| Identification | Back Directory | [Name]
2H-Indol-2-one, 3-[(3E)-1,3-dihydro-3-[[2-(1-piperazinyl)ethoxy]imino]-2H-indol-2-ylidene]-5-fluoro-1,3-dihydro-, hydrochloride (1:1), (3Z)- | [CAS]
2435562-99-3 | [Synonyms]
FLT3-IN-15
2H-Indol-2-one, 3-[(3E)-1,3-dihydro-3-[[2-(1-piperazinyl)ethoxy]imino]-2H-indol-2-ylidene]-5-fluoro-1,3-dihydro-, hydrochloride (1:1), (3Z)- | [Molecular Formula]
C22H23ClFN5O2 | [MOL File]
2435562-99-3.mol | [Molecular Weight]
443.91 |
| Hazard Information | Back Directory | [Uses]
FLT3-IN-15 is a highly potent and orally active FLT3 inhibitor with IC50s of 0.87 nM and 0.32 nM for FLT3 and FLT3/D835Y, respectively. FLT3-IN-15 can be used for researching acute myeloid leukemia[1]. | [in vivo]
FLT3-IN-15 (20 mg/kg; PO; daily, for 21 days) results in the rapid and complete remission of tumors in all mice[1].
FLT3-IN-15 (2000 mg/kg; PO; single) causes one female mouse died at day 6, and the LD50 value is calculated as 4,950 mg/kg in female mice[1].
FLT3-IN-15 (10 μM) shows 21.4% inhibition of hERG ligand binding[1].
FLT3-IN-15 (10 mg/kg; PO and IV; single) exhibits an AUClast of 25.0 μg·min/mL, a Cmax of 36.5 ng/mL, and a remarkable increase in the oral bioavailability of 42.6%[1].
Pharmacokinetic Parameters of FLT3-IN-15 in male ICR mice[1].
| PO (10 mg/kg) | IV (10 mg/kg) | | AUClast (μg·min/mL) | 25.0 ± 11.6 | 58.5 ± 57.4 | | AUCinf (μg·min/mL) | 62.1 ± 58.6 | 103.4 ± 95.3 | | MRT (hr) | 2811.3 ± 2713.0 | 1257.1 ± 1084.1 | | T1/2 (hr) | 1775.7 ± 1901.0 | 1099.2 ± 945.8 | | CL (mL/min/kg) | | 158.7 ± 98.7 | | VSS (L/kg) | | 127891 ± 104764 | | Cmax (ng/mL) | 36.5 ± 24.3 | | | Tmax (min) | 390.0 ± 366.0 | | | Xu, 24h (%) | 0.001 ± 0.0 | 0.002 ± 0.002 | | GI24h (%) | 0.05 ± 0.05 | 0.24 ± 0.02 | | F (%) | 42.9 | |
| Animal Model: | BALB/c nu/nu (injected with MV4-11)[1] | | Dosage: | 20 mg/kg | | Administration: | PO; daily, for 21 days | | Result: | Resulted in the rapid and complete remission of tumors in all mice, and no weight loss or any other signs of toxicity during the administration period. |
| Animal Model: | Female ICR mice[1] | | Dosage: | 2000 mg/kg | | Administration: | PO; single | | Result: | Caused one female mouse of the 2,000?mg/kg group died at day 6 and the approximate lethal dose (ALD) is determined over 2,000?mg/kg in male mice and 2,000?mg/kg in female mice, respectively; the LD50 value was calculated as 4,950 mg/kg in female mice. |
| Animal Model: | Male ICR mice[1] | | Dosage: | 10 mg/kg | | Administration: | PO and IV; single (Pharmacokinetics Analysis) | | Result: | Exhibited an AUClast of 25.0 μg·min/mL, a Cmax of 36.5 ng/mL, and a remarkable increase in the oral bioavailability of 42.6%. |
| [References]
[1] Jeong P, Moon Y, Lee JH, et al. Discovery of orally active indirubin-3'-oxime derivatives as potent type 1 FLT3 inhibitors for acute myeloid leukemia. Eur J Med Chem. 2020;195:112205. DOI:10.1016/j.ejmech.2020.112205 |
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