Solute carrier family 28 member 3 (SLC28A3) (SLC28A3)

Solute carrier family 28 member 3 (SLC28A3), also known as Concentrative nucleoside transporter 3 (CNT3), is a transmembrane protein that mediates the uptake of natural nucleosides and synthetic nucleoside analogs into cells [1, 5]. Unlike other members of the SLC28 family, SLC28A3 has a broad substrate specificity, transporting both purine and pyrimidine nucleosides, and can utilize both sodium and proton gradients as driving forces [1, 3]. It is widely expressed in tissues such as the pancreas, intestine, and bone marrow, and plays a pivotal role in the pharmacokinetics of various anticancer and antiviral drugs [1, 2]. In oncology, SLC28A3 is a key determinant of the cellular entry and efficacy of drugs like gemcitabine, fludarabine, and cladribine [2, 5, 8]. Furthermore, genetic variants of SLC28A3 have been identified as significant biomarkers for predicting drug-induced toxicities, most notably providing a protective effect against anthracycline-induced cardiotoxicity in pediatric patients [7, 10, 11]. Understanding the expression and polymorphic nature of SLC28A3 is essential for personalizing chemotherapy and managing potential drug-drug interactions [5, 15]. The transporter's ability to function in acidic environments via proton coupling makes it particularly relevant in the context of the tumor microenvironment [1, 3]. Recent structural studies using cryo-electron microscopy have elucidated its trimeric architecture and elevator-type transport mechanism, providing insights for future drug design [5].

Other names

Concentrative nucleoside transporter 3hCNT3cibCNT3Solute carrier family 28 member 3

Mediates the cellular uptake of nucleosides and nucleoside analogs via sodium-coupled or proton-coupled symport mechanisms.