KCC009

KCC009 is an inhibitor of transglutaminase 2 (TG2; K_i = 0.068 mM).¹ It reduces radiation-induced increases in the expression of TGM2, the gene encoding TG2, in wild-type H1299 and p53-mutant H1299 (H1299/M175H-p53) cells when used at a concentration of 3.91 µM.² KCC009 sensitizes wild-type H1299 and H1299/M175H-p53 cells to radiation and induces cell cycle arrest at the G₀/G₁ and G₂/M phases, respectively. It inhibits fibronectin remodeling in U87MG glioblastoma cells when used at a concentration of 1 mM.³ KCC009 (50 mg/kg) sensitizes tumors to N,N’-bis(2-chloroethyl)-N-nitrosourea (carmustine; Item No. 15775) and increases survival in an orthotopic mouse model of DBT-FG glioblastoma when administered in combination with N,N’-bis(2-chloroethyl)-N-nitrosourea. It also reverses warfarin-induced arterial calcification in rats and prevents relapse in a rat model of experimental autoimmune encephalomyelitis (EAE).^4,5

WARNING This product is not for human or veterinary use.

1. Watts, R.E., Siegel, M., and Khosla, C. Structure-activity relationship analysis of the selective inhibition of transglutaminase 2 by dihydroisoxazoles. J. Med. Chem. 49(25), 7493-7501 (2006).

2. Huaying, S., Dong, Y., Chihong, Z., et al. Transglutaminase 2 inhibitor KCC009 induces p53-independent radiosensitization in lung adenocarcinoma cells. Med. Sci. Monit. 22, 5041-5048 (2016).

3. Yuan, L., Siegel, M., Choi, K., et al. Transglutaminase 2 inhibitor, KCC009, disrupts fibronectin assembly in the extracellular matrix and sensitizes orthotopic glioblastomas to chemotherapy. Oncogene 26(18), 2563-2573 (2007).

4. Beazley, K.E., Banyard, D., Lima, F., et al. Transglutaminase inhibitors attenuate vascular calcification in a preclinical model. Arterioscler. Thromb. Vasc. Biol. 33(1), 43-51 (2012).

5. van Strien, M.E., de Vries, H.E., Chrobok, N.L., et al. Tissue transglutaminase contributes to experimental multiple sclerosis pathogenesis and clinical outcome by promoting macrophage migration. Brain Behav. Immun. 50, 141-154 (2015).