Concentrative nucleoside transporter 1 (CNT1) (CNT1)

Concentrative nucleoside transporter 1 (CNT1), encoded by the SLC28A1 gene, is a sodium-dependent symporter primarily responsible for the active uptake of pyrimidine nucleosides and adenosine across the plasma membrane [1, 3, 7]. It is predominantly expressed in the apical membranes of epithelial cells in the kidney, small intestine, and liver, where it facilitates the absorption and reabsorption of physiological nucleosides [7, 11]. Beyond its physiological role, CNT1 is a critical determinant of the pharmacokinetics and cellular entry of various nucleoside-derived drugs used in oncology and virology [7, 13]. Key substrates include anticancer agents like gemcitabine and cytarabine, as well as antiviral drugs such as zidovudine and stavudine [11, 13, 15]. In many malignancies, including pancreatic and colorectal cancers, CNT1 expression is significantly downregulated, which serves as a primary mechanism for resistance to nucleoside-based chemotherapies [4, 14, 15]. Conversely, high expression of the transporter in tumor tissues is often associated with improved clinical response to these treatments [7, 8]. Recent research also suggests that CNT1 may function as a transceptor, influencing cell signaling pathways related to the cell cycle and migration independently of its transport function [12]. Genetic polymorphisms in the SLC28A1 gene, such as the D521N variant, have been linked to altered drug disposition and increased risk of treatment-related toxicities [7].

Other names

SLC28A1Solute carrier family 28 member 1Sodium/nucleoside cotransporter 1Na(+)/nucleoside cotransporter 1hCNT1cit

CNT1 acts as a substrate-specific transporter that facilitates the active, sodium-dependent influx of nucleoside analogs into target cells, thereby increasing their intracellular concentration and subsequent pharmacological activity [7, 8, 11, 13].