Potent and selective allosteric inhibitor of Wip1 phosphatase (IC50
= 6 nM). Exhibits selectivity for Wip1 over 21 other phosphatases. Increases phosphorylation of Wip1 substrates, including p53, Chk2, H2AX and ATM. Attenuates tumor cell growth in a variety of lymphoid cell lines. Also inhibits lymphoma xenograft growth in vivo
. Orally bioavailable.
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Allosteric Wip1 phosphatase inhibition through flap-subdomain interaction.
Gilmartin et al.