A selective LAT1 inhibitor that blocks LAT1-dependent L-Leu uptake and cancer growth both in vitro and in vivo.
JPH203 (KYT-0353) selectively inhibits L-type amino acid transporter LAT1-dependent L-leucine uptake and growth in HT-29 and human LAT1-expressing S2 murine renal proximal tubule cell cultures, but not human LAT2-expressing S2 cells (IC50/GI50 = 0.06/4.1, 0.14/16.4, and >10/>1000 μM, respectively). When administered via intravenous injection (6.3-25 mg/kg/d from d0 to d13), JPH203 effectively inhibits HT-29-derived tumor growth in mice in vivo.
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Drug metabolism and pharmacokinetics, 27(1), 155-161 (2011-09-15)
Many primary human tumors and tumor cell lines highly express human L-type amino acid transporter 1 (hLAT1); cancerous cells in vivo are strongly linked to LAT1 expression. Synthetic chemistry and in vitro screening efforts have afforded a variety of novel
Most tumor cell membranes overexpress L-type amino acid transporter 1, while normal cell membranes contain l-type amino acid transporter 2; both are Na(+)-independent amino acid transporters. Therefore, compounds that selectively inhibit L-type amino acid transporter 1 offer researchers with a
Journal of pharmaceutical sciences, 102(9), 3228-3238 (2013-05-29)
JPH203 has been developed as an anticancer drug that inhibits L-type amino acid transporter 1-mediated essential amino acid uptake into tumor cells. This study sought to elucidate which drug transporters may be involved in JPH203 hepatic elimination, and to estimate
Hypothalamic neurons regulate body homeostasis by sensing and integrating changes in the levels of key hormones and primary nutrients (amino acids, glucose, and lipids). However, the molecular mechanisms that enable hypothalamic neurons to detect primary nutrients remain elusive. Here, we
International journal of molecular sciences, 22(20) (2021-10-24)
The l-type amino acid transporter 1 (LAT1) is a membranous transporter that transports neutral amino acids for cells and is dysregulated in various types of cancer. Here, we first observed increased LAT1 expression in pemetrexed-resistant non-small cell lung cancer (NSCLC)
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