SKLB4771 (FLT3-IN-1)

Catalog No.S1099 Batch:S109901

Technical Data

Formula	C₂₅H₂₇N₇O₃S₂
Molecular Weight	537.66	CAS No.	1370256-78-2
Solubility (25°C)*	In vitro	DMSO	50 mg/mL (92.99 mM)
		Water	Insoluble
		Ethanol	Insoluble
* <1 mg/ml means slightly soluble or 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. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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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 (from reference)

Cell Assay:^{^[1]}	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.
Animal Study:^{^[1]}	Animal Models female NOD-SCID mouse (6−7 weeks old) Dosages 20 mg/kg, 40 mg/kg, 100 mg/kg Administration IV

Cell Assay:^{^[1]}

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.

Animal Study:^{^[1]}

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

References

[1] Li WW, et al. J Med Chem. 2012 26;55(8):3852-66.

Selleck's SKLB4771 (FLT3-IN-1) has been cited by 1 publication

Atractylenolide-1 Targets FLT3 to Regulate PI3K/AKT/HIF1-α Pathway to Inhibit Osteogenic Differentiation of Human Valve Interstitial Cells [ Front Pharmacol, 2022, 13:899775]	PubMed: 35571096

Atractylenolide-1 Targets FLT3 to Regulate PI3K/AKT/HIF1-α Pathway to Inhibit Osteogenic Differentiation of Human Valve Interstitial Cells [ Front Pharmacol, 2022, 13:899775]

PubMed: 35571096

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