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Searching for endogenous substrates of organic cation transporters by selective metabolomics

Research Project

Project/Area Number 18K06745
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Review Section Basic Section 47060:Clinical pharmacy-related
Research InstitutionKanazawa University

Principal Investigator

Masuo Yusuke  金沢大学, 薬学系, 助教 (90708140)

Project Period (FY) 2018-04-01 – 2021-03-31
Project Status Completed (Fiscal Year 2020)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsメタボローム解析 / 有機カチオン膜輸送体 / バイオマーカー / 膜輸送体 / メタボロミクス / 生体内基質
Outline of Final Research Achievements

Organic cation transporters (OCTs) are involved in hepatic and renal distribution of various substrates, and may be primarily involved in pharmacokinetics of some substrate drugs. The aim of the present study is to search endogenous OCTs substrates. According to the untargeted metabolome analysis, plasma concentration of some acylcarnitines in OCT’s inhibitors treated mice were higher than that in vehicle-treated mice. Efflux of acetylcarnitine was also observed in from oocytes expressing OCT1. Thus, acylcarnitines were presumably endogenous OCT1 substrates although the role of OCTs in their tissue distribution should be further evaluated.

Academic Significance and Societal Importance of the Research Achievements

膜輸送体OCTsの輸送機能は、先天的・後天的な要因で個人差があり、輸送機能をin vivoで個人毎に予測することは、薬物治療上重要である。OCTsの生体内基質は、その血漿中濃度を測定することで、薬物相互作用または個人差に起因するOCTs輸送活性の変化をin vivoで予測可能にし、OCTs基質薬による適切な薬物治療を可能にする。本研究で同定したバイオマーカー候補として、血漿中acylcarnitine濃度は、薬物相互作用予測や、機能変化時の適切な基質薬の投与量設計に応用できる。

Report

(4 results)
  • 2020 Annual Research Report   Final Research Report ( PDF )
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (39 results)

All 2021 2020 2019 2018 Other

All Journal Article (15 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 15 results,  Open Access: 5 results) Presentation (23 results) (of which Int'l Joint Research: 10 results,  Invited: 3 results) Remarks (1 results)

  • [Journal Article] Effects of probenecid on hepatic and renal disposition of hexadecanedioate, an endogenous substrate of Organic anion transporting polypeptide 1b in rats.2021

    • Author(s)
      Futatsugi A, Masuo Y, Kato Y
    • Journal Title

      J Pharm Sci

      Volume: - Issue: 5 Pages: 2274-2284

    • DOI

      10.1016/j.xphs.2021.02.011

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] 6-Hydroxyindole is an endogenous long-lasting OATP1B1 inhibitor elevated in renal failure patients2020

    • Author(s)
      Masuo Yusuke、Fujita Ken-ichi、Mishiro Kenji、Seba Natsumi、Kogi Tatsuya、Okumura Hidenori、Matsumoto Natsumi、Kunishima Munetaka、Kato Yukio
    • Journal Title

      Drug Metabolism and Pharmacokinetics

      Volume: 35 Issue: 6 Pages: 555-562

    • DOI

      10.1016/j.dmpk.2020.09.001

    • NAID

      50014656616

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Homostachydrine is a Xenobiotic Substrate of OCTN1/SLC22A4 and Potentially Sensitizes Pentylenetetrazole-Induced Seizures in Mice2020

    • Author(s)
      Nishiyama Misa、Nakamichi Noritaka、Yoshimura Tomoyuki、Masuo Yusuke、Komori Tomoe、Ishimoto Takahiro、Matsuo Jun-ichi、Kato Yukio
    • Journal Title

      Neurochemical Research

      Volume: 45 Issue: 11 Pages: 2664-2678

    • DOI

      10.1007/s11064-020-03118-8

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Static Model?Based Assessment of OATP1B1-Mediated Drug Interactions with Preincubation-Dependent Inhibitors Based on Inactivation and Recovery Kinetics2020

    • Author(s)
      Taguchi Takayuki、Masuo Yusuke、Futatsugi Azusa、Kato Yukio
    • Journal Title

      Drug Metabolism and Disposition

      Volume: 48 Issue: 9 Pages: 750-758

    • DOI

      10.1124/dmd.120.000020

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Oral Administration of the Food Derived Hydrophilic Antioxidant Ergothioneine Enhances Object Recognition Memory in Mice2020

    • Author(s)
      Nakamichi N, Nakao S, Nishiyama M, Takeda Y, Ishimoto T, Masuo Y, Matsumoto S, Suzuki M, Kato Y.
    • Journal Title

      Curr Mol Pharmacol

      Volume: - Issue: 2 Pages: 220-233

    • DOI

      10.2174/1874467213666200212102710

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Higher Systemic Exposure to Unbound Active Metabolites of Regorafenib Is Associated With Short Progression-Free Survival in Colorectal Cancer Patients.2020

    • Author(s)
      Kubota Y, Fujita KI, Takahashi T, Sunakawa Y, Ishida H, Hamada K, Ichikawa W, Tsunoda T, Shimada K, Masuo Y, Kato Y, Sasaki Y.
    • Journal Title

      Clin Pharmacol Ther

      Volume: - Issue: 3 Pages: 586-595

    • DOI

      10.1002/cpt.1810

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Maturational Characterization of Mouse Cortical Neurons Three-Dimensionally Cultured in Functional Polymer FP001-Containing Medium2019

    • Author(s)
      Nakamichi N, Matsumoto Y, Kawanishi T, Ishimoto T, Masuo Y, Horikawa M, Kato Y
    • Journal Title

      Biological and Pharmaceutical Bulletin

      Volume: 42 Issue: 9 Pages: 1545-1553

    • DOI

      10.1248/bpb.b19-00307

    • NAID

      130007700083

    • ISSN
      0918-6158, 1347-5215
    • Year and Date
      2019-09-01
    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Short-lasting Inhibition of Hepatic Uptake Transporter OATP1B1 by Tyrosine Kinase Inhibitor Pazopanib2019

    • Author(s)
      Taguchi T, Masuo Y, Sakai Y, Kato Y.
    • Journal Title

      Drug Metab Pharmacokinet

      Volume: 34 Issue: 6 Pages: 372-379

    • DOI

      10.1016/j.dmpk.2019.08.001

    • NAID

      50014558527

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Metabolome Analysis Reveals Dermal Histamine Accumulation in Murine Dermatitis Provoked by Genetic Deletion of P-Glycoprotein and Breast Cancer Resistance Protein2019

    • Author(s)
      Hashimoto N, Nakamichi N, Nanmo H, Kimura KI, Masuo Y, Sakai Y, Schinkel AH, Sato S, Soga T, Kato Y
    • Journal Title

      Pharm Res

      Volume: 36 Issue: 11 Pages: 158-158

    • DOI

      10.1007/s11095-019-2695-3

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Bile Duct Obstruction Leads to Increased Intestinal Expression of Breast Cancer Resistance Protein With Reduced Gastrointestinal Absorption of Imatinib.2019

    • Author(s)
      Kawanishi T, Arakawa H, Masuo Y, Nakamichi N, Kato Y
    • Journal Title

      J Pharm Sci

      Volume: 108 Issue: 9 Pages: 3130-3137

    • DOI

      10.1016/j.xphs.2019.05.017

    • Related Report
      2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hydrolyzed Salmon Milt Extract Enhances Object Recognition and Location Memory Through an Increase in Hippocampal Cytidine Nucleoside Levels in Normal Mice2019

    • Author(s)
      Nakamichi Noritaka、Nakao Shunsuke、Masuo Yusuke、Koike Ayaka、Matsumura Naoto、Nishiyama Misa、Al-Shammari Aya Hasan、Sekiguchi Hirotaka、Sutoh Keita、Usumi Koji、Kato Yukio
    • Journal Title

      Journal of Medicinal Food

      Volume: 22 Issue: 4 Pages: 408-415

    • DOI

      10.1089/jmf.2018.4285

    • Related Report
      2019 Research-status Report 2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Pazopanib Interacts With Irinotecan by Inhibiting UGT1A1-mediated Glucuronidation, but Not OATP1B1-mediated Hepatic Uptake, of an Active Metabolite SN-382019

    • Author(s)
      Iwase M, Fujita KI, Nishimura Y, Seba N, Masuo Y, Ishida H, Kato Y, Kiuchi Y
    • Journal Title

      Cancer Chemother Pharmacol.

      Volume: 83 Issue: 5 Pages: 993-998

    • DOI

      10.1007/s00280-019-03784-8

    • Related Report
      2019 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Influx and efflux transporters contribute to the increased dermal exposure to active metabolite of regorafenib after repeated oral administration2019

    • Author(s)
      Al-Shammari AH, Masuo Y, Fujita K, Yoshikawa Y, Nakamichi N, Kubota Y, Sasaki Y, Kato Y
    • Journal Title

      J Pharm Sci.

      Volume: 印刷中 Issue: 6 Pages: 2173-2179

    • DOI

      10.1016/j.xphs.2019.01.018

    • Related Report
      2018 Research-status Report
    • Peer Reviewed
  • [Journal Article] Ergothioneine-induced neuronal differentiation is mediated through activation of S6K1 and neurotrophin 4/5-TrkB signaling in murine neural stem cells2019

    • Author(s)
      Ishimoto T, Masuo Y, Kato Y, Nakamichi N
    • Journal Title

      Cell Signal.

      Volume: 53 Pages: 269-280

    • DOI

      10.1016/j.cellsig.2018.10.012

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Journal Article] Combination Metabolomics Approach for Identifying Endogenous Substrates of Carnitine/Organic Cation Transporter OCTN12018

    • Author(s)
      Masuo Y, Ohba Y, Yamada K, Al-Shammari AH, Seba N, Nakamichi N, Ogihara T, Kunishima M, Kato Y
    • Journal Title

      Pharm Res.

      Volume: 35 Issue: 11 Pages: 224-224

    • DOI

      10.1007/s11095-018-2507-1

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 有効腎血漿流量の評価に応用可能な生体内化合物の網羅的探索2021

    • Author(s)
      及川夏月、増尾友佑、三代憲司、国嶋崇隆、加藤 将夫
    • Organizer
      日本薬学会第141年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 高分子DNAはpyrimidine nucleosideとして消化管吸収される2020

    • Author(s)
      増尾友佑、小池彩花、石本尚大、加藤将夫
    • Organizer
      日本薬剤学会第35年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Association between pharmacokinetics and dermal toxicology of tyrosine kinase inhibitors in a mouse model2020

    • Author(s)
      アルシャッマリアヤ、増尾友佑、島田和弘、藤田健一、若山友彦、加藤将夫
    • Organizer
      第35回日本薬物動態学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] チロシンキナーゼ阻害薬による手足症候群と表皮角化細胞への毒性との関連2020

    • Author(s)
      増尾友佑、島田和弘、石本尚大、加藤 将夫
    • Organizer
      日本薬学会第140年会
    • Related Report
      2019 Research-status Report
  • [Presentation] チロシンキナーゼ阻害薬のケラチノサイトにおける分布・毒性と皮膚障害との関連2019

    • Author(s)
      増尾友佑、加藤将夫
    • Organizer
      日本薬物動態学会第34回年会
    • Related Report
      2019 Research-status Report
    • Invited
  • [Presentation] BCRP細胞外領域に対する抗体作製を目指したBCRP発現系の最適化2019

    • Author(s)
      森永真理恵、増尾友佑、石本尚大、鎌田春彦、加藤将夫
    • Organizer
      日本薬物動態学会第34回年会
    • Related Report
      2019 Research-status Report
  • [Presentation] BCRPのin vivoでの輸送機能評価に適用可能なBCRP生体内基質の網羅的探索2019

    • Author(s)
      笹田京佑、増尾友佑、石本尚大、加藤将夫
    • Organizer
      日本薬物動態学会第34回年会
    • Related Report
      2019 Research-status Report
  • [Presentation] チロシンキナーゼ阻害薬による手足症候群の発症機構:表皮角化細胞への毒性との関連2019

    • Author(s)
      島田和弘、増尾友佑、藤田健一、加藤将夫
    • Organizer
      第41回生体膜と薬物の相互作用シンポジウム
    • Related Report
      2019 Research-status Report
  • [Presentation] Identification of endogenous substrates of gastrointestinal inflammation-associated transporters, OCTN1/SLC22A42019

    • Author(s)
      Yusuke Masuo, Yukio Kato
    • Organizer
      The 27th Annual Meeting of The Korean Society of Applied Pharmacology
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research / Invited
  • [Presentation] 妊娠高血圧症候群治療への応用を目指したヒトaminopeptidase A組換えタンパク質の体内動態解析2019

    • Author(s)
      近藤友美、増尾友佑、今村龍、水谷栄彦、松本邦夫、加藤将夫
    • Organizer
      第24回日本病態プロテアーゼ学会学術集会
    • Related Report
      2019 Research-status Report
  • [Presentation] Screening of endogenous OCTs substrates applicable for prediction of drug interactions2019

    • Author(s)
      Yusuke Masuo, Megumi Kato, Shiori Komura, Takahiro Ishimoto, Yukio Kato
    • Organizer
      12th International ISSX Meeting
    • Related Report
      2019 Research-status Report
    • Int'l Joint Research
  • [Presentation] 膜輸送体OCTsのin vivoでの機能評価を目指した内因性基質の網羅的探索2019

    • Author(s)
      増尾友佑、加藤愛、石本尚大、加藤将夫
    • Organizer
      第14回トランスポーター研究会年会
    • Related Report
      2019 Research-status Report
  • [Presentation] マウス単離骨髄細胞へのゲムシタビン取り込み機構の解析2019

    • Author(s)
      田中杏奈、増尾友佑、松本建、加藤将夫
    • Organizer
      日本薬剤学会第34年会
    • Related Report
      2019 Research-status Report
  • [Presentation] Identification of Endogenous Substrates of SLC22A4 by Metabolomic Approach Based on Transporter and Structure Selective Strategies2018

    • Author(s)
      Yusuke Masuo, Yuri Ohba, Kohei Yamada, Noritaka Nakamichi, Munetaka Kunishima, Yukio Kato
    • Organizer
      PharmSci 360 American Association of Pharmaceutical Scientists
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Comparison of Intestinal Absorption of Nucleic Acids: Comprehensive Quantification-based Analysis using Mass Spectrometry2018

    • Author(s)
      Yusuke Masuo, Ayaka Koike, Yukio Kato
    • Organizer
      日本薬物動態学会第33回年会・MDO国際合同学会
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Screening of endogenous OCTs substrates based on in vivo inhibition studies to estimate drug interaction potential2018

    • Author(s)
      Megumi Kato, Yusuke Masuo, Yukio Kato
    • Organizer
      日本薬物動態学会第33回年会・MDO国際合同学会
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Construction of neutralizing antibodies against P-glycoprotein by using antibody phage displays2018

    • Author(s)
      Marie Morinaga, Yusuke Masuo, Takahiro Ishimoto, Noritaka Nakamichi, Haruhiko Kamada, Yukio Kato
    • Organizer
      日本薬物動態学会第33回年会・MDO国際合同学会
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Characterization of effect of rifampicin on disposition of endogenous OATPs substrates in rats2018

    • Author(s)
      Azusa Futatsugi, Yusuke Masuo, Yukio Kato
    • Organizer
      日本薬物動態学会第33回年会・MDO国際合同学会
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Cytotoxic effects of tyrosine kinase inhibitors in keratinocytes and their possible relevance to ABC transporters2018

    • Author(s)
      Kazuhiro Shimada, Yusuke Masuo, Ken-ichi Fujita, Yasutsuna Sasaki, Yukio Kato
    • Organizer
      日本薬物動態学会第33回年会・MDO国際合同学会
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Accumulation of active metabolite of anticancer agent regorafenib involves nonlinear hepatic distribution after repeated dose2018

    • Author(s)
      Aya Hasan, Yusuke Masuo, Ken-ichi Fujita, Yutaro Kubota, Yasutsuna Sasaki, and Yukio Kato
    • Organizer
      日本薬物動態学会第33回年会・MDO国際合同学会
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Optimization of the preincubation period for assessment of OATP1B1 inhibition by preincubation-dependent inhibitors2018

    • Author(s)
      Takayuki Taguchi, Yusuke Masuo, Yoshiyuki Sakai, Yukio Kato
    • Organizer
      日本薬物動態学会第33回年会・MDO国際合同学会
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] 遺伝子欠損マウス臓器を基質源としたメタボローム解析による膜輸送体BCRPの生体内基質探索2018

    • Author(s)
      笹田京佑、増尾友佑、中道範隆、加藤将夫
    • Organizer
      日本薬学会北陸支部第130回例会
    • Related Report
      2018 Research-status Report
  • [Presentation] SLC22A4の生体内基質探索:基質認識特性に基づいた構造選択的メタボロミクスによるアプローチ2018

    • Author(s)
      増尾友佑、加藤将夫
    • Organizer
      第13回トランスポーター研究会年会
    • Related Report
      2018 Research-status Report
    • Invited
  • [Remarks] 金沢大学医薬保健研究域薬学系 分子薬物治療学研究室ホームページ

    • URL

      http://www.p.kanazawa-u.ac.jp/~bunyaku/

    • Related Report
      2019 Research-status Report 2018 Research-status Report

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Published: 2018-04-23   Modified: 2022-01-27  

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