Mechanistic studies of PFKFB2 reveals a novel inhibitor of its kinase activity
2024

New Inhibitor of PFKFB2 Kinase Activity Identified

publication Evidence: moderate

Author Information

Author(s): Eyster Craig, Matsuzaki Satoshi, Pranay Atul, Giorgione Jennifer R., Faakye Anna, Ahmed Mostafa, Humphries Kenneth M.

Primary Institution: Cold Spring Harbor Laboratory

Hypothesis

Can a new inhibitor be identified for PFKFB2 kinase activity?

Conclusion

A new inhibitor, B2, was identified that effectively inhibits PFKFB2 and alters glycolytic activity in cells.

Supporting Evidence

  • B2 inhibits PFKFB2 with an IC50 of 3.29 μM.
  • B2 also inhibits PFKFB3 with an IC50 of 11.89 μM.
  • B2 treatment decreased fructose-1,6-bisphosphate levels in A-498 cells.
  • B2 increased fructose-6-phosphate levels, indicating an inhibitory effect on PFK-1 activity.

Takeaway

Scientists found a new substance that stops a specific enzyme from working, which could help in treating diseases like cancer.

Methodology

Recombinant PFKFB2 was expressed and an enzymatic assay was developed to test a library of molecules for inhibition.

Digital Object Identifier (DOI)

10.1101/2024.12.25.630325

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