GW 806742X

GW 806742X is an inhibitor of necroptosis.¹ It binds to mixed lineage kinase domain-like protein (Mlkl; K_d = 9.3 µM for the mouse protein), reducing its association with the cytoplasmic membrane, and decreases necroptosis induced by TNF-α, a Smac mimetic, and the caspase inhibitor Q-VD-OPH (Item No. 15260) in isolated mouse dermal fibroblasts when used at a concentration of 500 nM. GW 806742X is also an inhibitor of VEGFR2 (IC₅₀ = 2 nM).² It decreases VEGF-induced proliferation of human umbilical vein endothelial cells (HUVECs; IC₅₀ = 5 nM). GW 806742X (10 µM) inhibits mammosphere formation by, reduces the number of extracellular actin fibers extruding from, and decreases intracellular IL-1β levels in, MDA-MB-231 triple-negative breast cancer cells.³

WARNING This product is not for human or veterinary use.

1. Hildebrand, J.M., Tamzer, M.C., Lucet, I.S., et al. Activation of the pseudokinase MLKL unleashes the four-helix bundle domain to induce membrane localization and necroptotic cell death. Proc. Natl. Acad. Sci. USA 111(42), 15072-15077 (2014).

2. Sammond, D.M., Nailor, K.E., Veal, J.M., et al. Discovery of a novel and potent series of dianilinopyrimidineurea and urea isostere inhibitors of VEGFR2 tyrosine kinase. Bioorg. Med. Chem. Lett. 15(15), 3519-3523 (2005).

3. Song, C., Kendi, A.T., Lowe, V.J., et al. The A20/TNFAIP3-CDC20-CASP1 axis promotes inflammation-mediated metastatic disease in triple-negative breast cancer. Anticancer Res. 42(2), 681-695 (2022).