NSC 663284

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 PTP1B.1Arrests cells at G1 and G2/M and inhibits cdk1 and 2 activation.2 Inhibits the growth of a variety of human tumor cell lines.3 NSC663284 acts via irreversible oxidation of the catalytic cysteine of CDC25.4

CDC25 Phosphatase Inhibitor II, NSC 663284 is a competitive CDC25 inhibitor and cell cycle arresting compound.

ChEBI: 6-chloro-7-[2-(4-morpholinyl)ethylamino]quinoline-5,8-dione is a quinolone.

A cell-permable, potent, irreversible, and competitive inhibitor of the Cdc25 phosphatase family (K_i = 29 nM, 95 nM, and 89 nM for Cdc25A, Cdc25B2, and Cdc25C, respectively) with anti-proliferative properties. Displays nearly 20- and 450-fold greater selectivity over VHR and PTP1B (IC₅₀ = 4.0 μM and >100 μM, respectively). Reported to arrest cell cycle progression, inhibit Cdk dephosphorylation, and delay tumor growth (mean IC₅₀ = 1.5 μM in NCI-60 tumor cell panel). Also shown to block ERK dephosphorylation caused by ectopic Cdc25A expression.

Potent, selective inhibitor of Cdc25 dual specificity phosphatases (K i values are 29, 95 and 89 nM for human Cdc25A, Cdc25B 2 and Cdc25C respectively); > 20- and > 450-fold selective over VHR and PTP1B phosphatases respectively. Arrests cells at both G 1 and G 2 /M phase and blocks cdk2 and cdk1 activation. Blocks proliferation of a range of human tumor cell lines (IC 50 = 0.2-35 μ M).

Cell permeable: yes

Store at +4°C

[1] JOHN S. LAZO. Discovery and Biological Evaluation of a New Family of Potent Inhibitors of the Dual Specificity Protein Phosphatase Cdc25[J]. Journal of Medicinal Chemistry, 2001, 44 24: 4042-4049. DOI:10.1021/jm0102046
[2] LIXIA PU. Dual G1 and G2 phase inhibition by a novel, selective Cdc25 inhibitor 6-chloro-7-[corrected](2-morpholin-4-ylethylamino)-quinoline-5,8-dione.[J]. The Journal of Biological Chemistry, 2002, 277 49: 46877-46885. DOI:10.1074/jbc.m207902200
[3] YUSHENG HAN. NAD(P)H:quinone oxidoreductase-1-dependent and -independent cytotoxicity of potent quinone Cdc25 phosphatase inhibitors.[J]. Journal of Pharmacology and Experimental Therapeutics, 2004, 309 1: 64-70. DOI:10.1124/jpet.103.059477
[4] MARNI BRISSON. Redox regulation of Cdc25B by cell-active quinolinediones.[J]. Molecular Pharmacology, 2005, 68 6: 1810-1820. DOI:10.1124/mol.105.016360