1-(2,6-Dibenzyloxybenzoyl)-3-(9H-fluoren-9-yl)-urea: A Novel Cyclophilin A Allosteric Activator

M. Lv, et al. , 425(4), 938-943, Biochem Biophys Res Commun, 2012

A small molecule compound 1-(2,6-Dibenzyloxybenzoyl)-3-(9H-fluoren-9-yl)-urea (1a) was found to be an allosteric activator of human CypA, which plays an important role in many physiological processes including protein folding, transportation, immune modulation and cell signaling. Compound 1a was screened by PPIase activity and binding affinity assay using the Octet RED system and Super Streptavidin biosensors. Its effect on ERK phosphorylation was tested in cells. The allosteric binding site and mechanism of compound 1a were also analyzed by mutagenesis in combination with molecular dynamics simulations.

Read More