Inhibitors of Cdc25 phosphatases as anticancer agents: a patent review.
BACKGROUND
The cell division cycle 25 (Cdc25) family of proteins are highly conserved dual specificity phosphatases that regulate cyclin-dependent kinases, the main gatekeepers of the eukaryotic cell division cycle. The three isoforms of Cdc25, including Cdc25A, Cdc25B and Cdc25C, appear to act on different cyclin-dependent kinase/cyclin complexes at different stages of the cell cycle. Overexpression of Cdc25A and/or Cdc25B, but not Cdc25C, has been detected in numerous cancers and is often correlated with a poor clinical prognosis. Thus, inhibition of these phosphatases may represent a promising therapeutic approach in oncology.


METHODS
The main focus of the present review is to describe the development of Cdc25 inhibitors over the years. We describe different compounds according to the decade of discovery and focus attention on molecules that were published in patents.


RESULTS
Insight into the most clinically relevant therapeutic Cdc25 analogues that have been published in over 40 patents over the past 19 years.


CONCLUSIONS
Some Cdc25 inhibitors have suppressed in vivo the growth of human tumor xenografts in animals; this confirmed the validity of using Cdc25 phosphatase inhibition as an anticancer strategy, but side effects and toxicity remain to be investigated.
Lavecchia
Antonio
A
Università di Napoli Federico II, Facoltà di Farmacia, Dipartimento di Chimica Farmaceutica e Tossicologica, Drug Discovery Laboratory, Via D. Montesano 49, Napoli, 80131, Italy. lavecchi@unina.it
Di Giovanni
Carmen
C
Novellino
Ettore
E
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology*; D015195:Drug Design; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D010330:Patents as Topic; D020033:Protein Isoforms; D023041:Xenograft Model Antitumor Assays; D020687:cdc25 Phosphatases / Q000037:antagonists & inhibitors*
D000970:Antineoplastic Agents; D020033:Protein Isoforms; D020687:cdc25 Phosphatases