M-phase inducer phosphatase A and C (Cdc25A/C)

Cdc25A and Cdc25C are dual-specificity phosphatases that act as key regulators of the eukaryotic cell cycle by activating cyclin-dependent kinases (CDKs) [1]. They function by removing inhibitory phosphate groups from specific threonine and tyrosine residues (Thr14 and Tyr15) on CDKs, which is a prerequisite for the progression of the cell cycle through the G1/S and G2/M checkpoints [2]. Cdc25A is primarily involved in the G1/S transition and the initiation of DNA replication, while Cdc25C is essential for the entry into mitosis via the activation of the CDK1/Cyclin B complex [3]. These enzymes are frequently overexpressed in a wide variety of human cancers, including breast, lung, and colorectal carcinomas, where their high levels are often associated with poor clinical outcomes and increased tumor aggressiveness [4]. Consequently, Cdc25A and Cdc25C have emerged as attractive targets for anticancer drug development, leading to the identification of various inhibitors such as quinones, sulfonamides, and phosphate bioisosteres [5]. However, the clinical advancement of these inhibitors has been hampered by challenges related to metabolic instability, poor bioavailability, and the non-specific toxicity associated with the redox-active nature of many early compounds [6]. References: [1] UniProt (P30304, P30307); [2] Boutros, R., et al. (2007) Nat Rev Cancer; [3] Kristjansdottir, K., & Rudolph, J. (2004) Chem Biol; [4] Lavecchia, A., et al. (2010) Mini Rev Med Chem; [5] Brezak, M. C., et al. (2004) Cancer Res; [6] Kar, S., et al. (2006) Curr Cancer Drug Targets.

Other names

Cell division cycle 25 homolog ACell division cycle 25 homolog CDual specificity phosphatase Cdc25ADual specificity phosphatase Cdc25CM-phase inducer phosphatase 1M-phase inducer phosphatase 3Cdc25ACdc25C

Small molecule inhibition of the phosphatase catalytic domain, preventing the removal of inhibitory phosphate groups from Cyclin-Dependent Kinases (CDKs), which leads to cell cycle arrest at G1/S or G2/M phases [3, 4].