Three genes encode dual specificity phosphatases that are Cdc25 homologs. The phosphatases, Cdc25A through C, are proto-oncogenes and are often over-expressed in cancers. NSC 663284 is a potent, cell-permeable, and irreversible inhibitor of all Cdc25 isoforms, with preference for Cdc25A (IC50 = 29, 95, and 89 nM for Cdc25A, Cdc25B2, and Cdc25C, respectively). NSC 663284 poorly inhibits other phosphatases, including Vaccinia virus VH1-related (IC50 = 4.0 μM), PTP1B (no inhibition), and the mitogen-activated protein kinase phosphatases (MKP) MKP-1 or -3 (no inhibition). By inhibiting Cdc25 isoforms, NSC 663284 prevents the dephosphorylation and activation of Cdk1 and Cdk2, arrests cells at both G1 and G2/M phases, and prevents the proliferation of several human tumor cell lines.
