JPH203
LAT1 inhibitor / Selective L-type amino acid transporter 1 inhibitor (LAT1 or SLC7A5; IC50 = 140 nM for 14C-leucine uptake in S2-hLAT1 cells, and 60 nM for HT29 human colon adenocarcinoma cells: growth inhibition IC50’s = 16.4 µM and 4.1 µM respectively for S2 and HT29 cells).1 Also active in HT-29 mouse xenograft models. JPH203 is active in a variety of cancer models and has progressed to clinical trials.2 It sensitized A549 and MIA Paca-2 cells to radiation by enhancing cellular senescence via mTOR downregulation3 and sensitized EGFR-expressing cancer cell lines to gefitinib therapy4. JPH203 treatment of non-small cell lung cancer cells led to downregulation of PD-L1 suggesting that LAT1 inhibition may help overcome the immune suppressive tumor microenvironment.5
Biochemicals & reagents
1597402-27-1
KYT-0353; Nanvuralant
1) Oda et al. (2010) L-type amino acid transporter 1 inhibitors inhibit tumor cell growth; Cancer Sci. 101 173 2) Kanai (2022) Amino acid transporter LAT1 (SLC7A5) as a molecular target for cancer diagnosis and therapeutics; Pharmacol. Ther. 230 107964 3) Bo et al. (2021) LAT1 inhibitor JPH203 sensitizes cancer cells to radiation by enhancing radiation-induced cellular senescence; Transl. Oncol. 14 101212 4) Saito et al. (2018), Amino acid starvation culture condition sensitizes EGFR-expressing cancer cell lines to gefitinib-mediated cytotoxicity by inducing atypical necroptosis; Int. J. Oncol. 52 1165 5) Liu et al. (2021), L-Type Amino Acid Transporter 1 Regulates Cancer Stemness and the Expression of Programmed Cell Death 1 Ligand 1 in Lung Cancer Cells; Int. J. Mol. Sci. 22 10955
-20°C
PATHWAY: Amino acid metabolism; Proliferation; mTOR; Senescence -- RESEARCH AREA: Cell death -- DISEASE AREA: Cancer