CDC25 phosphatases (CDC25A, B and C) play a critical role by dephosphorylating and activating cyclin-dependent kinases (CDKs) thus leading to the phosphorylation of key substrates for cell cycle progression and mitosis. Increase of expression of the members of CDC25 family have been reported in several human cancers compared to normal tissues suggesting an active role in tumorigenesis.

Here, we report the in vitro and in vivo characterization of a novel synthetic CDC25 inhibitor. This inhibitor is active against several purified human CDC25 family members (A, B2, B3, & C) in the nanomolar range. Short exposure of this compound at low concentrations are sufficient to inhibit the proliferation of a large panel of human tumor cell lines including drug resistant cell lines. Its antiproliferative activity is observed with tumor cells growing as monolayer, as well as in colony in clonogenicity assay or as spheroids in 3 dimensions. Finally, this inhibitor reduces the growth rate of human tumors xenografted in athymic mice.

Together, these results strongly support further interest in pursuing investigation of CDC25 inhibitors against human cancers.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA