Calix[4]Arene <i>α</i> ‐Ketophosphonic Acids as Photoactivatable Inhibitors of Protein Tyrosine Phosphatases

ABSTRACT Protein tyrosine phosphatases (PTPs) can be involved in the development of different human diseases, including cancer. In this study, in vitro experiments were performed to evaluate the inhibitory effect of the calix[4]arene α‐ketophosphonic acids on the activities of PTP1B, TC‐PTP, SHP2, and MEG2 under irradiation of 365 nm UV light. Among the compounds tested, calix[4]arene bis‐α‐ketophosphonic acids substituted at the lower rim by two n ‐propyl or n ‐butyl groups significantly increased the UV‐induced inhibition of the PTPs, demonstrating IC 50 values in the low‐micromolar range. The observed pseudo‐first‐order rate constants for the loss of activity of PTP1B and SHP2 depended linearly on the inhibitor concentration. The value of the second‐order rate constant for SHP2 exceeded that for PTP1B. This work demonstrates that calix[4]arene can be used as a scaffold for designing photoactivatable inhibitors targeting PTPs.