ReviewDrug metabolism and disposition: the biological fate of chemicals2014
The major facilitative folate transporters solute carrier 19A1 and solute carrier 46A1: biology and role in antifolate chemotherapy of cancer.
Review in Drug metabolism and disposition: the biological fate of chemicals, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 55 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
55 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.
- Reduced folate carrier 1 G80A polymorphism is correlated with elevated methotrexate-induced toxicity in pediatric acute lymphoblastic leukemia patients: a systemic meta-analysis.World journal of surgical oncology · 2026Pooled it
- The SLC-ome of membrane transport: from molecular discovery to physiology and clinical applications.Physiological reviews · 2026Review
- Functional genomics and proteomics identify Folate Carrier SLC19A1 as a predictor of pralatrexate sensitivity in diverse T-cell lymphoma models.Molecular cancer therapeutics · 2026Article
- Serine Hydroxymethyltransferase (SHMT) in biology and disease: molecular mechanisms and therapeutic targeting.Journal of translational medicine · 2026Review
- Determination of the pyrrolo[2,3-d] pyrimidine antifolate AGF94 from a preclinical murine study using a simple UHPLC-MS/MS assay.Journal of chromatography. B, Analytical technologies in the biomedical and life sciences · 2025Article
- Integrating functional genomics and proteomics identifies Folate Carrier SLC19A1 as a predictor of pralatrexate sensitivity in T-cell lymphoma.bioRxiv : the preprint server for biology · 2025Article
- Transporters in vitamin uptake and cellular metabolism: impacts on health and disease.Life metabolism · 2025Review
- Advancements and limitations in traditional anti-cancer therapies: a comprehensive review of surgery, chemotherapy, radiation therapy, and hormonal therapy.Discover oncology · 2025Review
- Identification of locally advanced rectal cancer-related genes based on transcriptome and mendelian randomization analysis with biological validation.Frontiers in immunology · 2025Article
- Role of Mitochondrial and Cytosolic Folylpolyglutamate Synthetase in One-Carbon Metabolism and Antitumor Efficacy of Mitochondrial-Targeted Antifolates.Molecular pharmacology · 2024Article
- Structural Characterization of 5-Substituted Pyrrolo[3,2-Biochemistry · 2024Article
- Discovery of Tumor-Targeted 6-Methyl Substituted Pemetrexed and Related Antifolates with Selective Loss of RFC Transport.ACS medicinal chemistry letters · 2023Article
- Structure-Based Design of Transport-Specific Multitargeted One-Carbon Metabolism Inhibitors in Cytosol and Mitochondria.Journal of medicinal chemistry · 2023Article
- How Cryo-EM Has Expanded Our Understanding of Membrane Transporters.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- The evolution of folate supplementation - from one size for all to personalized, precision, poly-paths.Journal of translational internal medicine · 2023Article
- Multitargeted 6-Substituted Thieno[2,3-ACS pharmacology & translational science · 2023Article
- First-in-class multifunctional TYMS nonclassical antifolate inhibitor with potent in vivo activity that prolongs survival.JCI insight · 2023Article
- Immunodeficiency associated with a novel functionally defective variant of SLC19A1 benefits from folinic acid treatment.Genes and immunity · 2023Article
- Molecular mechanism of substrate recognition by folate transporter SLC19A1.Cell discovery · 2022Article
- Biology and therapeutic applications of the proton-coupled folate transporter.Expert opinion on drug metabolism & toxicology · 2022Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
This review summarizes the biology of the major facilitative membrane transporters, the reduced folate carrier (RFC) (Solute Carrier 19A1) and the proton-coupled folate transporter (PCFT) (Solute Carrier 46A1). Folates are essential vitamins, and folate deficiency contributes to a variety of health disorders. RFC is ubiquitously expressed and is the major folate transporter in mammalian cells and tissues. PCFT mediates the intestinal absorption of dietary folates and appears to be important for transport of folates into the central nervous system. Clinically relevant antifolates for cancer, such as methotrexate and pralatrexate, are transported by RFC, and loss of RFC transport is an important mechanism of methotrexate resistance in cancer cell lines and in patients. PCFT is expressed in human tumors, and is active at pH conditions associated with the tumor microenvironment. Pemetrexed is an excellent substrate for both RFC and PCFT. Novel tumor-targeted antifolates related to pemetrexed with selective membrane transport by PCFT over RFC are being developed. In recent years, there have been major advances in understanding the structural and functional properties and the regulation of RFC and PCFT. The molecular bases for methotrexate resistance associated with loss of RFC transport and for hereditary folate malabsorption, attributable to mutant PCFT, were determined. Future studies should continue to translate molecular insights from basic studies of RFC and PCFT biology into new therapeutic strategies for cancer and other diseases.
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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.