L-type amino acid transporter (LAT) (LAT)

L-type amino acid transporters (LATs) are a family of sodium-independent nutrient transporters responsible for the cellular uptake of large neutral amino acids, such as leucine, phenylalanine, and tryptophan [1, 13]. The family consists of four members, LAT1 through LAT4, with LAT1 (SLC7A5) being the most extensively studied as a therapeutic target due to its significant overexpression in various human cancers [1, 3]. In malignant cells, LAT1 facilitates the high demand for essential amino acids required for rapid proliferation and activates the mTOR signaling pathway, which promotes protein synthesis and cell survival [16, 17]. Beyond oncology, LATs play critical roles in the blood-brain barrier, where they mediate the transport of essential nutrients and pharmacological agents like L-DOPA and gabapentin [12, 14]. Therapeutic strategies targeting LATs primarily involve the development of selective inhibitors, such as nanvuranlat (JPH203), to induce amino acid starvation in tumor cells [2, 8]. Additionally, LATs are utilized as vehicles for targeted drug delivery and as diagnostic biomarkers through amino acid-based PET imaging [6, 23].

Other names

LAT1LAT2LAT3LAT4SLC7A5SLC7A8SLC43A1SLC43A2System L transportersLarge neutral amino acid transporter

Drugs targeting L-type amino acid transporters primarily act through competitive inhibition of amino acid uptake, leading to intracellular amino acid depletion and subsequent suppression of the mTOR signaling pathway [1, 2]. Selective inhibitors like nanvuranlat (JPH203) function as non-transportable blockers that bind to the transporter's substrate-binding site, effectively starving cancer cells of essential nutrients [2, 5, 8]. Additionally, certain therapeutic agents such as melphalan and L-DOPA act as substrates, utilizing the transporter for cellular entry or crossing the blood-brain barrier [12, 21].