Recent Progress in the Development of Transglutaminase 2 (TGase2) Inhibitors

Transglutaminase 2 (TGase2, TG2) activity has been implicated in the pathogenesis of a number of unrelated disorders, including celiac, neurological, and renal diseases, and various forms of cancer. It has been suggested that TGase2 activity, such as cross-linking, deamidation, and GTP-related activity, is associated with each disease. Continuing efforts to develop small molecule TG2 inhibitors are ongoing. To develop a new class of TG2 inhibitors, the factors impeding the development of TG2 inhibitors have been identified. Additionally, the conformational effect of TG2 enzyme in regard to its pathological roles, in vitro screening methods, recently discovered TG2 inhibitors, and preclinical evaluations are discussed with a brief summary of current TG2 inhibitor pipelines under the clinical setting.