| Identification | Back Directory | [Name]
2H-Indol-2-one, 3-[(3E)-1,3-dihydro-3-[[2-oxo-2-(1-piperazinyl)ethoxy]imino]-2H-indol-2-ylidene]-1,3-dihydro-, (3Z)- | [CAS]
2648799-49-7 | [Synonyms]
FLT3/D835Y-IN-1
2H-Indol-2-one, 3-[(3E)-1,3-dihydro-3-[[2-oxo-2-(1-piperazinyl)ethoxy]imino]-2H-indol-2-ylidene]-1,3-dihydro-, (3Z)- | [Molecular Formula]
C22H21N5O3 | [MOL File]
2648799-49-7.mol | [Molecular Weight]
403.43 |
| Hazard Information | Back Directory | [Uses]
FLT3/D835Y-IN-1 (compound 13a) is a orally active, potent and selective FLT3 and FLT3/D835Y inhibitor, with IC50 values of 0.26 nM and 0.18 nM, respectively. FLT3/D835Y-IN-1 also blocks tumor growth, has anticancer efficacy, and can be used to research for AML (acute myeloid leukemia)[1]. | [in vivo]
FLT3/D835Y-IN-1 (10 mg/kg, IP, daily, 6 days per week) significantly suppresses tumor growth and exhibits potent antitumor activity against MOLM14-ITD/D835Y cells[1].
FLT3/D835Y-IN-1 (10 mg/kg, IV or Orally, single) displays extremely low AUC and high clearance[1].
Pharmacokinetic Parameters of FLT3/D835Y-IN-1 in ICR mice[1].
| Parameters | 13a | | AUClast (ng*h/mL) | 1360 ± 110 | | CL (L/h/kg) | 6.96 ± 0.66 | | Vss (L/kg) | 14.8 ± 0.7 | | T1/2 (h) | 1.5 ± 0.1 |
| Animal Model: | NOD/SCID mice (6 weeks, male, nine mice per group)[1] | | Dosage: | 10 mg/kg | | Administration: | IP, daily, 6 days per week, from day 7 to day 29 | | Result: | Significantly suppressed tumor growth. |
| Animal Model: | ICR mice (7–8 weeks, male)[1] | | Dosage: | 10 mg/kg, dissolved in a solution (10% DMSO, 40% PEG400, and 50% PBS) | | Administration: | IV or Orally, single (Pharmacokinetic Analysis) | | Result: | Displayed extremely low AUC and high clearance. |
| [IC 50]
FLT3/D835Y: 0.18 nM (IC50) | [References]
[1] Lee JH, Shin JE, Kim W, et al. Discovery of indirubin-3'-aminooxy-acetamide derivatives as potent and selective FLT3/D835Y mutant kinase inhibitors for acute myeloid leukemia. Eur J Med Chem. 2022 Apr 21;237:114356. DOI:10.1016/j.ejmech.2022.114356 |
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