KAN0438757

Catalog No.S0400 Batch:S040001

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Technical Data

Formula

C21H18FNO7S
Molecular Weight 447.43 CAS No. 1451255-59-6
Solubility (25°C)* In vitro DMSO 7 mg/mL (15.64 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.)

Preparing Stock Solutions

Biological Activity

Description KAN0438757 is a potent and selective inhibitor of the metabolic kinase PFKFB3 (6-Phosphofructo-2-Kinase/Fructose-2,6-Biphosphatase 3) with IC50 of 0.19 μM and 3.6 μM for PFKFB3 and PFKFB4, respectively.
Targets
PFKFB3 [1]
(Cell-free assay)		 PFKFB4 [1]
(Cell-free assay)
0.19 μM 3.6 μM
In vitro

A PFKFB3 inhibitor, KAN0438757, which selectively inhibits proliferation of transformed cells while sparing non-transformed cells. Inhibition of PFKFB3 enzymatic activity by KAN0438757 impairs IR-induced recruitment of ribonucleotide reductase (RNR) M2 and deoxynucleotide incorporation upon DNA repair.[1]
In vivo

In vivo administration of KAN0438757 in mice is well tolerated and does not trigger major systemic or toxic alterations.[2]

Protocol (from reference)

Kinase Assay:

[1]
  • ADP-GloTM Kinase Assay

    First, after the kinase reaction, an equal volume of ADP-GloTM Reagent was added to terminate the kinase reaction and deplete the remaining ATP. Second, the Kinase Detection Reagent was added to simultaneously convert ADP to ATP and allow the newly synthesized ATP to be measured using a luciferase/luciferin reaction. The light generated was measured. The assay was performed in white 384-well plates by consecutive additions of a test compound solution, enzyme solution and substrate. Controls in the absence of inhibitor, 100 nM of an in-house inhibitor, and 49.5 µM of an in-house inhibitor were included in the plate. The final concentrations of all reagents per well were 50 mM Tris HCl at pH 8.0, 10 mM MgCl2, 5 mM NaPi at pH 8.0, 81.48 nM PFKFB3 or 145 nM PFKFB4, 8 µM ATP, 100 µM F6P (acid treated and then neutralized to remove any contaminating F-2,6-P2), 0.005% Tween-20 and 1 mM dithiothreitol. Enzyme, compounds, and controls were pre-incubated at room temperature for 15 min before the addition of substrate solution. The enzymatic reaction was allowed to proceed for 20 min and the reaction was terminated by the addition of ADP-GloTM Reagent (10 µL) to all wells followed by 40 min incubation at room temperature. After addition of Kinase Detection Reagent (20 µL) to all wells, the plate was incubated for 30 min at room temperature, followed by measurement. All plates were centrifuged after each addition.
Cell Assay:

[1]
  • Cell lines

    U2OS cells

  • Concentrations

    10 μM

  • Incubation Time

    6 h

  • Method

    Confocal analysis of IR-induced foci of RAD51 or RPA32 in U2OS cells following treatment with DMSO or 10 μM KAN757 (6 h), subjected to IR (6 Gy, 2 h recovery), or left untreated. HR activity after treatment of U2OS DR-GFP cells with indicated inhibitors as assessed by FACS analysis.
Animal Study:

[2]
  • Animal Models

    C57BL6/N mice

  • Dosages

    10, 25, 50 mg/kg

  • Administration

    i.p.

Selleck's KAN0438757 has been cited by 2 publications

Protein Kinase Signaling Networks Driven by Oncogenic Gq/11 in Uveal Melanoma Identified by Phosphoproteomic and Bioinformatic Analyses [ Mol Cell Proteomics, 2023, 22(11):100649] PubMed: 37730182
Protein Kinase Signaling Networks Driven by Oncogenic Gq/11 in Uveal Melanoma Identified by Phosphoproteomic and Bioinformatic Analyses [ Mol Cell Proteomics, 2023, 10.1016/j.mcpro.2023.100649] PubMed: 37730182

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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