Human equilibrative nucleoside transporter 1 and human concentrative nucleoside transporter 3 (hENT1 and hCNT3)

Human equilibrative nucleoside transporter 1 (hENT1) and human concentrative nucleoside transporter 3 (hCNT3) are integral membrane proteins that mediate the uptake of physiological nucleosides and synthetic nucleoside analogs (PMID: 24583590). hENT1, a member of the SLC29 family, functions through facilitated diffusion and is the most widely expressed nucleoside transporter in human tissues (UniProt: Q99808). hCNT3, belonging to the SLC28 family, is a specialized concentrative transporter that utilizes sodium or proton gradients to drive substrate entry against concentration gradients (UniProt: Q9Y2E5). These transporters are pharmacologically significant because they serve as the primary gateways for several essential chemotherapeutic agents, including gemcitabine, cytarabine, and fludarabine (PMID: 15150565). In clinical oncology, the expression levels of hENT1 and hCNT3 are often used as predictive biomarkers; for instance, high hENT1 expression is associated with improved survival in pancreatic cancer patients treated with gemcitabine (PMID: 23690420). Beyond drug delivery, they play a vital role in regulating extracellular adenosine concentrations, which modulates various physiological processes such as vascular tone and neurotransmission.

Other names

SLC29A1SLC28A3Equilibrative nucleoside transporter 1Concentrative nucleoside transporter 3Solute carrier family 29 member 1Solute carrier family 28 member 3ENT1CNT3

These transporters facilitate the cellular influx of nucleoside analog prodrugs, which is a prerequisite for their intracellular phosphorylation into active cytotoxic metabolites. hENT1 operates via facilitated diffusion (equilibrative), while hCNT3 utilizes sodium or proton gradients to actively concentrate substrates within the cell (PMID: 15150565, 24583590).