(NC(NC2=CC=C(C3=C(C(N)=NO4)C4=NC(C)=C3)C=C2)=O)C=C1)=O
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
純度とドキュメンテーション
参考文献
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
FLC-8 関連分類
HY-182937 関連分類
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