A phosphorylated prodrug for the inhibition of Pin1

Fmoc-pSer-Ψ[(Z)CHC]-Pro-(2)-N-(3)-ethylaminoindole 1 showed moderate inhibition towards the mitotic regulator, Pin1 (IC50 = 28.3 μM). To improve the cell permeability, the charged phosphate was masked as the bis-pivaloyloxymethyl (POM) phosphate in Fmoc-(bisPOM)-pSer-Ψ[(Z)CHC]-Pro-(2)-N-(3)-ethylaminoindole 2. Antiproliferative activity towards A2780 ovarian cancer cells of 1 (IC50 = 46.2 μM) was improved significantly in 2 (IC50 = 26.9 μM), comparable to the IC50 of 1 towards Pin1 enzymatic activity.