ArticleJournal of medicinal chemistry2018
Reevaluating the Substrate Specificity of the L-Type Amino Acid Transporter (LAT1).
Article in Journal of medicinal chemistry, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
54 citing papers in PubMed, 77 citations in OpenAlex.
- Discovery of 3-(N-phenylsulfamoyl)-L-phenylalanine derivatives as novel and orally available LAT1-selective inhibitors.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Article
- Article
- Phenylalanine Transport through LAT1: Insights from Molecular Dynamics, Steered Molecular Dynamics, and Targeted Molecular Dynamics.The journal of physical chemistry. B · 2026Article
- Associations of plasma metabolites with protein biomarkers linked to Alzheimer's disease pathology in the Rotterdam Study.Alzheimer's research & therapy · 2026Article
- Evaluating the Utility and Constraints of the Competitive Counter Flow (CCF) Assay in OATP1B1 Substrate Profiling.The AAPS journal · 2026Article
- l‑Boronophenylalanine (l-BPA) Dipeptide Prodrugs Enhance Boron Delivery to Tumors, Facilitate Tumor Eradication and Induce Tumor Vaccine Effect in Mice Following Neutron Irradiation.ACS pharmacology & translational science · 2026Article
- A LAT1-Compatible, Leadlike Tyrosine-Naphthoquinone Conjugate With Anticancer Activity.Drug development research · 2026Article
- From Polyphenols to Prodrugs: Bridging the Blood-Brain Barrier with Nanomedicine and Neurotherapeutics.International journal of molecular sciences · 2026Review
- Ginger and Its Purified Major Components Inhibit Clinically Relevant Uptake and Efflux Transporters In Vitro.Pharmaceutics · 2026Article
- Behavioral Alterations and Cholinergic Modulation in Zebrafish Acutely Exposed To Tyrosine.Neurotoxicity research · 2025Article
- Article
- Article
- Dynamic crosstalk between amino acid metabolism and cancer drug efficacy: From mechanisms to therapeutic opportunities.iScience · 2025Review
- The Multifaceted Role of L-Type Amino Acid Transporter 1 at the Blood-Brain Barrier: Structural Implications and Therapeutic Potential.Molecular neurobiology · 2025Review
- Radiosynthesis and Preclinical Evaluation ofMolecular pharmaceutics · 2024Article
- Exploring Amino Acid Transporters as Therapeutic Targets for Cancer: An Examination of Inhibitor Structures, Selectivity Issues, and Discovery Approaches.Pharmaceutics · 2024Review
- Improving regioselectivity of phenylalanine aminomutase fromFrontiers in bioengineering and biotechnology · 2024Article
- Membrane transporters in cell physiology, cancer metabolism and drug response.Disease models & mechanisms · 2023Review
- The human LAT1-4F2hc (SLC7A5-SLC3A2) transporter complex: Physiological and pathophysiological implications.Basic & clinical pharmacology & toxicology · 2023Review
- Targeting SLC transporters: small molecules as modulators and therapeutic opportunities.Trends in biochemical sciences · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
20 authors at 4 institutions in 2 countries.
Funding
Abstract
The L-type amino acid transporter 1 (LAT1, SLC7A5) transports essential amino acids across the blood-brain barrier (BBB) and into cancer cells. To utilize LAT1 for drug delivery, potent amino acid promoieties are desired, as prodrugs must compete with millimolar concentrations of endogenous amino acids. To better understand ligand-transporter interactions that could improve potency, we developed structural LAT1 models to guide the design of substituted analogues of phenylalanine and histidine. Furthermore, we evaluated the structure-activity relationship (SAR) for both enantiomers of naturally occurring LAT1 substrates. Analogues were tested in cis-inhibition and trans-stimulation cell assays to determine potency and uptake rate. Surprisingly, LAT1 can transport amino acid-like substrates with wide-ranging polarities including those containing ionizable substituents. Additionally, the rate of LAT1 transport was generally nonstereoselective even though enantiomers likely exhibit different binding modes. Our findings have broad implications to the development of new treatments for brain disorders and cancer.
Indexed as
Identifiers
What OpenQuestion holds
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.