ArticleInternational journal of molecular sciences2023
Insights into the Transport Cycle of LAT1 and Interaction with the Inhibitor JPH203.
Article in International journal of molecular sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 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
11 citing papers in PubMed, 20 citations in OpenAlex.
- Phenylalanine Transport through LAT1: Insights from Molecular Dynamics, Steered Molecular Dynamics, and Targeted Molecular Dynamics.The journal of physical chemistry. B · 2026Article
- Microbiome driven modulation of neurotransmitters: implications for neurotransmission and mood disorders.Frontiers in microbiology · 2026Review
- L‑type amino acid transporter 1 in enhancing boron neutron capture therapy: Mechanisms, challenges and future directions (Review).International journal of molecular medicine · 2025Review
- FastConformation: A Standalone ML-Based Toolkit for Modeling and Analyzing Protein Conformational Ensembles at Scale.bioRxiv : the preprint server for biology · 2025Article
- The Multifaceted Role of L-Type Amino Acid Transporter 1 at the Blood-Brain Barrier: Structural Implications and Therapeutic Potential.Molecular neurobiology · 2025Review
- The Development of LAT1 Efflux Agonists as Mechanistic Probes of Cellular Amino Acid Stress.Biomolecules · 2024Article
- OCTN1 mediates acetylcholine transport in the A549 lung cancer cells: possible pathophysiological implications.Frontiers in molecular biosciences · 2024Article
- Article
- LAT1 (SLC7A5) catalyzes copper(histidinate) transport switching from antiport to uniport mechanism.iScience · 2023Article
- Genetic Ablation of LAT1 Inhibits Growth of Liver Cancer Cells and Downregulates mTORC1 Signaling.International journal of molecular sciences · 2023Article
- Editorial for Special Issue-"Early-Stage Drug Discovery: Advances and Challenges".International journal of molecular sciences · 2023Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The large Amino Acid Transporter 1 (LAT1) is an interesting target in drug discovery since this transporter is overexpressed in several human cancers. Furthermore, due to its location in the blood-brain barrier (BBB), LAT1 is interesting for delivering pro-drugs to the brain. In this work, we focused on defining the transport cycle of LAT1 using an in silico approach. So far, studies of the interaction of LAT1 with substrates and inhibitors have not considered that the transporter must undergo at least four different conformations to complete the transport cycle. We built outward-open and inward-occluded conformations of LAT1 using an optimized homology modelling procedure. We used these 3D models and the cryo-EM structures in outward-occluded and inward-open conformations to define the substrate/protein interaction during the transport cycle. We found that the binding scores for the substrate depend on the conformation, with the occluded states as the crucial steps affecting the substrate affinity. Finally, we analyzed the interaction of JPH203, a high-affinity inhibitor of LAT1. The results indicate that conformational states must be considered for in silico analyses and early-stage drug discovery. The two built models, together with the available cryo-EM 3D structures, provide important information on the LAT1 transport cycle, which could be used to speed up the identification of potential inhibitors through in silico screening.
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.