GK921 is an inhibitor of transglutaminase 2 (TGase).

TGase 2:8.93 μM

GK921 inhibits TGase 2-induced polymerization of I-κBα and p53 in a dose-dependent manner. The cytotoxicity of GK921 ranged from a GI50 of 10^-10 to 10^-4 M with an average GI50 of 9.05×10^-7 M. GK921 rescues p53 levels and consequently induces apoptosis, increasing c-PARP and p53 levels in a concentration-dependent manner[1].'

A single treatment with GK921 significantly stabilizes p53 and nearly completely reduces tumor growth in the ACHN and CAKI-1 preclinical xenograft tumor models, suggesting a potential new therapeutic approach to RCC[1].

TGase 2 from guinea pig liver is preincubated for 10 min with various concentrations of GK13 or GK921 in 0.1 mL of reaction buffer, with or without 10 mM CaCl2, followed by the addition of 0.4 mL of substrate solution containing 2

Cells are transfected with a BAX promoter luciferase reporter construct. After exposure to GK921 (0, 0.5, 1, 2.5, 5 μM), firefly and Renilla luciferase activities are measured using a dual luciferase assay kit and pRL-CMV as an internal control[1].