An anti-ASCT2 monoclonal antibody suppresses gastric cancer growth by inducing oxidative stress and antibody dependent cellular toxicity in preclinical models.

Glutamine is a major nutrient for cancer cells during rapid proliferation. Alanine-serine-cysteine (ASC) transporter 2 (ASCT2; SLC1A5) mediates glutamine uptake in a variety of cancer cells. We previously reported that KM8094, a novel anti-ASCT2 humanized monoclonal antibody, possesses anti-tumor efficacy in gastric cancer patient-derived xenografts.

Synthetic studies on selective adenosine A2A receptor antagonists. Part II: synthesis and structure-activity relationships of novel benzofuran derivatives.

Based on the previously reported lead compound, a series of benzofuran derivatives were prepared to study their antagonistic activities to A(2A) receptor. The replacement of the phenyl group at the 4-position with a heterocyclic ring improved the PK profile and aqueous solubility. From these studies, we discovered a potent new A(2A) antagonist, 12a, which has both a good oral bioavailability and in vivo efficacy on motor disability in MPTP-treated common marmosets.

Synthetic studies on selective adenosine A2A receptor antagonists: synthesis and structure-activity relationships of novel benzofuran derivatives.

A series of benzofuran derivatives were prepared to study their antagonistic activities to the A(2A) receptor. Replacement of the ester group of the lead compound 1 with phenyl ring improved the PK profile, while modifications of the amide moiety showed enhanced antagonistic activity. From these studies, compounds 13c, 13f, and 24a showed good potency in vitro and were identified as novel A(2A) receptor antagonists suitable for oral activity evaluation in animal models of catalepsy.

Localization of organic anion transporting polypeptide 3 (oatp3) in mouse brain parenchymal and capillary endothelial cells.

Organic anion transporting polypeptide 3 (oatp3) transports various CNS-acting endogenous compounds, including thyroid hormones and prostaglandin E2, between extra- and intracellular spaces, suggesting a possible role in CNS function. The purpose of this study was to clarify the expression and localization of oatp3 in the mouse brain. RT-PCR analysis revealed that oatp3 mRNA is expressed in brain capillary-rich fraction, conditionally immortalized brain capillary endothelial cells, choroid plexus, brain and lung, but not in liver or kidney, where oatp1, 2 and 5 mRNAs were detected.

In vitro study of the functional expression of organic anion transporting polypeptide 3 at rat choroid plexus epithelial cells and its involvement in the cerebrospinal fluid-to-blood transport of estrone-3-sulfate.

The cerebrospinal fluid-to-blood efflux transport of estrone-3-sulfate (E(1)S) via the blood-cerebrospinal fluid barrier (BCSFB) may play an important role in regulating E(1)S levels in the brain. Here, we investigated the efflux transport of E(1)S at the BCSFB using conditionally immortalized rat choroid plexus epithelial cells (TR-CSFB) and identified the responsible transporter. The [(3)H]E(1)S uptake by TR-CSFB cells was composed of saturable and nonsaturable components, and the K(m) and V(max) values of the saturable component were determined to be 16.