Highly Specific L-Type Amino Acid Transporter 1 Inhibition by JPH203 as a Potential Pan-Cancer Treatment

Abstract

Accelerated cancer cell growth requires a massive intake of amino acids. Overexpression of L-type (large) amino acid transporter 1 (LAT1) on the cancer cell membrane facilitates such a demand, which is limited in normal organs. Therefore, LAT1 overexpression is ideal as a molecular cancer therapeutic target. JPH203, a LAT1-selective non-transportable blocker, had demonstrated LAT1 inhibition in <10 µM IC50 values and effectively suppressed cancer cell growth in studies involving several types of cancer cell lines and tumor xenograft models. A limited phase I clinical trial was performed on five different solid tumors and showed that JPH203 is well-tolerated and has a promising activity for the treatment of bile duct cancer. This review details the development and prospect of JPH203 as a LAT1-targeting cancer therapy.

The Molecular Interaction and Admet Prediction of Modified Jph203 as a Potential Radiopharmaceutical Kit for Molecular Imaging of Cancer: An in Silico Research

“…BCH and 4F2Hc that were contained in the selected microscopy structure of LAT-1 must be extracted from the LAT-1 structure and re-docked to verify that the molecular docking software can reproduce the agonist conformation of the native ligand (N3). The result is valid if the obtained Root Mean Square Deviation (RMSD) value is ≤2.0 Å [7]. The best-docked N3 conformation showed an RMSD of 1.827 Å compared to the previous pose (table 1).…”

“…LAT-1 can distribute eight of the nine essential amino acids to certain body areas such as the placenta and blood-brain barrier so that LAT-1 is said to be one of the main proteins in cell growth and development [6]. In addition, LAT-1 has overexpression and is highly selective against cancer cells, but its distribution is limited to normal cells [7]. The overexpression of LAT-1 in cancer cells and its ability to deliver substrates makes LAT-1 become a promising target for therapy and diagnostic (theranostic) molecules (fig.…”

Transcriptomic data analysis of melanocytes and melanoma cell lines of LAT transporter genes for precise medicine

“…There are several dozen types of amino acids transporters, and one of the most important is the SLC family which includes SLC7A5 (LAT1), SLC7A8 (LAT2), SLC43A1 (LAT3), and SLC43A2 (LAT4). The abbreviation LATs means that their transport large neutral amino acids [2,3].…”

Molecular Docking and Admet Prediction of 5-Benzyloxytryptophan as a Potential Radiopharmaceutical Kit for Molecular Imaging of Cancer

“…The large-type amino acid transporter (LAT-1) is an antiporter of ubiquitous Na+and H+involved in the uptake of essential amino acids of the cells. LAT-1 is over-expressed in human cancer cells due to its increased demand for amino acids, but its distribution is limited to normal cells [1][2][3][4]. LAT-1 can distribute eight of the nine essential amino acids at somebody areas, such as the blood-brain barrier and placenta [5].…”