Deoxycytidine kinase (dCK) (dCK)

Deoxycytidine kinase (dCK) is a rate-limiting enzyme in the deoxyribonucleoside salvage pathway, responsible for phosphorylating deoxycytidine, deoxyadenosine, and deoxyguanosine into their respective monophosphates (UniProt P27707) [1]. While its primary physiological role is maintaining nucleotide pools for DNA synthesis and repair, it is clinically significant as the primary activating enzyme for a wide array of nucleoside analog chemotherapeutics (NCBI Gene 1633) [2]. Drugs such as gemcitabine and cytarabine are administered as prodrugs that require dCK-mediated phosphorylation to eventually form active triphosphates, which inhibit DNA polymerases or incorporate into DNA to cause chain termination and apoptosis (DrugBank DB00441, DB00987) [4]. Consequently, dCK activity is a critical determinant of the efficacy of these agents in treating various hematological malignancies and solid tumors (PMID: 25103573) [3]. Low levels of dCK expression or activity are frequently associated with acquired drug resistance, making it a focal point for biomarker development and therapeutic monitoring (PMID: 25103573) [3].

Other names

DCKDeoxycytidine kinaseNucleoside kinase

Activation of nucleoside analog prodrugs through phosphorylation to monophosphates, which are then further phosphorylated to active triphosphates that inhibit DNA polymerases and incorporate into DNA strands to cause chain termination (DrugBank DB00441) [4].