LFW273 is a specific, orally bioavailable small molecule inhibitor of zinc-finger transcription factor Snail with binding Kd of 1.7 uM, inhibits CREB-binding protein (CBP)-Snail interaction with Kd of 7.3 uM in MST assays.
LFW273 reduces the binding of Snail with CBP in a dose-dependent manner in streptavidin pull-down assay.
LFW273 inhibits Snail expression at the protein but not the mRNA level in a dose-dependent manner in cultured murine embryonic vascular endothelial cells (ECs), substantially reduces secreted CCL5 and CXCL10.
LFW273 markedly suppresses the migration capacity of THP-1 monocytes in the presence of conditioned medium derived from LFW273-treated Snailfl/fl ECs.
LFW273 (25-50 mg/kg, orally, sterile normal saline (0.9% NaCl solution)) attenuates atherosclerosis progression in a canonical mouse model, decreases necrotic core area in atherosclerotic plaques, dislays potent anti-atherosclerotic effects in mice.