ZED-1227 (TAK-227) is an orally active, selective and potent transglutaminase 2 (TG2) inhibitor with anticancer activity that blocks inflammation-induced TG2 expression and activation for the treatment of Celiac Disease.

TGase 2:45 nM

ZED-1227, at concentrations ranging from 0.1 μM to 1 μM for 24 hours, does not impact metabolic activity and proliferation in Huh7 cells and CaCo2 cells. This lack of effect suggests that ZED-1227 does not exhibit cytotoxic activity[1].
In an in vitro setting, ZED-1227, when applied at concentrations between 0.002 and 0.2 mg/mL for 30 minutes, inhibits transglutaminase 2 (TG2) in the small intestinal mucosa[1].

In mice, ZED-1227 reduces the activity of intestinal TG2 induced by Polyinosinic:Polycytidylic acid (40 mg/kg) to levels comparable to normal control levels. Additionally, ZED-1227 administration subdues intestinal inflammation in these mice[1].Furthermore, when administered orally (5 mg/kg; i.g.), ZED-1227 is effective in inhibiting TG2 in the small intestinal mucosa[1].