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

In vivo (Add solvents to the product individually and in order)

Homogeneous suspension

CMC-NA

≥5mg/ml

Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.

* <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.)

Preparing Stock Solutions

Biological Activity

Description

SKLB4771 (FLT3-IN-1) is a potent and selective inhibitor of human receptor-type tyrosine-protein kinase FLT3 with an IC50 of 10 nM.

Targets

FLT3 ^[1]
(Cell-free assay)

10 nM

In vitro

SKLB4771 (FLT3-IN-1) 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). It displays almost no inhibitory activity against the other 13 selected protein kinases. This compound potently inhibits the growth of MV4-11 cells that express FLT3-ITD, with an IC50 value of 0.006 μM. It 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)..

In vivo

In the MV4-11 xenograft model, treatment with SKLB4771 (FLT3-IN-1) at 100 mg/kg/d results in rapid and complete tumor regression in all mice of this group. At doses of 20 mg/kg/d and 40 mg/kg/d, it significantly slows down tumor growth, with inhibition rates of 66% and 84%, respectively. Throughout the experiment, no significant weight loss or other obvious signs of toxicity were observed in any of the treated mice. Tumor tissues from groups receiving this compound showed significantly fewer Ki67 (tumor mitotic index)-positive cells. TUNEL data indicated a time-dependent increase in the percentage of apoptotic cells.

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 SKLB4771 (FLT3-IN-1) is evaluated by seeding leukemia cells in a 96-well plate at 1–4 × 10⁴ cells per well, with an equal volume of medium containing increasing concentrations of this compound 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 the inhibitor 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
SKLB4771 (FLT3-IN-1) is evaluated by seeding leukemia cells in a 96-well plate at 1–4 × 10⁴ cells per well, with an equal volume of medium containing increasing concentrations of this compound 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 the inhibitor 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

https://pubmed.ncbi.nlm.nih.gov/22452518/

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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SHIPPING AND STORAGE
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