NSC 663284 Property

Boiling point:

478.8±45.0 °C(Predicted)

Density 

1.41±0.1 g/cm3(Predicted)

storage temp. 

2-8°C

solubility 

DMSO: 16 mg/mL

form 

solid

pka

6.79±0.10(Predicted)

color 

red

Sensitive 

Light Sensitive

Stability:

Stable for 2 years from date of purchase as supplied. Solutions in DMSO or ethanol may be stored at -20° for up to 1 month.

Safety

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

26

WGK Germany 

3

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P405Store locked up.

NSC 663284 Chemical Properties,Usage,Production

Description

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.1?Arrests 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

Uses

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

Definition

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

General Description

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.

Biological Activity

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).

Biochem/physiol Actions

Cell permeable: yes

storage

Store at +4°C

References

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