BML-286

Uses

BML-286 is a small molecule inhibitor of the PDZ domain of Dishevelled (Dvl): an essential protein in the Wnt signaling pathways. This compound reduced the levels of apoptosis in the hyaloid vessels of the eye and also suppressed the growth of prostate cancer PC-3 cells. It is a useful tool for studies dissecting the Wnt signaling pathways.

Definition

ChEBI: 2-[[oxo-[3-[(1-oxo-2-phenylethyl)amino]phenyl]methyl]amino]benzoic acid is a member of benzamides.

General Description

A cell-permeable amidobenzanilide compound that disrupts Fz-Dvl (frizzled-dishevelled) interaction by targeting the PDZ domain (K_d = 10.6 μM) of Dvl, blocking Wnt3a-induced (10 ng/ml) transcription activity (~50% inhibition at 3 μM in 293 cell SuperTopflash reporter assays) and suppressing the Wnt pathway-dependent growth of prostate cancer PC-3 cells (by 16% in 72 h at ≥50 μM; IC₅₀ = 12.5 μM). Shown to effectively prevent Wnt3A mRNA injection-induced xenopus embryo deformation (effective conc. = 25 μM) and suppress Wnt pathway-mediated apoptosis of the hyaloid vescular endothelial cells in the mouse eyes via vitreous injection (144 fmol/120 nl/eye) in vivo.