Identification of a new membrane-permeable inhibitor against inositol-1,4,5-trisphosphate-3-kinase A

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Updated: May 8, 2026

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry
08:07

Identification of Inositol Phosphate or Phosphoinositide Interacting Proteins by Affinity Chromatography Coupled to Western Blot or Mass Spectrometry

Published on: July 26, 2019

Dominik Schröder1, Christoph Rehbach, Carola Seyffarth

  • 1Institut für Biochemie und Signaltransduktion, UKE Hamburg, Martinistr. 52, 20246 Hamburg, Germany.

Biochemical and Biophysical Research Communications
|August 29, 2013
PubMed

Insights

Researchers identified BAMB-4, a cell-permeable inhibitor targeting the inositol-1,4,5-trisphosphate 3-kinase A (ITPKA) enzyme. This discovery offers a potential strategy to reduce lung cancer cell metastasis by blocking ITPKA

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Oncology

Background:

  • Ectopic expression of neuron-specific inositol-1,4,5-trisphosphate-3-kinase A (ITPKA) in lung cancer cells enhances their metastatic potential.
  • ITPKA possesses dual actin-regulating activities: actin filament bundling and phosphorylation of inositol-1,4,5-trisphosphate (InsP3), modulating calcium signals.

Purpose of the Study:

  • To identify specific, membrane-permeable inhibitors of ITPKA's InsP3kinase activity.
  • To block both actin bundling and InsP3kinase activities of ITPKA to inhibit lung cancer metastasis.

Main Methods:

  • High-throughput screening of 341,44 small molecules to identify InsP3kinase inhibitors.
  • Characterization of top compounds (EPPC-3, BAMB-4, MEPTT-3) based on IC50 values, specificity, and hydrophobicity.
  • Cellular uptake, stability, and inhibitor type determination for BAMB-4 in H1299 lung cancer cells.

Main Results:

  • 237 out of 341,44 compounds (0.7%) showed potential as InsP3kinase inhibitors.
  • BAMB-4 demonstrated high membrane permeability, cellular uptake, and stability in H1299 cells.
  • BAMB-4 was identified as a mixed-type inhibitor of ITPKA's InsP3kinase activity.

Conclusions:

  • BAMB-4 is the first identified highly membrane-permeable inhibitor of ITPKA's InsP3kinase activity.
  • This inhibitor provides a novel therapeutic avenue to partially mitigate the metastasis-promoting effects of ITPKA in lung tumors.
Keywords:
Cellular uptakeHigh-throughput screeningITPKAITPKA-inhibitorInsP(3)MetastasisMixed inhibition type

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