Compounds AA9 (Z015), NC9 (Z016) and VA4 (Z017), were developed and produced by Dr. Jeffrey Keillor, Department of Chemistry and Biomolecular Sciences, University of Ottawa, Canada. The mechanism-based blockers carry an irreversible acting acrylamide warhead linked to a lysine side chain. Especially the NC9 and VA4 compounds are valuable tools shown to lock TG2 in the open conformation in vitro and in living cells, and to abolish GTP binding. Further, the molecules halt the proliferation and invasion of cancer stem cells. Find more details in the respective PDS.
The “Keillor TG2 Inhibitors” bear an acrylamide warhead, being attacked by the active site cysteine residue (1) to form an irreversible complex (2,3).