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Molecular basis of subtype-specific channel regulation using novel ryanodine receptor modulators

Research Project

Project/Area Number 19H03404
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Review Section Basic Section 48020:Physiology-related
Research InstitutionJuntendo University

Principal Investigator

Murayama Takashi  順天堂大学, 医学部, 先任准教授 (10230012)

Co-Investigator(Kenkyū-buntansha) 呉林 なごみ  順天堂大学, 医学部, 客員准教授 (50133335)
小林 琢也  順天堂大学, 医学部, 助教 (60468585)
小川 治夫  京都大学, 薬学研究科, 准教授 (40292726)
井上 華  東京医科大学, 医学部, 講師 (20390700)
冨田 拓郎 (沼賀拓郎)  信州大学, 学術研究院医学系, 准教授 (60705060)
Project Period (FY) 2019-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥17,550,000 (Direct Cost: ¥13,500,000、Indirect Cost: ¥4,050,000)
Fiscal Year 2021: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2019: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Keywordsリアノジン受容体 / カルシウムチャネル / 興奮収縮連関 / 小胞体 / サブタイプ / 骨格筋 / 悪性高熱症 / 筋小胞体 / 構造解析 / 創薬 / 機能解析 / カルシウムイオン / イオンチャネル / クライオ電子顕微鏡
Outline of Research at the Start

リアノジン受容体(RyR)は小胞体膜の超巨大Ca2+遊離チャネルで、細胞内Ca2+調節機構に重要な役割を果たしている。RyRには機能と制御機構が異なる3種類のサブタイプが存在するが、その分子基盤については不明である。申請者らは独自のスクリーニング技術により、サブタイプ選択的RyR作用薬を網羅的に同定することに成功した。本研究では、これらの薬物の作用機序を解析し、結合部位とその構造変化を同定することにより、サブタイプ特異的制御機構を原子レベルで解明する。本研究の成果はRyRチャネル制御機構の構造基盤の理解を深めるとともに、創薬にも直結するため社会的にも大きな意義を持つ。

Outline of Final Research Achievements

To understand the subtype-specific regulation of the ryanodine receptor (RyR), we identified subtype-selective drugs and evaluated their mechanisms of action. We also elucidated the molecular basis of the RyR channel opening mechanism. Novel RyR1- and RyR2-selective inhibitors were identified by an ER Ca2+-based screening method. Their binding domains were determined using RyR1/RyR2 chimeras and the amino acid residues in the binding sites were identified. In addition, the mechanism of channel opening of RyR2 by Ca2+ was elucidated at the atomic level by cryo-EM and mutant functional analysis.

Academic Significance and Societal Importance of the Research Achievements

本研究では新規のRyR1およびRyR2選択的阻害薬を同定することに成功した。これらは機能解析および構造解析の両方に利用でき、サブタイプ特異的制御機構を解明する有用なツールになることが期待される。さらに、クライオ電子顕微鏡法と疾患変異体の網羅的機能解析を組み合わせることで、RyR2のCa2+によるチャネル開口機構を世界で初めて原子レベルで明らかにした。これはIP3受容体や他のリガンド作動性チャネルの動作原理にも応用可能な、イオンチャネル研究における大きな一歩である。今後の研究によりサブタイプ特異的動作機構の解明及び治療薬開発が大きく加速することが期待される。

Report

(4 results)
  • 2022 Final Research Report ( PDF )
  • 2021 Annual Research Report
  • 2020 Annual Research Report
  • 2019 Annual Research Report
  • Research Products

    (49 results)

All 2022 2021 2020 2019 Other

All Int'l Joint Research (7 results) Journal Article (25 results) (of which Int'l Joint Research: 9 results,  Peer Reviewed: 25 results,  Open Access: 24 results) Presentation (14 results) Patent(Industrial Property Rights) (3 results) (of which Overseas: 2 results)

  • [Int'l Joint Research] Virginia Commonwealth University/Mount Sinai Medical Center(米国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] University of Leeds(英国)

    • Related Report
      2021 Annual Research Report
  • [Int'l Joint Research] Virginia Commonwealth University/Mount Sinai Medical Center(米国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] University of Leeds(英国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] 天津大学(中国)

    • Related Report
      2020 Annual Research Report
  • [Int'l Joint Research] Virginia Commonwealth University/Ohio State University/Mount Sinai Medical Center(米国)

    • Related Report
      2019 Annual Research Report
  • [Int'l Joint Research] University of Leeds(英国)

    • Related Report
      2019 Annual Research Report
  • [Journal Article] A reconstituted depolarization-induced Ca2+ release platform for validation of skeletal muscle disease mutations and drug discovery2022

    • Author(s)
      Murayama Takashi、Kurebayashi Nagomi、Numaga-Tomita Takuro、Kobayashi Takuya、Okazaki Satoru、Yamashiro Kyosuke、Nakada Tsutomu、Mori Shuichi、Ishida Ryosuke、Kagechika Hiroyuki、Yamada Mitsuhiko、Sakurai Takashi
    • Journal Title

      Journal of General Physiology

      Volume: 154 Issue: 12

    • DOI

      10.1085/jgp.202213230

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Development of a water-soluble ryanodine receptor 1 inhibitor2022

    • Author(s)
      Ishida Ryosuke、Mori Shuichi、Murayama Takashi、Nakamichi Ayaka、Chai Xikun、Kurebayashi Nagomi、Iinuma Hiroto、Kagechika Hiroyuki
    • Journal Title

      Bioorganic & Medicinal Chemistry

      Volume: 74 Pages: 117027-117027

    • DOI

      10.1016/j.bmc.2022.117027

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Mice with R2509C-RYR1 mutation exhibit dysfunctional Ca2+ dynamics in primary skeletal myocytes2022

    • Author(s)
      Tsuboi Yoshitaka、Oyama Kotaro、Kobirumaki-Shimozawa Fuyu、Murayama Takashi、Kurebayashi Nagomi、Tachibana Toshiaki、Manome Yoshinobu、Kikuchi Emi、Noguchi Satoru、Inoue Takayoshi、Inoue Yukiko U.、Nishino Ichizo、Mori Shuichi、Ishida Ryosuke、Kagechika Hiroyuki、Suzuki Madoka、Fukuda Norio、Yamazawa Toshiko
    • Journal Title

      Journal of General Physiology

      Volume: 154 Issue: 11

    • DOI

      10.1085/jgp.202213136

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Heat-hypersensitive mutants of ryanodine receptor type 1 revealed by microscopic heating2022

    • Author(s)
      Oyama Kotaro、Zeeb Vadim、Yamazawa Toshiko、Kurebayashi Nagomi、Kobirumaki-Shimozawa Fuyu、Murayama Takashi、Oyamada Hideto、Noguchi Satoru、Inoue Takayoshi、Inoue Yukiko U.、Nishino Ichizo、Harada Yoshie、Fukuda Norio、Ishiwata Shin’ichi、Suzuki Madoka
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 119 Issue: 32

    • DOI

      10.1073/pnas.2201286119

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Molecular mechanism of the severe MH/CCD mutation Y522S in skeletal ryanodine receptor (RyR1) by cryo-EM2022

    • Author(s)
      Iyer Kavita A.、Hu Yifan、Klose Thomas、Murayama Takashi、Sams? Montserrat
    • Journal Title

      Proceedings of the National Academy of Sciences

      Volume: 119 Issue: 30

    • DOI

      10.1073/pnas.2122140119

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Molecular basis for gating of cardiac ryanodine receptor explains the mechanisms for gain- and loss-of function mutations2022

    • Author(s)
      Kobayashi Takuya、Tsutsumi Akihisa、Kurebayashi Nagomi、Saito Kei、Kodama Masami、Sakurai Takashi、Kikkawa Masahide、Murayama Takashi、Ogawa Haruo
    • Journal Title

      Nature Communications

      Volume: 13 Issue: 1 Pages: 2821-2821

    • DOI

      10.1038/s41467-022-30429-x

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Cytosolic Ca2+-dependent Ca2+ release activity primarily determines the ER Ca2+ level in cells expressing the CPVT-linked mutant RYR22022

    • Author(s)
      Kurebayashi Nagomi、Murayama Takashi、Ota Ryosaku、Suzuki Junji、Kanemaru Kazunori、Kobayashi Takuya、Ohno Seiko、Horie Minoru、Iino Masamitsu、Yamashita Fumiyoshi、Sakurai Takashi
    • Journal Title

      Journal of General Physiology

      Volume: 154 Issue: 9

    • DOI

      10.1085/jgp.202112869

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Sudden death after inappropriate shocks of implantable cardioverter defibrillator in a catecholaminergic polymorphic ventricular tachycardia case with a novel RyR2 mutation2021

    • Author(s)
      Itoh Hideki、Murayama Takashi、Kurebayashi Nagomi、Ohno Seiko、Kobayashi Takuya、Fujii Yusuke、Watanabe Masaya、Ogawa Haruo、Anzai Toshihisa、Horie Minoru
    • Journal Title

      Journal of Electrocardiology

      Volume: 69 Pages: 111-118

    • DOI

      10.1016/j.jelectrocard.2021.09.015

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Ryanodine Receptor as a Sensor for Intracellular Environments in Muscles2021

    • Author(s)
      Kobayashi Takuya、Kurebayashi Nagomi、Murayama Takashi
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 22 Issue: 19 Pages: 10795-10795

    • DOI

      10.3390/ijms221910795

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Loss-of-function mutations in cardiac ryanodine receptor channel cause various types of arrhythmias including long QT syndrome2021

    • Author(s)
      Hirose Sayako、Murayama Takashi、Tetsuo Naoyuki、Hoshiai Minako、Kise Hiroaki、Yoshinaga Masao、Aoki Hisaaki、Fukuyama Megumi、Wuriyanghai Yimin、Wada Yuko、Kato Koichi、Makiyama Takeru、Kimura Takeshi、Sakurai Takashi、Horie Minoru、Kurebayashi Nagomi、Ohno Seiko
    • Journal Title

      EP Europace

      Volume: 24 Issue: 3 Pages: 497-510

    • DOI

      10.1093/europace/euab250

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The zinc-binding motif of TRPM7 acts as an oxidative stress sensor to regulate its channel activity2021

    • Author(s)
      Hana Inoue, Takashi Murayama, Takuya Kobayashi, Masato Konishi, and Utako Yokoyama
    • Journal Title

      Journal of General Physiology

      Volume: 153 Issue: 6

    • DOI

      10.1085/jgp.202012708

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Differential effects of the formin inhibitor SMIFH2 on contractility and Ca 2+ handling in frog and mouse cardiomyocytes2021

    • Author(s)
      Sakata Koji、Matsuyama Sho、Kurebayashi Nagomi、Hayamizu Kengo、Murayama Takashi、Nakamura Kunihide、Kitamura Kazuo、Morimoto Sachio、Takeya Ryu
    • Journal Title

      Genes to Cells

      Volume: 26 Issue: 8 Pages: 583-595

    • DOI

      10.1111/gtc.12873

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Inhibition of endothelin A receptor by a novel, selective receptor antagonist enhances morphine-induced analgesia: Possible functional interaction of dimerized endothelin A and μ-opioid receptors. Biomed Pharmacother.2021

    • Author(s)
      Kuroda Y, Nonaka M, Kamikubo Y, Ogawa H, Murayama T, Kurebayashi N, Sakairi H, Miyano K, Komatsu A, Dodo T, Nakano-Ito K, Yamaguchi K, Sakurai T, Iseki M, Hayashida M, Uezono Y
    • Journal Title

      Biomed Pharmacother.

      Volume: 141 Pages: 111800-111800

    • DOI

      10.1016/j.biopha.2021.111800

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] A novel RyR1-selective inhibitor prevents and rescues sudden death in mouse models of malignant hyperthermia and heat stroke2021

    • Author(s)
      Yamazawa Toshiko、Kobayashi Takuya、Kurebayashi Nagomi、Konishi Masato、Noguchi Satoru、Inoue Takayoshi、Inoue Yukiko U.、et al.
    • Journal Title

      Nature Communications

      Volume: 12 Issue: 1 Pages: 4293-4293

    • DOI

      10.1038/s41467-021-24644-1

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Purification of Recombinant Wild Type and Mutant Ryanodine Receptors Expressed in HEK293 Cells2021

    • Author(s)
      Hu Yifan、Iyer Kavita、Nayak Ashok、Kurebayashi Nagomi、Murayama Takashi、Samso Montserrat
    • Journal Title

      BIO-PROTOCOL

      Volume: 11 Issue: 15

    • DOI

      10.21769/bioprotoc.4112

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Co-Phenotype of Left Ventricular Non-Compaction Cardiomyopathy and Atypical Catecholaminergic Polymorphic Ventricular Tachycardia in Association With R169Q, a <i>Ryanodine Receptor Type 2</i> Missense Mutation2020

    • Author(s)
      Nozaki Y, Kato Y, Uike K, Yamamura K, Kikuchi M, Yasuda M, Ohno S, Horie M, Murayama T, Kurebayashi N, Horigome H
    • Journal Title

      Circulation Journal

      Volume: 84 Issue: 2 Pages: 226-234

    • DOI

      10.1253/circj.CJ-19-0720

    • NAID

      130007789920

    • ISSN
      1346-9843, 1347-4820
    • Year and Date
      2020-01-24
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Structural basis for diamide modulation of ryanodine receptor2020

    • Author(s)
      Ma Ruifang、Haji-Ghassemi Omid、Ma Dan、Jiang Heng、Lin Lianyun、Yao Li、Samurkas Arthur、Li Yuxin、Wang Yiwen、Cao Peng、Wu Shian、Zhang Yan、Murayama Takashi、Moussian Bernard、Van Petegem Filip、Yuchi Zhiguang
    • Journal Title

      Nature Chemical Biology

      Volume: 16 Issue: 11 Pages: 1246-1254

    • DOI

      10.1038/s41589-020-0627-5

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Structural mechanism of two gain-of-function cardiac and skeletal RyR mutations at an equivalent site by cryo-EM2020

    • Author(s)
      Iyer Kavita A.、Hu Yifan、Nayak Ashok R.、Kurebayashi Nagomi、Murayama Takashi、Sams? Montserrat
    • Journal Title

      Science Advances

      Volume: 6 Issue: 31 Pages: 0-0

    • DOI

      10.1126/sciadv.abb2964

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Conformational diversity of dynactin sidearm and domain organization of its subunit p150.2020

    • Author(s)
      Kei Saito, Takashi Murayama, Tomone Hata, Takuya Kobayashi, Keitaro Shibata, Saiko Kazuno, Tsutomu Fujimura, Takashi Sakurai, and Yoko Y. Toyoshima
    • Journal Title

      Molecular Biology of the Cell

      Volume: - Issue: 12 Pages: 1218-1231

    • DOI

      10.1091/mbc.e20-01-0031

    • Related Report
      2020 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] TRIC-A Channel Maintains Store Calcium Handling by Interacting With Type 2 Ryanodine Receptor in Cardiac Muscle2020

    • Author(s)
      Zhou X, Park KH, Yamazaki D, Lin PH, Nishi M, Ma Z, Qiu L, Murayama T, Zou X, Takeshima H, Zhou J, Ma J.
    • Journal Title

      Circulation Reserach

      Volume: 126 Issue: 4 Pages: 417-435

    • DOI

      10.1161/circresaha.119.316241

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Insights into channel modulation mechanism of RYR1 mutants using Ca2+ imaging and molecular dynamics2020

    • Author(s)
      Yamazawa Toshiko、Ogawa Haruo、Murayama Takashi、Yamaguchi Maki、Oyamada Hideto、Suzuki Junji、Kurebayashi Nagomi、Kanemaru Kazunori、Oguchi Katsuji、Sakurai Takashi、Iino Masamitsu
    • Journal Title

      The Journal of General Physiology

      Volume: 152 Issue: 1 Pages: 0-0

    • DOI

      10.1085/jgp.201812235

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Regulatory mechanisms of ryanodine receptor/Ca2+ release channel revealed by recent advancements in structural studies2020

    • Author(s)
      Ogawa Haruo、Kurebayashi Nagomi、Yamazawa Toshiko、Murayama Takashi
    • Journal Title

      Journal of Muscle Research and Cell Motility

      Volume: in press Issue: 2 Pages: 0-0

    • DOI

      10.1007/s10974-020-09575-6

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] RyR2 mutation-linked arrhythmogenic diseases and its therapeutic strategies2020

    • Author(s)
      Kurebayashi Nagomi、Murayama Takashi
    • Journal Title

      Folia Pharmacologica Japonica

      Volume: 155 Issue: 4 Pages: 225-229

    • DOI

      10.1254/fpj.20017

    • NAID

      130007867553

    • ISSN
      0015-5691, 1347-8397
    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Assays for Modulators of Ryanodine Receptor (RyR)/Ca 2+ Release Channel Activity for Drug Discovery for Skeletal Muscle and Heart Diseases2019

    • Author(s)
      Murayama Takashi、Kurebayashi Nagomi
    • Journal Title

      Current Protocols in Pharmacology

      Volume: 87 Issue: 1 Pages: 0-0

    • DOI

      10.1002/cpph.71

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Structural development of a type-1 ryanodine receptor (RyR1) Ca2+-release channel inhibitor guided by endoplasmic reticulum Ca2+ assay2019

    • Author(s)
      Mori Shuichi、Iinuma Hiroto、Manaka Noriaki、Ishigami-Yuasa Mari、Murayama Takashi、Nishijima Yoshiaki、Sakurai Akiko、Arai Ryota、Kurebayashi Nagomi、Sakurai Takashi、Kagechika Hiroyuki
    • Journal Title

      European Journal of Medicinal Chemistry

      Volume: 179 Pages: 837-848

    • DOI

      10.1016/j.ejmech.2019.06.076

    • Related Report
      2019 Annual Research Report
    • Peer Reviewed
  • [Presentation] 骨格筋脱分極誘発性Ca2+遊離(DICR)再構成系の開発2022

    • Author(s)
      村山 尚、呉林 なごみ、冨田(沼賀)拓郎、小林 琢也、中田 勉、山田 充彦、櫻井 隆
    • Organizer
      第8回日本筋学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 骨格筋疾患治療薬開発のための脱分極誘発性Ca2+遊離再構成プラットフォームの構築2022

    • Author(s)
      村山 尚、呉林 なごみ、冨田(沼賀)拓郎、小林 琢也、中田 勉、石田 良典、森 修一、影近 弘之、山田 充彦、櫻井 隆
    • Organizer
      第96回日本薬理学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 骨格筋脱分極誘発性Ca2+遊離(DICR)再構成系を用いた筋疾患へのアプローチ2021

    • Author(s)
      村山 尚、呉林 なごみ、小林 琢也、岡﨑 諭、山代 暁介、櫻井 隆
    • Organizer
      第7回日本筋学会学術集会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 骨格筋脱分極誘発性Ca2+遊離超分子複合体の再構成2021

    • Author(s)
      村山 尚
    • Organizer
      第95回日本薬理学会年会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 骨格筋興奮収縮連関の再構成2021

    • Author(s)
      村山 尚
    • Organizer
      第99回日本生理学会合同大会
    • Related Report
      2021 Annual Research Report
  • [Presentation] 新規1型リアノジン受容体(RyR1)阻害剤の結合部位の同定.2021

    • Author(s)
      村山 尚、呉林 なごみ、小林 琢也、小川 治夫、児玉 昌美、森 修一、影近 弘之、櫻井 隆.
    • Organizer
      第94回日本薬理学会年会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 1型リアノジン受容体チャネル複合体関連筋疾患の発症機構と治療戦略.2021

    • Author(s)
      村山 尚
    • Organizer
      第126回日本解剖学会・第98回日本生理学会合同大会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 新規1型リアノジン受容体(RyR1)阻害薬の結合部位の探索.2020

    • Author(s)
      村山 尚、呉林 なごみ、小林 琢也、小川 治夫、児玉 昌美、森 修一、影近 弘之、櫻井 隆.
    • Organizer
      第143回日本薬理学会関東部会
    • Related Report
      2020 Annual Research Report
  • [Presentation] 小胞体内Ca2+濃度測定により新たに同定されたRyR1選択的阻害剤の性質の検討.2020

    • Author(s)
      松川 紘之、村山 尚、小林 琢也、呉林 なごみ、山澤 徳志子、湯浅 磨里、森 修一、影近 弘之、櫻井 隆.
    • Organizer
      第6回日本筋学会学術集会
    • Related Report
      2020 Annual Research Report
  • [Presentation] Therapeutic effects of a novel RyR1 inhibitor on malignant hyperthermia model mice.2020

    • Author(s)
      Murayama T, Yamazawa T, Kobayashi T, Kurebayashi N, Noguchi S, Nishino N, Mori S, Kagechika H, Lopez JR, Allen PD, Sakurai T.
    • Organizer
      Biophysical Society 64th Annual Meeting
    • Related Report
      2019 Annual Research Report
  • [Presentation] Characterization of novel RyR1-selective inhibitors identified by high-throughput screening using ER Ca2+ measurement.2020

    • Author(s)
      Matsukawa H, Murayama T, Kobayashi T, Kurebayashi N, Yamazawa T, Ishigami-Yuasa M, Mori S, Kagechika H, Sakurai T.
    • Organizer
      Biophysical Society 64th Annual Meeting
    • Related Report
      2019 Annual Research Report
  • [Presentation] 新規RyR1抑制薬の悪性高熱症モデルマウスに対する効果.2020

    • Author(s)
      村山 尚,山澤 徳志子,小林 琢也,呉林 なごみ,野口 悟,西野 一三,森 修一,影近 弘之,Jose R. Lopez,Paul D. Allen,櫻井 隆.
    • Organizer
      第93回日本薬理学会年会
    • Related Report
      2019 Annual Research Report
  • [Presentation] 悪性高熱症モデルマウスを用いた新規RyR1阻害薬の治療効果の検討.2019

    • Author(s)
      村山 尚、山澤 徳志子、小林 琢也、呉林 なごみ、野口 悟、井上 高良、井上 由紀子、森 修一、飯沼 大翔、間中 紀暁、湯浅 磨里、影近 弘之、西野 一三、櫻井 隆.
    • Organizer
      第5回日本筋学会学術集会
    • Related Report
      2019 Annual Research Report
  • [Presentation] リアノジン受容体チャネル制御機構への構造・機能学的アプローチ.2019

    • Author(s)
      村山 尚
    • Organizer
      第92回日本生化学会大会
    • Related Report
      2019 Annual Research Report
  • [Patent(Industrial Property Rights)] 2型リアノジン受容体活性抑制剤2021

    • Inventor(s)
      國廣なごみ、村山尚、影近弘之、森修一、湯浅磨里、飯沼大翔
    • Industrial Property Rights Holder
      学校法人順天堂、国立大学法人東京医科歯科大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2021 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 2型リアノジン受容体活性抑制剤2021

    • Inventor(s)
      國廣なごみ、村山尚、影近弘之、森修一、湯浅磨里、飯沼大翔
    • Industrial Property Rights Holder
      学校法人順天堂、国立大学法人東京医科歯科大学
    • Industrial Property Rights Type
      特許
    • Filing Date
      2021
    • Related Report
      2020 Annual Research Report
    • Overseas
  • [Patent(Industrial Property Rights)] 2型リアノジン受容体活性抑制剤2020

    • Inventor(s)
      國廣なごみ、村山尚、影近弘之、森修一、湯浅磨里、飯沼大翔
    • Industrial Property Rights Holder
      学校法人順天堂、国立大学法人東京医科歯科大学
    • Industrial Property Rights Type
      特許
    • Industrial Property Number
      2020-020656
    • Filing Date
      2020
    • Related Report
      2019 Annual Research Report

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Published: 2019-04-18   Modified: 2024-01-30  

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