JPH203 dihydrochloride (KYT-0353 dihydrochloride) is a tyrosine analog, acts as a selective inhibitor of L-type amino acid transporter 1 (LAT1), and is used in cancer research.

JPH203 (30 mM) induces mitochondria-dependent apoptosis in Saos2 human osteosarcoma cells. JPH203 (0.001-100 μM) inhibits 14C-leucine (1.0 μM) uptake slightly in FOB cells with an IC50 value of 92.12 ± 10.71 μM, but potently exihibts such effects in Saos2 cells with an IC50 value of 1.31 ± 0.27 μM. JPH203 (0.01 to 30 mM, 1-4 d) potently inhibits cell proliferation in Saos2 cells in a dose- and time-dependent manner, with an IC50 of 4.09-0.09 mM, but slightly inhibits that of FOB cells, with an IC50 of 24.1-2.8 mM.JPH203 Dihydrochloride is a selective inhibitor of LAT1. JPH203 inhibits 14C-leucine uptake in S2-hLAT1 and HT-29 cells, with IC50s of 0.14 μM and 0.06 μM. JPH203 (3-1000 μM) exhibits concentration-dependent inhibitory effects on S2-hLAT1 cell growth with an IC50 of 16.4 μM. JPH203 also displays inhibitory activities against HT-29 cell growth, with an IC50 value of 4.1 μM. JPH203 (0.001-100 μM) inhibits the 14C-leucine (1.0 μM) uptake in a concentration dependent way by the YD-38 cells with an IC50 value of 0.79 ± 0.06 μM. JPH203 slightly shows such effects in normal human oral keratinocytes (NHOKs). JPH203 (0.01-30 mM, 1-4 d) completely inhibits the proliferation of YD-38 cells in a dose- and time-dependent manner. However, JPH203 slightly inhibits the proliferation of NHOKs. JPH203 (30 mM) induces apoptosis of YD-38 cells. JPH203 (3 mM) also increases the level of cleaved PARP in activation of the caspases cascade.

JPH203 exhibits dose-dependent inhibition on HT-29 tumor growth in nude mice.