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Updated: Jul 10, 2026

Assessing Cellular Target Engagement by SHP2 (PTPN11) Phosphatase Inhibitors
Published on: July 17, 2020
A phosphorylated prodrug for the inhibition of Pin1
1Department of Chemistry, Virginia Tech, Blacksburg, VA 24061-0212, USA.
Abstract:
Fmoc-pSer-Psi[(Z)CHC]-Pro-(2)-N-(3)-ethylaminoindole 1, showed moderate inhibition towards the mitotic regulator, Pin1 (IC(50)=28.3microM). To improve the cell permeability, the charged phosphate was masked as the bis-pivaloyloxymethyl (POM) phosphate in Fmoc-(bisPOM)-pSer-Psi[(Z)CHC]-Pro-(2)-N-(3)-ethylaminoindole 2. Antiproliferative activity towards A2780 ovarian cancer cells of 1 (IC(50)=46.2microM) was improved significantly in 2 (IC(50)=26.9microM), comparable to the IC(50) of 1 towards Pin1 enzymatic activity.
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