NSC663284 (383907-43-5) is a potent, selective and irreversible inhibitor of CDC25 phosphatases, Ki=29, 95 and 89 nM for human CDC25A, B2 and C respectively and >20- and >450-fold selective over VHR and PTP1B1. Arrests cells at G1 and G2/M and inhibits cdk1 and 2 activation2. Inhibits the growth of a variety of human tumor cell lines3. NSC663284 acts via irreversible oxidation of the catalytic cysteine of CDC254.
1) Lazo et al. (2001), Discovery and biological evaluation of a new family of potent inhibitors of the dual specificity protein phosphatases Cdc25; J. Med. Chem., 44 4042
2) Pu et al. (2002), Dual G1 and G2 phase inhibition by a novel, selective Cdc25 inhibitor 6-chloro-7-(2-morpholin-4-ylethylamino)-quinoline-3,8-dione; J. Biol. Chem., 277 46877
3) Han et al. (2004), NAD(P)H:quinone oxidoreductase-1-dependent and independent cytotoxicity of potent quinone Cdc25 phosphatase inhibitors; J. Pharmacol. Exp. Ther., 309 64
4) Brisson et al. (2005), Redox regulation of Cdc25B by cell-active quinolonediones; Mol. Pharmacol., 68 1810