ZDON

ZDON (also known as Z-DON or Z006) is a cell-permeable, peptide-based, irreversible inhibitor of tissue transglutaminase 2 (TGM2, TG2) with an IC50 of approximately 150 nM for recombinant TG2. Discovered by Zedira, ZDON mimics gluten peptides with a 6-diazo-5-oxo-norleucine (DON) core, which reacts with the active site cysteine (Cys277) of TG2 to form a stable thioether adduct. It is widely used as a chemical biology research tool to study the role of TG2 in various pathological processes, including celiac disease, Huntington's disease, glioblastoma, and liver/renal fibrosis. Due to the high reactivity and potential toxicity of the DON warhead, ZDON has not been advanced into clinical trials, but it served as a structural starting point for the development of clinical-stage TG2 inhibitors like ZED1227.

Other names

Z-DONZ-DON-Val-Pro-Leu-OMeZ-QVPLbenzyloxycarbonyl-(6-diazo-5-oxonorleucinyl)-L-valinyl-L-prolinyl-L-leucine methyl ester