02000nas a2200253   4500000000100000008004100001260001600042653001200058653001100070653001600081653001400097100001400111700001300125700001600138700002000154700001300174700001600187700001500203700001900218700001700237245013200254520134600386022001401732       2013                            d  c2013 Dec 1610aleprosy10aCancer10aClofazimine10aTreatment1 aKoval A V1 aVlasov P1 aShichkova P1 aKhunderyakova S1 aMarkov Y1 aPanchenko J1 aVolodina A1 aKondrashov F A1 aKatanaev V L00aAnti-leprosy drug Clofazimine inhibits growth of triple-negative breast cancer cells via inhibition of canonical Wnt signaling.3 aResearch on existing drugs often discovers novel mechanisms of their action and leads to the expansion of their therapeutic scope and subsequent remarketing. The Wnt signaling pathway is of the immediate therapeutic relevance, as it plays critical roles in cancer development and progression. However, drugs which disrupt this pathway are unavailable despite the high demand. Here we report an attempt to identify antagonists of the Wnt-FZD interaction among the library of the FDA-approved drugs. We performed an in silico screening which brought up several potential antagonists of the ligand-receptor interaction. 14 of these substances were tested using the TopFlash luciferase reporter assay and 4 of them identified as active and specific inhibitors of the Wnt3a-induced signaling. However, further analysis through GTP-binding and β-catenin stabilization assays showed that the compounds do not target the Wnt-FZD pair, but inhibit the signaling at downstream levels. We further describe the previously unknown inhibitory activity of an anti-leprosy drug clofazimine in the Wnt pathway and provide data demonstrating its efficiency in suppressing growth of Wnt-dependent triple-negative breast cancer cells. These data provide a basis for further investigations of the efficiency of clofazimine in treatment of Wnt-dependent cancers.  a1873-2968