FI-700
FI-700 is an orally active FLT3 inhibitor with an IC50 of 20 nM. FI-700 induces G1 phase cell cycle arrest by inhibiting autophosphorylation of mutant FLT3 and the downstream STAT5/MAPK pathway. FI-700 triggers the mitochondrial apoptosis pathway by downregulating anti-apoptotic proteins Mcl-1 and Bcl-XL, altering the conformation of Bax, and activating caspase-3. FI-700 can be used in research related to acute myeloid leukemia.
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- CAS No.: 866883-79-6
- Formule: C21H29N9O
- Masse moléculaire:423.51
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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
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Activité biologique
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STAT5 |
Mcl-1 |
Caspase-3 |
Bcl-xL |
Bax |
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| MV4-11 | IC50 |
0.014 μM
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Antiproliferative activity against human leukemia MV4;11 (FLT3/ITD) cells assessed as reduction in cell viability incubated for 72 hrs by CellTiter96 Proliferation Assay.
Antiproliferative activity against human leukemia MV4;11 (FLT3/ITD) cells assessed as reduction in cell viability incubated for 72 hrs by CellTiter96 Proliferation Assay.
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17671144 |
| MOLM-13 | IC50 |
0.016 μM
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Antiproliferative activity against human leukemia MOLM13 (FLT3/ITD) cells assessed as reduction in cell viability incubated for 72 hrs by CellTiter96 Proliferation Assay.
Antiproliferative activity against human leukemia MOLM13 (FLT3/ITD) cells assessed as reduction in cell viability incubated for 72 hrs by CellTiter96 Proliferation Assay.
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17671144 |
| Kasumi 1 | IC50 |
0.18 μM
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Antiproliferative activity against human leukemia Kasumi-1 (c-KIT mutation) cells assessed as reduction in cell viability incubated for 72 hrs by CellTiter96 Proliferation Assay.
Antiproliferative activity against human leukemia Kasumi-1 (c-KIT mutation) cells assessed as reduction in cell viability incubated for 72 hrs by CellTiter96 Proliferation Assay.
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17671144 |
| THP-1 | IC50 |
3.1 μM
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Antiproliferative activity against human leukemia THP1 (Wt-FLT3) cells assessed as reduction in cell viability incubated for 72 hrs by CellTiter96 Proliferation Assay.
Antiproliferative activity against human leukemia THP1 (Wt-FLT3) cells assessed as reduction in cell viability incubated for 72 hrs by CellTiter96 Proliferation Assay.
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17671144 |
| HL-60 | IC50 |
6.8 μM
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Antiproliferative activity against human leukemia HL60 (no FLT3) cells assessed as reduction in cell viability incubated for 72 hrs by CellTiter96 Proliferation Assay.
Antiproliferative activity against human leukemia HL60 (no FLT3) cells assessed as reduction in cell viability incubated for 72 hrs by CellTiter96 Proliferation Assay.
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17671144 |
| K562 | IC50 |
5.2 μmol/L
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Antiproliferative activity against human leukemia K562 (BCR/ABL) cells assessed as reduction in cell viability incubated for 72 hrs by CellTiter96 Proliferation Assay.
Antiproliferative activity against human leukemia K562 (BCR/ABL) cells assessed as reduction in cell viability incubated for 72 hrs by CellTiter96 Proliferation Assay.
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17671144 |
| MEG-01 | IC50 |
6.1 μM
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Antiproliferative activity against human leukemia MegO1 (BCR/ABL) cells assessed as reduction in cell viability incubated for 72 hrs by CellTiter96 Proliferation Assay.
Antiproliferative activity against human leukemia MegO1 (BCR/ABL) cells assessed as reduction in cell viability incubated for 72 hrs by CellTiter96 Proliferation Assay.
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17671144 |
FI-700 (0.01-0.1 μM; 72 h) selectively inhibits the growth of mutant FLT3 cells in human leukemia cell lines (MV4;11, MOLM-13, THP1, Kasumi-1, K562)[1].
FI-700 (0.03-1.0 μM; 6 h) inhibits constitutive phosphorylation of FLT3, STAT5 and MAPK in MOLM-13 cells[1].
FI-700 (100 nM; 48 h) selectively reduces the growth of primary human AML cells harboring FLT3/ITD or FLT3/D835Y mutations[1].
FI-700 (0.01-0.3 μM; 24 h) induces G1-phase cell cycle arrest and increases the population of sub-G1 apoptotic cells in MOLM-13 cells[1].
FI-700 (200-800 nM; 24-72 h) induces apoptosis, reduces Mcl-1 and Bcl-XL expression, induces Bax conformational changes, and activates caspase-3 in MOLM-13 cells[2].
FI-700 potently inhibits the activity of recombinant human FLT3 kinase with an IC50 of 20 nM, and exhibits relative selectivity against other tyrosine kinases as well as serine/threonine kinases[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, MOLM-13, THP1, Kasumi-1, HL60, K562, MegO1, and 32D transfectants
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Concentration:0.01, 0.03, 0.05, 0.1 μM
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Incubation Time:72 h
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Result:Specifically inhibited the growth of leukemia cell lines carrying FLT3/ITD or FLT3/D835Y mutations, while showing lower sensitivity against cell lines expressing wild-type FLT3 or lacking FLT3.
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Cell Line:MOLM-13 cells
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Concentration:0.03, 0.1, 0.3, 1.0 μM
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Incubation Time:6 h
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Result:Dose-dependently inhibited the constitutive autophosphorylation of the target kinase, and concurrently down-regulated the phosphorylation levels of downstream STAT5 and MAPK signals.
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Cell Line:MOLM-13 cells
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Concentration:0.010, 0.030, 0.100, 0.300 μM
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Incubation Time:24 h
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Result:Led to an increase in the proportion of cells in the G1 phase and a reciprocal reduction in the S-G2 phase, significantly inducing the appearance of sub-G1 apoptotic cell populations at higher concentrations.
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Cell Line:Primary human AML cells
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Concentration:100 nM
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Incubation Time:48 h
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Result:Significantly reduced the number of primary cells carrying mutations, but did not affect the growth of wild-type cells.
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Cell Line:MOLM-13 cells
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Concentration:200, 400, 800 nM
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Incubation Time:72 h
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Result:Significantly induced apoptosis in leukemia cells, although this apoptosis-inducing effect was partially attenuated in a co-culture system with mesenchymal stromal cells (MSCs).
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Cell Line:MOLM-13 cells
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Concentration:800 nM
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Incubation Time:24 h
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Result:Led to decreased expression levels of anti-apoptotic proteins Mcl-1 and Bcl-XL, and triggered Bax conformational activation and caspase-3 cleavage activation.
FI-700 (200 mg/kg; p.o.; twice daily for 5 consecutive days; survival monitored up to day 60) significantly prolongs the survival of mice in the intravenous MOLM-13 xenograft mouse model[1].
FI-700 (200 mg/kg; p.o.; twice daily; for 4 consecutive days; sacrificed on day 13) exerts effects of eliminating leukemia cells in peripheral blood and bone marrow without inducing severe myelosuppression in a syngeneic transplanted C3H/Hej mouse model[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:SCID (Fox Chase C.B-17/Icr-scidJcl, male, 5 weeks old, s.c. inoculation of MOLM-13 FLT3/ITD-positive leukemia cells, prior i.p. anti-asialo-GM1 antibody treatment)[1]
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Dosage:100 mg/kg; 200 mg/kg
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Administration:p.o.; b.i.d.; 5 days; for 5 days
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Result:Significantly induced the regression of subcutaneous tumors in a dose-dependent manner.
Caused no significant body weight loss or mortality during the entire treatment course.
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Animal Model:SCID (Fox Chase C.B-17/Icr-scidJcl, male, 5 weeks old, i.v. inoculation of MOLM-13 FLT3/ITD-positive leukemia cells, prior i.p. anti-asialo-GM1 antibody treatment)[1]
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Dosage:200 mg/kg
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Administration:p.o.; b.i.d.; 5 days
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Result:Significantly prolonged the survival time of the leukemia-bearing mice compared to the conventional chemotherapeutic drug Ara-C treatment.
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Animal Model:C3H/Hej (i.v. inoculation of FLT3/ITD-GFP-32D leukemia cells)[1]
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Dosage:200 mg/kg
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Administration:p.o.; b.i.d.; 4 days
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Result:Significantly repressed the expansion of leukemia cells in the peripheral blood and bone marrow.
Resulted in significantly less bone marrow suppression (total bone marrow cell counts remained normal) and lighter spleen weight compared to standard chemotherapy (Ara-C).
Chemical Information
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CAS No. 866883-79-6
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Masse moléculaire 423.51
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Formule C21H29N9O
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SMILES
CCCNC1=NC(NCCC2=CC=NC=C2)=NC=C1C3=NN=C(CN4CCNCC4)O3
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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)
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