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Contributor Information

  • Name Jeffrey Keillor
  • Institute University of Ottawa

Tool Details

  • Tool name: VA4 - Tranglutaminase 2 Inhibitor small molecule (tool compound)
  • Alternate names: VA4
  • Molecular formula: C33H41N5O6S
  • Tool type: Small molecules
  • Tool sub-type: Inhibitor
  • Purpose: Inhibitor
  • Cancer type: Colon
  • Description: Transglutaminases are a family of enzymes that are responsible for mediating the formation of protein crosslinks of several diverse structural proteins (including fibronectin and collagen) through a transamidation reaction between peptide Gln and Lys residues. Tissue transglutaminase (TG2) is a member of this protein family, and is ubiquitously expressed in tissues, primarily found in the cytosol, but is also expressed in the nucleus, membranes, cell surface and extracellularly. TG2 is also able to adopt a compact, or closed conformation which results in minimal crosslinking activity but an increase in its GTP-binding function which affects several cellular signalling pathways. Unregulated transamidation activity is associated with diseases such as fibrosis, atherosclerosis, and celiac disease, while unregulated GTP-binding activity has been implicated with cancer cell proliferation, metastasis and aggressive tumours that are resistant to conventional therapeutic intervention. Studies have shown that TG2's GTP-binding activity is essential to the survival of several cancer cell lines, while its transamidation activity is not. VA4 is a targeted and irreversible covalent inhibitor of TG2 that locks the enzyme in its open' conformation in cells, abolishing its GTP-binding activity. In cellular tests, it has been shown to be selective for TG2 over other transglutaminases.
  • Research area: Cancer

  • For Research Use Only

Target Details

  • Target: Tissue transglutaminase (TG2)

Application Details

Handling

  • Purity: 635.77g/mol
  • Solubility: Soluble in DMSO
  • Storage conditions: Dry, dark and at 0 - 4°C for short term (days to weeks) or -20°C for long term (months to years). Aliquot to avoid freeze-thaw cycles. Lasts up to 3 years with proper storage
  • Shipping conditions: Dry Ice

Documentation

  • Available on request

References

  •   Akbar et al. 2017. J Med Chem. 60(18):7910-7927. PMID: 28858494.