ArticleJournal of cellular and molecular medicine2022
Pharmacologic inhibition of LAT1 predominantly suppresses transport of large neutral amino acids and downregulates global translation in cancer cells.
Article in Journal of cellular and molecular medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The trial behind it
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Who cites it
25 citing papers in PubMed, 31 citations in OpenAlex.
- Long-lasting Inhibition of L-type Amino Acid Transporter 1 by Nanvuranlat is Associated with Prolonged Cellular Retention Counteracted by Cancer-type OATP1B3 in Cholangiocarcinoma Cells.Pharmaceutical research · 2026Article
- Phenylalanine exacerbates psoriasiform inflammation through NF‑κB‑mediated dendritic cell activation and Th17 polarization.International journal of molecular medicine · 2026Article
- Anti-Tumor Potential of Selective L-Type Amino Acid Transporter (LAT1) Inhibitor, JPH203, in Patient-Derived Canine Bladder Cancer Organoids.International journal of molecular sciences · 2026Article
- Article
- Phenylalanine homeostasis in metabolic disorders: epidemiological trends, pathophysiological mechanisms, and clinical treatment.Frontiers in endocrinology · 2026Review
- Sustained reductions in valine and isoleucine mediate anti-cancer pharmacological effects of inhibiting amino acid transporter LAT1 in cancer cells.Cancer & metabolism · 2025Article
- Treatment with L-type amino acid transporter 1 inhibitor JPH203 enhances protein synthesis in C2C12 myotubes.Scientific reports · 2025Article
- Astatine-211-Labeled Therapy Targeting Amino Acid Transporters: Overcoming Drug Resistance in Non-Small Cell Lung Cancer.International journal of molecular sciences · 2025Review
- Pharmacological and structural insights into nanvuranlat, a selective LAT1 (SLC7A5) inhibitor, and its N-acetyl metabolite with implications for cancer therapy.Scientific reports · 2025Article
- Branched-Chain Amino Acid Metabolic Reprogramming and Cancer: Molecular Mechanisms, Immune Regulation, and Precision Targeting.Oncology research · 2025Review
- Synthesis, Cytotoxicity, and Mechanistic Evaluation of Tetrahydrocurcumin-Amino Acid Conjugates as LAT1-Targeting Anticancer Agents in C6 Glioma Cells.International journal of molecular sciences · 2024Article
- The Biology and Biochemistry of Kynurenic Acid, a Potential Nutraceutical with Multiple Biological Effects.International journal of molecular sciences · 2024Review
- Regulation of placental amino acid transport in health and disease.Acta physiologica (Oxford, England) · 2024Review
- Amino acid transporters within the solute carrier superfamily: Underappreciated proteins and novel opportunities for cancer therapy.Molecular metabolism · 2024Review
- Exploring Amino Acid Transporters as Therapeutic Targets for Cancer: An Examination of Inhibitor Structures, Selectivity Issues, and Discovery Approaches.Pharmaceutics · 2024Review
- Current Standards, Multidisciplinary Approaches, and Future Directions in the Management of Extrahepatic Cholangiocarcinoma.Current treatment options in oncology · 2024Review
- OCTN1 mediates acetylcholine transport in the A549 lung cancer cells: possible pathophysiological implications.Frontiers in molecular biosciences · 2024Article
- The human LAT1-4F2hc (SLC7A5-SLC3A2) transporter complex: Physiological and pathophysiological implications.Basic & clinical pharmacology & toxicology · 2023Review
- Inhibition of cancer-type amino acid transporter LAT1 suppresses B16-F10 melanoma metastasis in mouse models.Scientific reports · 2023Article
- Small molecule inhibitors for cancer metabolism: promising prospects to be explored.Journal of cancer research and clinical oncology · 2023Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
L-type amino acid transporter 1 (LAT1; SLC7A5), which preferentially transports large neutral amino acids, is highly upregulated in various cancers. LAT1 supplies cancer cells with amino acids as substrates for enhanced biosynthetic and bioenergetic reactions and stimulates signalling networks involved in the regulation of survival, growth and proliferation. LAT1 inhibitors show anti-cancer effects and a representative compound, JPH203, is under clinical evaluation. However, pharmacological impacts of LAT1 inhibition on the cellular amino acid transport and the translational activity in cancer cells that are conceptually pivotal for its anti-proliferative effect have not been elucidated yet. Here, we demonstrated that JPH203 drastically inhibits the transport of all the large neutral amino acids in pancreatic ductal adenocarcinoma cells. The inhibitory effects of JPH203 were observed even in competition with high concentrations of amino acids in a cell culture medium. The analyses of the nutrient-sensing mTORC1 and GAAC pathways and the protein synthesis activity revealed that JPH203 downregulates the global translation. This study demonstrates a predominant contribution of LAT1 to the transport of large neutral amino acids in cancer cells and the suppression of protein synthesis by JPH203 supposed to underly its broad anti-proliferative effects across various types of cancer cells.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.