VA4 – Tranglutaminase 2 Inhibitor small molecule (tool compound)

VA4 is a targeted and irreversible covalent inhibitor of TG2 that locks the enzyme in its open’ conformation in cells

Contributors

Inventor Institute
Jeffrey Keillor University of Ottawa
Cat. #: 159670
Tool sub type: Inhibitor
Research Fields: Cancer
Application: Has been shown to block TG2 transamidation activity inside cancer stem cells (SCC13 cells) resulting in abolished transamidase activity. Inhibitor blocks EMT, invasion and kills cancer stem cells. In mesothiolioma cancer stem cells, inhibition of TG2 reduces migration (invasion), and appears to increase markers of apoptosis.
Purpose: Inhibitor
Alternate name: VA4
Product 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.
Additional notes: Patent: US20190389814, PCT/IB2017/052162
Molecular weight: 635.77
Selectivity: TG2
CAS number: 2088001-23-2
Primary target: Tissue transglutaminase (TG2)
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
Solubility: Soluble in DMSO
References:

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

Related Tools for Small molecules

Cat. # Tool Name
151712 CDK7 inhibitor BS-181 Small Molecule (Tool Compound) Key Info View Tool
151834 Antitumoral Quinol1h Small Molecule (Tool Compound) Key Info View Tool
152625 Mps1 inhibitor CCT251455 Small Molecule (Tool Compound) Key Info View Tool
152786 Nucleolar Luminophore Ag-1 Small Molecule (Tool Compound) Key Info View Tool
153191 CDK inhibitor BS-194 Small Molecule (Tool Compound) Key Info View Tool

Tool enquiry

Please ensure you use your organisation email address rather than personal where possible, as this helps us locate your organisation in our system faster.

Please note we may take up to three days to respond to your enquiry.

CancerTools.org uses the contact information provided to respond to you about our research tools and service. For more information please review our privacy policy.