SKLB4771 (FLT3-IN-1)

For research use only.

Catalog No.S1099

SKLB4771 (FLT3-IN-1) Chemical Structure

CAS No. 1370256-78-2

SKLB4771 is a potent and selective inhibitor of human receptor-type tyrosine-protein kinase FLT3 with IC50 of 10 nM.

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Biological Activity

Description SKLB4771 is a potent and selective inhibitor of human receptor-type tyrosine-protein kinase FLT3 with IC50 of 10 nM.
Targets
FLT3 [1]
(Cell-free assay)
10 nM
In vitro

SKLB4771 just weakly inhibits Aurora A, FMS, FLT4, and c-Kit (IC50s: 1.5 μM, 2.8 μM, 3.7 μM, and 6.8 μM, respectively). SKLB4771 displays almost no inhibitory activity against the other 13 selected protein kinases. SKLB4771 potently inhibits the growth of MV4-11 cells that express FLT3-ITD, with an IC50 value of 0.006 μM. SKLB4771 just exhibits very weak inhibitory activity against human T lymphoma Jurkat cells, human Burkitt’s lymphoma Ramos cells, human lung cancer PC-9 and H292 cells, and human epithelial carcinoma A431 cells (IC50: 3.05 μM, 6.25 μM, 3.72 μM, 6.94 μM, and 8.91 μM, respectively).[1].

In vivo

Treatment with SKLB4771 at 100 mg/ kg/d results in rapid and complete tumor regression in all mice of this group in the MV4-11 xenograft model. SKLB4771 treatment at 20 mg/kg/d and 40 mg/kg/d significantly slows down the tumor growth, the tumor inhibition rates are 66% and 84%,respectively. Moreover, during the whole experiment, no significant weight loss or any other obvious signs of toxicity are observed for all of the SKLB4771-treated mice. The tumor tissues from the SKLB4771-treated groups show significantly fewer Ki67(tumor mitotic index)-positive cells. The TUNEL data shows an obvious increase in the percentage of apoptotic cells in a time-dependent manner.[1]

Protocol

Cell Research:

[1]

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  • Cell lines: MV4−11, K562, U937, Jurkat, Ramos, Karpas299, HCC827, A549, H2228, H820, PC-9, H292, MDA-MB-231, BT474, MCF-7, HCT116, SW480, LoVo, HeLa, SKOV-3, SK, DU145, PC-3, A431, SH-SY5Y
  • Concentrations: increasing concentrations
  • Incubation Time: 72 h
  • Method:

    The leukemia cells are seeded in a 96-well plate at 1−4 × 104 cells per well, and an equal volume of medium containing increasing concentrations of inhibitors is added to each well. At the end of the incubation period (72 h at 37 °C), 20 μL of 5 mg/mL MTT reagent is added per well for 2−4 h of incubation, and 50 μL of 20% acidified SDS per well is used to lyse the cells. The other cell lines are seeded in 96-well plates at a density of 2−5 × 103 cells/well for 24 h followed by replacement of the medium with serial dilutions of inhibitors in culture medium. Following a 72-h incubation, the MTT reagent is added for a 2−4-h incubation, and 100% DMSO is used to dissolve the cells.


    (Only for Reference)
Animal Research:

[1]

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  • Animal Models: female NOD-SCID mouse (6−7 weeks old)
  • Dosages: 20 mg/kg, 40 mg/kg, 100 mg/kg
  • Administration: IV
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 50 mg/mL (92.99 mM)
Water Insoluble
Ethanol Insoluble

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 537.66
Formula

C25H27N7O3S2

CAS No. 1370256-78-2
Storage powder
in solvent
Synonyms N/A
Smiles CC1=CC=C(C=C1)NC(=O)NC2=NN=C(S2)SC3=NC=NC4=C3C=CC(=C4)OCCCN5CCOCC5

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

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FLT3 Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID