Selective inhibition of Pin1 with a covalent small molecule targeting its catalytic domain

From a mechanism-based screening we have identified a novel Pin1 suicide inhibitor, KPT-6566, able to selectively inhibit Pin1 and target it for degradation. We have performed a transcriptiomic analysis comparing Pin1 specific RNA interference in MDA-MB 231 cells with KPT-6566 treatment to assess specificity of the KPT-6566 towards Pin1. One cell line was transfected with control siRNA or Pin1 siRNA or treated with KPT-6566 or DMSO. The study comprises 10 experimental points, including duplicate experiments for each siRNA condition and triplicate experiments for the treatment with KPT-6566 or DMSO.