ISM7594
ISM7594 is an orally active FGFR2/3 inhibitor. ISM7594 shows broad-spectrum antiproliferative potency in FGFR2- or FGFR3-altered cancer cell panels, including FGFR2/3 amplification, fusion, and mutation (BaF3-TEL-FGFR2-V564F (IC50 = 0.067 nM), BaF3-TEL-FGFR2-V564I (IC50 = 2 nM)) types. ISM7594 inhibits tumor growth in a dose-dependent manner. ISM7594 can be used for the study of advanced solid tumors with FGFR2/3 aberrations.
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- No. CAS: 3025799-76-9
- Fòrmula: C29H22F2N6O3
- Peso molecular:540.52
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
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Chemical Information
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Actividad biológica
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FGFR1 118.4 nM (IC50) |
FGFR2 1.7 nM (IC50) |
FGFR3 12.4 nM (IC50) |
FGFR4 3066 nM (IC50) |
ISM7594 (0.01-1000 nM) exhibits markedly superior inhibitory activities against FGFR2 (IC50 = 1.7 nM) and FGFR3 (IC50 = 12.4 nM) compared to the benchmark RE1[1]. ISM7594 (0.01-1000 nM) shows strong inhibitory activity against multiple FGFR2 mutants (V564I (IC50 = 4.4 nM), V564F (IC50 = 0.22 nM))[1]. ISM7594 demonstrates a higher epithelial permeability and a lower efflux ratio in the Caco-2 assay[1]. ISM7594 (0.152-1000 nM, 2 h) effectively suppresses the phosphorylation of FGFR and ERK in gastric adenocarcinoma (SNU-16) and bladder carcinoma (RT4) cells[1]. ISM7594 (10 μM, 72 h) demonstrates potent antiproliferative activity against in the gatekeeper mutant FGFR2/3 in BaF3 cells (BaF3-TEL-FGFR2 (IC50 = 0.17 nM), BaF3-TEL-FGFR3 (IC50 = 14 nM), BaF3-FGFR3-TACC (IC50 = 81 nM), BaF3-TEL-FGFR2-V564F (IC50 = 0.067 nM), BaF3-TEL-FGFR2-V564I (IC50 = 2 nM), BaF3-FGFR3-TACC3-G370C-K650E (IC50 = 34.7 nM)), gastric cancer cells (KATO-III (IC50 = 3.97 nM), SNU-16 (IC50 = 1.6 nM), SNU1 (IC50 = 3.69 nM)), breast cancer cells (SUM52PE (IC50 = 5.5 nM), MCF-7 (IC50 = 8.77 μM)), endometrial cancer cells (AN3CA (IC50 = 7.18 nM), MFE280 (IC50 = 73.7 nM)), bladder cancer cells (RT112-84 (IC50 = 19.8 nM), RT4 (IC50 = 13.9 nM), UM-UC-14 (IC50 = 71 nM), T24 (IC50 = 5.86 μM), UM-UC-3 (IC50 = 8.21 μM)), multiple myeloma (OPM-2 (IC50 = 81.6 nM), U266 (IC50 = 5.28 μM)) and liver cancer (Li-7 (IC50 = 2.34 μM))[1]. ISM7594 (1000 nM) selectively inhibits FGFR1, achieving a 92.9% inhibition rate[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:SNU-16 and RT4 cells
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Concentration:0, 0.152, 0.457, 1.372, 4.115, 12.34, 37.0, 111, 333, 1000 nM
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Incubation Time:2 h
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Result:Suppressed the phosphorylation of FGFR (IC50 = 1.5 nM) and the phosphorylation of ERK (IC50 = 2.1 nM) in SNU-16 cells.
Suppressed the phosphorylation of ERK (IC50 = 22 nM) in RT4 cells.
| Species | Dose | Route | Clearance (CL) | Vd | MRT | Cmax | AUC0-24 | T1/2 | F |
|---|---|---|---|---|---|---|---|---|---|
| Dog[1] | 1 mg/kg | i.v. | 14.7 mL/min/kg | 1.1 L/kg | 1.2 h | / | / | / | / |
| Dog[1] | 5 mg/kg | p.o. | / | / | / | 772 ng/mL | 3022 μg/mL·h | 2.8 h | 54.2 % |
| Mice[1] | 10 mg/kg | p.o. | 39.3 mL/min/kg | 1.1 L/kg | / | 2559 ng/mL | 3945 ng/L.h | / | 91.9 % |
| Rat[1] | 1 mg/kg | i.v. | 74.3 mL/min/kg | 0.79 L/kg | 0.18 h | / | / | / | / |
| Rat[1] | 10 mg/kg | p.o. | / | / | / | 528 ng/mL | 1280 ng/L.h | 1 h | 50.5 % |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:SNU-16 cells (10 million)-derived subcutaneous xenograft female Balb/c nude mice [1]
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Dosage:3, 10, 30 mg/kg
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Administration:i.g. once or twice daily for 21 days
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Result:Inhibited tumor growth in a dose-dependent manner without body weight loss or signs of toxicity.
Demonstrated significant p-FGFR2 suppression and moderate p-AKT suppression.
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Animal Model:RT4 cells (10 million)-derived subcutaneous xenograft female Balb/c nude mice[1]
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Dosage:3, 10, 30 mg/kg
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Administration:i.g. once or twice daily for 21 days
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Result:Inhibited tumor growth in a dose-dependent manner without body weight loss or signs of toxicity.
Chemical Information
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No. CAS 3025799-76-9
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Peso molecular 540.52
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Fòrmula C29H22F2N6O3
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SMILES
C=C(C(NC1=CC=C(C=C1)C2=C(C3=CC=C(C(F)=C3)OC4=NC=CC(C)=N4)C(C(N)=O)=C5C=C(C=NN52)C)=O)F
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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)
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