(4-Chloro-3-nitrophenyl)(4-(2-fluorophenyl)piperazin-1-yl)Methanone

Uses

SMI-481 is a yeast phosphatidylinositol transfer proteins (PITP) Sec14 inhibitor.

Biological Activity

SMI481 is a selective small-molecule inhibitor (SMI) of the yeast phosphatidylinositol transfer protein (PITP) Sec14, a key regulator of phosphoinositide signaling, regulating membrane trafficking through the trans-Golgi network and endosomal systems. SMI481 has an IC50 value of 211 ± 19 nM in vitro against S. cerevisiae Sec14 (WT) in a phosphatidylinositol (PtdIns) transfer assay measuring exchange of PtdIns and phosphatidylcholine between membranes and inhibited Sec14-dependent growth of WT yeast with an IC50 of 2.87 ± 0.55 μM. SMI481μs activity is believed to involve binding in the Sec14 hydrophobic cavity, a new target for studying phosphoinositide signaling with more selectivity than th at afforded by lipid kinase–directed strategies.