KAN0438757

Catalog No.S0400

For research use only.

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.

KAN0438757 Chemical Structure

CAS No. 1451255-59-6

Purity & Quality Control

Choose Selective PFKFB Inhibitors

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 Research:

[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 Research:

[2]

  • Animal Models: C57BL6/N mice
  • Dosages: 10, 25, 50 mg/kg
  • Administration: i.p.

Solubility (25°C)

In vitro

Chemical Information

Molecular Weight 447.43
Formula

C21H18FNO7S

CAS No. 1451255-59-6
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles C1=CC(=CC(=C1)S(=O)(=O)NC2=CC(=C(C=C2)C(=O)OCCO)O)C3=C(C=CC(=C3)F)O

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)

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Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )

Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.

Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.

Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such
as vortex, ultrasound or hot water bath can be used to aid dissolving.

Molarity Calculator

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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

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