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.
Tantangan dalam proses penemuan dan pengembangan obat salah satunya adalah memprediksi secara klinis interaksi obat. Sehingga para ilmuan baru-baru ini banyak menggunakan Sistem Klasifikasi Disposisi Obat Biofarmasi atau dikenal dengan BDDCS untuk membantu menentukan hal tersebut. BDDCS mampu memprediksi metabolisme enzim dan efek transporter pada disposisi obat sehingga dapat menentukan ketersediaan hayati obat di dalam tubuh. BDDCS juga berguna dalam memprediksi: interaksi obat-obat; toksisitas; efek farmakogenomik dan substrat endogen; efek makanan; efek ke sistem saraf pusat; rute eliminasi obat; dan resistensi obat yang dimediasi oleh transporter. Sehingga BDDCS bisa menjadi alat prediksi yang kuat setiap kali transporter obat terlibat dalam proses fisiologis dan dapat dijadikan landasan pada tahap awal proses penemuan dan pengembangan obat. Kata Kunci : Biopharmaceutics Drug Disposition Classification System (BDDCS), efek transporter pengembangan obat, tingkat metabolisme
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