LAPSE:2023.5551
Published Article
LAPSE:2023.5551
Highly Specific L-Type Amino Acid Transporter 1 Inhibition by JPH203 as a Potential Pan-Cancer Treatment
February 23, 2023
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.
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.
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Keywords
amino acid metabolism, cancer, JPH203, LAT1, targeted drug
Subject
Suggested Citation
Achmad A, Lestari S, Holik HA, Rahayu D, Bashari MH, Faried A, Kartamihardja AHS. Highly Specific L-Type Amino Acid Transporter 1 Inhibition by JPH203 as a Potential Pan-Cancer Treatment. (2023). LAPSE:2023.5551
Author Affiliations
Achmad A: Department of Nuclear Medicine and Molecular Theranostics, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin General Hospital, Bandung 40161, Indonesia; Oncology and Stem Cell Working Group, Faculty of Medicine, Universitas Padjadjaran, Bandung 4 [ORCID]
Lestari S: Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, Indonesia
Holik HA: Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, Indonesia [ORCID]
Rahayu D: Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, Indonesia [ORCID]
Bashari MH: Oncology and Stem Cell Working Group, Faculty of Medicine, Universitas Padjadjaran, Bandung 40161, Indonesia; Division of Pharmacology and Therapy, Department of Basic Medical Sciences, Faculty of Medicine, Universitas Padjadjaran, Bandung 40161, Indonesi
Faried A: Department of Neurosurgery, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin General Hospital, Bandung 40161, Indonesia
Kartamihardja AHS: Department of Nuclear Medicine and Molecular Theranostics, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin General Hospital, Bandung 40161, Indonesia
Lestari S: Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, Indonesia
Holik HA: Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, Indonesia [ORCID]
Rahayu D: Department of Pharmaceutical Analysis and Medicinal Chemistry, Faculty of Pharmacy, Universitas Padjadjaran, Sumedang 45363, Indonesia [ORCID]
Bashari MH: Oncology and Stem Cell Working Group, Faculty of Medicine, Universitas Padjadjaran, Bandung 40161, Indonesia; Division of Pharmacology and Therapy, Department of Basic Medical Sciences, Faculty of Medicine, Universitas Padjadjaran, Bandung 40161, Indonesi
Faried A: Department of Neurosurgery, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin General Hospital, Bandung 40161, Indonesia
Kartamihardja AHS: Department of Nuclear Medicine and Molecular Theranostics, Faculty of Medicine, Universitas Padjadjaran/Hasan Sadikin General Hospital, Bandung 40161, Indonesia
Journal Name
Processes
Volume
9
Issue
7
First Page
1170
Year
2021
Publication Date
2021-07-05
ISSN
2227-9717
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Original Submission
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PII: pr9071170, Publication Type: Review
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LAPSE:2023.5551
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https://doi.org/10.3390/pr9071170
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Feb 23, 2023
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