Solute carrier family 19 member 1 (Reduced folate carrier 1) (SLC19A1)

Solute carrier family 19 member 1, commonly known as Reduced Folate Carrier 1 (RFC-1), is a transmembrane protein that serves as the primary mechanism for the uptake of reduced folates and antifolate drugs into mammalian cells (UniProt P41440). It functions as a bidirectional, electroneutral anion exchanger, transporting folates into the cytoplasm in exchange for organic phosphates (PubMed: 10551317). In clinical oncology, RFC-1 is the critical entry point for pralatrexate, an antifolate specifically engineered to have a significantly higher affinity for this transporter compared to methotrexate (PubMed: 21245485). This enhanced affinity facilitates greater intracellular accumulation of the drug, particularly in tumor cells that overexpress RFC-1, such as those in peripheral T-cell lymphoma (StatPearls: NBK545259). Once internalized, pralatrexate is polyglutamylated and inhibits dihydrofolate reductase, disrupting DNA synthesis and leading to apoptosis. The efficacy of pralatrexate is thus highly dependent on the functional expression of RFC-1, and alterations in this transporter are a known mechanism of drug resistance (PubMed: 19724001).

Other names

RFC1Reduced folate carrier 1Folate transporter 1FOLTIFC1SLC19A1RFC-1

Pralatrexate acts as a high-affinity substrate for the RFC-1 transporter, which facilitates its internalization into the cell; once inside, the drug is polyglutamylated by folylpolyglutamate synthetase (FPGS), leading to the potent inhibition of dihydrofolate reductase (DHFR) and other folate-dependent enzymes (FDA Label: Folotyn).