383907-43-5 Usage
Description
NSC 663284 is a potent, selective, and irreversible inhibitor of CDC25 phosphatases, with Ki values of 29, 95, and 89 nM for human CDC25A, B2, and C, respectively. It is highly selective over VHR and PTP1B, and it arrests cells at G1 and G2/M phases, inhibiting cdk1 and 2 activation. NSC 663284 inhibits the growth of various human tumor cell lines and acts via irreversible oxidation of the catalytic cysteine of CDC25.
Uses
Used in Pharmaceutical Industry:
NSC 663284 is used as a CDC25 phosphatase inhibitor and cell cycle arresting compound for its potential in cancer treatment. Its ability to inhibit the growth of various human tumor cell lines makes it a promising candidate for further research and development in oncology.
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
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
Check Digit Verification of cas no
The CAS Registry Mumber 383907-43-5 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 3,8,3,9,0 and 7 respectively; the second part has 2 digits, 4 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 383907-43:
(8*3)+(7*8)+(6*3)+(5*9)+(4*0)+(3*7)+(2*4)+(1*3)=175
175 % 10 = 5
So 383907-43-5 is a valid CAS Registry Number.
InChI:InChI=1/C15H16ClN3O3/c16-11-13(18-4-5-19-6-8-22-9-7-19)15(21)12-10(14(11)20)2-1-3-17-12/h1-3,18H,4-9H2
383907-43-5Relevant articles and documents
Discovery and biological evaluation of a new family of potent inhibitors of the dual specificity protein phosphatase Cdc25
Lazo,Aslan,Southwick,Cooley,Ducruet,Joo,Vogt,Wipf
, p. 4042 - 4049 (2001)
The Cdc25 dual specificity phosphatases have central roles in coordinating cellular signaling processes and cell proliferation, but potent and selective inhibitors are lacking. We experimentally examined the 1990 compound National Cancer Institute Diversity Set and then computationally selected from their 140 000 compound repository 30 quinolinediones of which 8 had in vitro mean inhibitory concentrations 2 as compared with VHR or PTP1B phosphatases, respectively. NSC 663284 exhibited mixed competitive kinetics against Cdc25A, Cdc25B2, and Cdc25C with Ki values of 29, 95, and 89 nM, respectively. As compared with NSC 663284, the regioisomer 7-chloro-6-(2-morpholin-4-ylethylamino)quinoline-5,8-dione was 3-fold less active against Cdc25B2 in vitro and less potent as a growth inhibitor of human breast cancer cells. Computational electrostatic potential mapping suggested the need for an electron-deficient 7-position for maximal inhibitor activity. Using a chemical complementation assay, we found that NSC 663284 blocked cellular Erk dephosphorylation caused by ectopic Cdc25A expression.
