Rapid screening of antineoplastic candidates for the human organic anion transporter OATP1B3 substrates using fluorescent probes
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概要
- 論文の詳細を見る
A rapid screening system has been established to extract novel candidates that exhibit potent inhibition of the transport of fluorescent substrate by organic anion transporting polypeptide (OATP) 1B3. OATP1B3 is abundantly expressed in solid digestive organ cancers. Thus, the identification of new substrates leads to novel strategies for effective cancer chemotherapy with minimal adverse effects. We used an automated image acquisition and analysis system (IN Cell Analyzer 1000) to visualize the transport and subsequent accumulation of the fluorescent substrate chenodeoxycholyl-(Nε-NBD)-lysine (CDCA-NBD). Antineoplastic screening demonstrated that five candidates agents, docetaxel, actinomycin D, mitoxantrone, paclitaxel, and SN-38, exhibited potent inhibitory effects on OATP1B3-mediated transport of CDCA-NBD. To clarify if these antineoplastic drugs are substrates for OATP1B3, we performed transport assays in OATP1B3-expressing cells. We determined that SN-38 is a novel substrate for OATP1B3. In conclusion, our results demonstrate that the screening system established in this study is a useful method for the rapid extraction of candidate therapeutic agents from the large numbers of compounds.
- Elsevierの論文
- 2008-02-18
著者
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Mano Nariyasu
Dep. Of Pharmaceutical Sciences Tohoku Univ. Hospital
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Mano Nariyasu
東北大学 薬研究
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Mano N
Tsukuba Research Laboratories Eisai Co. Ltd.
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HISHINUMA TAKANORI
Division of Pharmacotherapy, Graduate School of Pharmaceutical Sciences, Tohoku University
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Goto J
Tohoku Univ. Sendai Jpn
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Goto J
The Ion Engineering Research Institute Corporation
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Mano N
Dep. Of Pharmaceutical Sciences Tohoku Univ. Hospital
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Unno Michiaki
Department Of Gastroenterological Surgery Tohoku University Graduate School Of Medicine
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Unno Michiaki
Division Of Hepato-biliary-pancreatic Surgery Tohoku University Graduate School Of Medicine
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Unno Michiaki
Division Of Gastroenterological Surgery Department Of Surgery Tohoku University School Of Medicine
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Abe Tadayoshi
Department Of Gastroenterological Surgery Tohoku University Graduate School Of Medicine
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Goto J
Division Of Clinical Pharmacy Graduate School Of Pharmaceutical Sciences Tohoku University
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Mano Nariyasu
Analytical Chemistry And Pharmaceutical Research Section Tsukuba Research Laboratories Eisai Co. Ltd
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Hayashi T
Department Of Pharmacy Fujita Health University Hospital
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Abe Takaaki
Division Of Nephrology Endocrinology And Vascular Medicine Department Of Medicine Tohoku University
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Abe Takaaki
Div. Of Nephrology Endocrinology And Vascular Medicine Tohoku Univ. Graduate School Of Biomedical En
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Unno Michiaki
Div. Of Gastroenterological Surgery Dep. Of Surgery Tohoku Univ. Graduate School Of Medicine
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Aoki Takeshi
Division Of Nephrology Endocrinology And Vascular Medicine Tohoku University Graduate School Of Medi
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Kobayashi Minako
Div. Of Clinical Pharmacy Graduate School Of Pharmaceutical Sciences Tohoku Univ.
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Hishinuma T
Division Of Clinical Pharmacy Graduate School Of Pharmaceutical Sciences Tohoku University
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Goto Junichi
Department of Pharmaceutical Sciences, Tohoku University Hospital
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Okada Masahiro
Division of Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, Tohoku University
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Abe Takaaki
Division of Nephrology, Endocrinology and Vascular Medicine, Tohoku University, Graduate School of Medicine
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Yamaguchi Hiroaki
Department of Pharmaceutical Sciences, Tohoku University Hospital
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