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

被引：10

作者：

Achmad, Arifudin ^{[1
,2
]}

Lestari, Shinta ^{[3
]}

Holik, Holis Abdul ^{[3
]}

Rahayu, Driyanti ^{[3
]}

Bashari, Muhammad Hasan ^{[2
,4
]}

Faried, Ahmad ^{[5
]}

Kartamihardja, Achmad Hussein Sundawa ^{[1
]}

机构：

[1] Univ Padjadjaran, Fac Med, Dept Nucl Med & Mol Theranost, Hasan Sadikin Gen Hosp, Bandung 40161, Indonesia

[2] Padjadjaran State Univ, Fac Med, Oncol & Stem Cell Working Grp, Bandung 40161, Indonesia

[3] Univ Padjadjaran, Fac Pharm, Dept Pharmaceut Anal & Med Chem, Sumedang 45363, Indonesia

[4] Univ Padjadjaran, Fac Med, Dept Basic Med Sci, Div Pharmacol & Therapy, Bandung 40161, Indonesia

[5] Padjadjaran State Univ, Fac Med, Dept Neurosurg, Hasan Sadikin Gen Hosp, Bandung 40161, Indonesia

来源：

PROCESSES | 2021年 / 9卷 / 07期

关键词：

cancer; JPH203; LAT1; targeted drug; amino acid metabolism; PROGNOSTIC-SIGNIFICANCE; CD98; EXPRESSION; LAT1; ASCT2; CHEMOTHERAPY; HALLMARKS; XCT;

D O I：

10.3390/pr9071170

中图分类号：

TQ [化学工业];

学科分类号：

0817 ;

摘要：

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 mu M 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.

引用

页数：15

共 62 条

[1] The diagnostic performance of 18F-FAMT PET and 18F-FDG PET for malignancy detection: a meta-analysis [J].