Publications of

Takeda Research Laboratories

2014

December 2015

武田研究業績集 2 0 1 4

武 田 薬 品 工 業 株 式 会 社

Takeda Pharmaceutical Company Limited Osaka, Japan

CONTENTS Originals in English

Analytical Chemistry ................................................................................................................... 1

Organic Chemistry ....................................................................................................................... 2

Medicinal Chemistry .................................................................................................................... 4

Biochemistry and Biotechnology ................................................................................................. 7

Immunology ................................................................................................................................. 8

Pharmacology ............................................................................................................................... 8

Basic Biology and Physiology .................................................................................................... 12

Pharmacokinetics and Drug Metabolism .................................................................................. 16

Drug Safety Evaluation ............................................................................................................. 17

Information Science ................................................................................................................... 18

Technology Development ........................................................................................................... 18

Originals in Japanese

Analytical Chemistry ................................................................................................................. 19

Medicinal Chemistryh ............................................................................................................... 19

Pharmacology ............................................................................................................................. 19

Author Index................................................................................................................. 21

1

Originals in English Analytical Chemistry [T1] Hydrogen/Deuterium Exchange in Parallel with Acid/Base Induced Conformational Change in Electrospray Droplets Kharlamova A, Fisher CM, McLuckey SA

J. Mass. Spectrom. (2014), 49, 437-444. (DOI: 10.1002/jms.3369)

Kharlamova, A.; Fisher, C. M.; McLuckey, S.A

[T2] Ultra Performance Liquid Chromatography Coupled with High Resolution Quantitation Mass Spectrometry Method Development and Validation for Determining Genotoxic 2,5-Dichlorobenzoyl Chloride in MLN9708 Drug Substance Mingkun Fu, Qing Lu, Elizabeth Hewitt, Jun Wang

Journal of Pharmaceutical and Biomedical Analysis 2014; 89C, 233-239.

Mingkun Fu, Qing Lu, Elizabeth Hewitt, Jun Wang

[T3] Rational polymorph screening based on slow cooling crystallization of poorly soluble mebendazole Masatoshi Karashima, Kouya Kimoto, Takashi Kojima, Yukihiro Ikeda

J. of Crystal Growth, 390, 30-37 (2014)

Masatoshi Karashima, Kouya Kimoto, Takashi Kojima, Yukihiro Ikeda

辛島 正俊, 木本 香哉, 小嶌 隆史, 池田 幸弘

[T4] Affecting Protein Charge State Distributions in nano-Electrospray Ionization via In-Spray Solution Mixing using Theta Capillaries. Fisher CM, Kharlamova A, McLuckey SA

Anal. Chem. (2014), 86, 4581-4588. (DOI: 10.1021/ac500721r)

Fisher, C. M.; Kharlamova, A.; McLuckey, S.A

[T5] Solid Form Selection of Highly Solvating TAK-441 Exhibiting Solvate-Trapping Polymorphism Solid Form Selection of Highly Solvating TAK-441 Exhibiting Solvate-Trapping Polymorphism

Cryst. Growth Des., 14 (7), 3335–3342 (2014)

Kentaro Iwata, Takashi Kojima, Yukihiro Ikeda

岩田 健太郎, 小嶌 隆史, 池田 幸弘

2

[T6] Determination of a Low-Level Percent Enantiomer of a compound with No Ultraviolet Chromaphore Using Vibrational Circular Dichroism (VCD): Enantiomeric Purity by VCD of a Compound with three chiral centers Kott L, Petrovic J, Phelps D, Roginski R, Schubert J.

Applied Spectroscopy 68(10):1108-1115.

Laila Kott, Jelena Petrovic, Dean Phelps, Robert Roginksi, Jared Schubert

[T7] A new approach to forced degradation studies using anhydrous conditions Elizabeth Hewitt, Laila Kott, Jun Wang, Nick Yankauskas, Chris Franklin

Pharmaceutical Technology and Pharmaceutical Technology Europe. 2014; Volume 38, Issue 3, pp. 64-70

Elizabeth Hewitt, Laila Kott, Jun Wang, Nick Yankauskas, Chris Franklin

Organic Chemistry [T8] Continuous-Flow Tubular Crystallization in Slugs Spontaneously Induced by Hydrodynamics Mo Jiang, Zhilong Zhu, Ernesto Jimenez, Charles D. Papageorgiou, Josh Waetzig, Andrew Hardy, Marianne

Langston, and Richard D. Braatz

Crystal Growth & Design, 2014, 14 (2), 851–860

Mo Jiang, Zhilong Zhu, Ernesto Jimenez, Charles D. Papageorgiou, Josh Waetzig, Andrew Hardy, Marianne

Langston, and Richard D. Braatz

[T9] Development of Large-Scale Synthesis using a Palladium-Catalyzed Cross-Coupling Reaction for an Isoquinolone Derivative as a Potent DPP-4 Inhibitor Misayo Sera, Makoto Yamashita, Yuujirou Ono, Takashi Tabata, Eigo Muto, Takashi Ouchi, Hiroyuki Tawada

Organic Process Research & Development, 18, 446, 2014

Misayo Sera, Makoto Yamashita, Yuujirou Ono, Takashi Tabata, Eigo Muto, Takashi Ouchi, Hiroyuki Tawada

瀬良 美佐代、山下 誠、小野 祐二朗、田畑 隆志、武藤 英吾、大内 卓、多和田 紘之

[T10] Part 2: Designation and Justification of API Starting Materials: Current Practices across Member Companies of the IQ Consortium Margaret M. Faul, Carl A. Busacca, Magnus C. Eriksson, Fred Hicks, William F. Kiesman, Maciej Smulkowski,

John D. Orr, Steven Pfeiffer

Org. Process Res. Dev., 2014, 18 (5), pp 594–600

Margaret M. Faul, Carl A. Busacca, Magnus C. Eriksson, Fred Hicks, William F. Kiesman, Maciej Smulkowski,

John D. Orr, Steven Pfeiffer

3

[T11] Synthesis of a stable triformylmethane synthon and its scalable application to 7-acylamino-3-formylquinoline syntheses Yasuhiro Sawai, Masahiro Mizuno, Tatsuya Ito, Mitsuhisa Yamano

Tetrahedron, 70, 2370, 2014

Yasuhiro Sawai, Masahiro Mizuno, Tatsuya Ito, Mitsuhisa Yamano

澤井 泰宏、水野 正博、伊藤 達也、山野 光久

[T12] Synthesis of a novel tricyclic 1,6,7,8-tetrahydro-2H-cyclopenta[b]furo[3,2-d]pyridine derivative, the 5-aza analog of ramelteon Yasutaka Hoashi, Takafumi Takai, Tatsuki Koike, Osamu Uchikawa

Tetrahedron Letters Volume 55, Issue 29, Pages 4014–4016 2014

帆足 保孝、高井 隆文、小池 竜樹、内川 治

[T13] Development of a Modeling-Based Strategy for the Safe and Effective Scale-up of Highly Energetic Hydrogenation Reactions Christopher W. Mitchell, Josiah D. Strawser, Alex Gottlieb, Michael H. Millonig, Frederick A. Hicks, Charles D.

Papageorgiou

Org. Process Res. Dev. 2014, 18, 1828−1835

Christopher W. Mitchell, Josiah D. Strawser, Alex Gottlieb, Michael H. Millonig, Frederick A. Hicks, Charles D.

Papageorgiou

[T14] Rapid access to diverse α-carbolines through sequential transition metal catalyzed amination and direct C-H arylation Masahiro Mineno, Misayo Sera, Tsuyoshi Ueda, Masahiro Mizuno, Mitsuhisa Yamano, Hideya Mizufune, Atsuhiko

Zanka

Tetrahedron, 70, 5550, 2014

Masahiro Mineno, Misayo Sera, Tsuyoshi Ueda, Masahiro Mizuno, Mitsuhisa Yamano, Hideya Mizufune, Atsuhiko

Zanka

峯野 雅博、瀬良 美佐代、上田 剛士、水野 正博、山野 光久、水船 秀哉、残華 敦彦

[T15] Process Intensification for the Continuous Flow Hydrogenation of Ethyl Nicotinate Takashi Ouchi, Claudio Battilocchio, Steven V. Ley

Org. Process Res. Dev. 2014, 18, 1560-1566.

Takashi Ouchi, Claudio Battilocchio, Steven V. Ley

大内 卓, Claudio Battilocchio, Steven V. Ley

[T16] Control of Crystal Size during Oiling Out Crystallization of an API

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Masahiro Takasuga, Hiroshi Ooshima

Crystal Growth & Design 14, 6006−6011, 2014

Masahiro Takasuga, Hiroshi Ooshima

高須賀 正博、大嶋 寛

[T17] Preparation of (2, 3-dihydrobenzofuran-3-yl)acetic acid via Rh-catalyzed asymmetric hydrogenation Masayuki Yamashita1), Nobuyuki Negoro2), Tsuneo Yasuma1), Toru Yamano3)

BullChemSocJpn2014_87_539

山下 真之、山野 徹、根来 伸行、安間 常雄 1) Chemical Development Laboratories, CMC Center, Takeda Pharmaceutical Company Limited, 2) Pharmaceutical

Research Division, Takeda Pharmaceutical Company Limited, 3) Environment & Safety Department, Takeda

Pharmaceutical Company Limited

Medicinal Chemistry [T18] Design, synthesis, and biological evaluation of a series of piperazine ureas as fatty acid amide hydrolase inhibitors Kono M1, Matsumoto T2, Imaeda T2, Kawamura T2, Fujimoto S2, Kosugi Y2, Odani T2, Shimizu Y2, Matsui H2,

Shimojo M2, Kori M3.

Bioorganic & Medicinal Chemistry 22 (2014) 1468–1478

髙野 光功、松本 孝浩、今枝 稔博、河村 透、藤本 真二、小杉 洋平、小谷 知之、清水 裕二、

松井 英起、下条 雅人、郡 正城

1Pharmaceutical Research Division, Takeda Pharmaceutical Company Ltd, 26-1, Muraokahigashi 2-Chome,

Fujisawa, Kanagawa 251-8555, Japan.

2Pharmaceutical Research Division, Takeda Pharmaceutical Company Ltd, 2

[T19] Discovery of a novel series of indoline carbamate and indolinylpyrimidine derivatives as potent GPR119 agonists Sato K1, Sugimoto H2, Rikimaru K2, Imoto H2, Kamaura M2, Negoro N2, Tsujihata Y2, Miyashita H2, Odani T2,

Murata T2.

Bioorganic & Medicinal Chemistry, Volume 22, Issue 5, Pages 1649-1666, 2014

佐藤 健二郎、杉本 浩通、力丸 健太郎、井元 広士、竃浦 政宏、根来 伸行、辻畑 善行、宮下

裕久、小谷 知之、村田 俊樹

[T20] A fragment-based approach to identifying S-adenosyl-l-methionine -competitive inhibitors of catechol O-methyl transferase (COMT). Lanier M, Ambrus G, Cole DC, Davenport R, Ellery J, Fosbeary R, Jennings AJ, Kadotani A, Kamada Y, Kamran R,

5

Matsumoto S, Mizukami A, Okubo S, Okada K, Saikatendu K, Walsh L, Wu H, Hixon MS.

J Med Chem. 2014 Jun 26;57(12):5459-63. doi: 10.1021/jm500475k. Epub 2014 Jun 4.

Lanier M, Ambrus G, Cole DC, Davenport R, Ellery J, Fosbeary R, Jennings AJ, Kadotani A, Kamada Y, Kamran R,

Matsumoto S, Mizukami A, Okubo S, Okada K, Saikatendu K, Walsh L, Wu H, Hixon MS.

[T21] Discovery of the First Potent and Orally Available Agonist of the Orphan G-Protein Coupled Receptor 52 Setoh M, Ishii N, Kono M, Miyanohana Y, Shiraishi E, Harasawa T, Ota H, Odani T, Kanzaki N, Aoyama K,

Hamada T, Kori M.

Journal of Medicinal Chemistry., 57, pp 5226–5237, 2014

瀬藤 正記、石井 直樹、高野 光功、宮野鼻 悠平、橋本 絵理、原澤 俊也、太田 浩之、小谷 知

之、神崎 直之、青山 和誠、濱田 輝基、郡 正城

[T22] Design, synthesis, and biological activities of 1-aryl-1,4-diazepan-2-one derivatives as novel triple reuptake inhibitors Honda E, Ishichi Y, Kimura E, Yoshikawa M, Kanzaki N, Nakagawa H, Terao Y, Suzuki A, Kawai T, Arakawa Y,

Ohta H, Terauchi J.

Bioorganic & Medicinal Chemistry Letters 24 (2014) 3898–3902

本多 栄治，石地 雄二，木村 英司，吉川 真人，神埼 直之，中川 秀行，寺尾 寧子，鈴木 敦

子，河合 隆幸，荒川 祐一，太田 浩之，寺内 淳

[T23] Discovery of 6-[5-(4-fluorophenyl)-3-methyl-pyrazol-4-yl]-benzoxazin-3-one derivatives as novel selective nonsteroidal mineralocorticoid receptor antagonists Hasui T1, Ohyabu N2, Ohra T2, Fuji K2, Sugimoto T2, Fujimoto J2, Asano K2, Oosawa M2, Shiotani S2, Nishigaki

N2, Kusumoto K2, Matsui H2, Mizukami A2, Habuka N2, Sogabe S2, Endo S2, Ono M2, Siedem CS3, Tang TP3,

Gauthier C3, De Meese LA3, Boyd SA3, Fukumoto S

Bioorganic & Medicinal Chemistry, 2014, 22, 5428-5445

蓮井 智章, 大藪 紀雄, 邑楽 泰一, 富士 晃嗣, 杉本 貴裕, 藤本 潤, 麻野 耕平, 大澤 壮登, 塩

谷 紗知子, 西垣 信裕, 楠本 啓司, 松井 英起, 水上 温司, 羽深 典之, 曽我部 智, 遠藤 聡史,

小野 みどり, Christopher S. Siedem, Tony P. Tang, Cassandra Gauthier, Lisa A. De Meese、Steven A. Boyd, 福

本 正司 1Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-higashi, 2-Chome,

Fujisawa, Kanagawa 251-8555, Japan. 2Pharmaceutical Research Division, Takeda Pharmaceutical Company Li 3Array BioPharma Inc., 3200 Walnut Street, Boulder, CO 80301, United States.

[T24] Thieno[2,3-d]pyrimidine-2-carboxamides bearing a carboxybenzene group at 5-position: highly potent, selective, and orally available MMP-13 inhibitors interacting with the S1″

6

binding site. Hiroshi Nara ⇑, Kenjiro Sato, Takako Naito, Hideyuki Mototani, Hideyuki Oki, Yoshio Yamamoto, Haruhiko Kuno, Takashi Santou, Naoyuki Kanzaki, Jun Terauchi, Osamu Uchikawa, Masakuni Kori Bioorg Med Chem. 2014 Oct 1;22(19):5487-505.

奈良 洋、佐藤 健二郎、内藤 貴子、本谷 英之、沖 英幸、山本 善雄、山東 尚、神崎 直之、

寺内 淳、郡 正城

[T25] Kiss1 Mutant Placentas Show Normal Structure and Function A.M. Herreboudt, V.R.L. Kyle, J. Lawrence, J. Doran. W.H. Colledge

Placenta, 2014, 36(1), 52-58

Herreboudt AM1, Kyle VR1, Lawrence J2, Doran J2, Colledge WH3. 1Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG,

United Kingdom. 2Takeda Cambridge, 418 Science Park, Milton Road, Cambridge CB4 0PZ, United Kingdom. 3Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge CB2 3EG,

United Kingdom.

[T26] Discovery of 1 ‑ [2-Fluoro-4-(1H ‑ pyrazol-1-yl)phenyl]-5-methoxy-3-(1-phenyl ‑ 1H ‑pyrazol-5-yl)pyridazin-4(1H)‑one (TAK-063), a Highly Potent, Selective, and Orally Active Phosphodiesterase 10A (PDE10A) Inhibitor Jun Kunitomo, Masato Yoshikawa, Makoto Fushimi, Akira Kawada, John F. Quinn, Hideyuki Oki, Hironori

Kokubo, Mitsuyo Kondo, Kosuke Nakashima, Naomi Kamiguchi, Kazunori Suzuki, Haruhide Kimura, Takahiko

Taniguchi

Journal of Medicinal Chemistry 2014, 57, 9627–9643

國友 潤、吉川 真人、伏見 真、河田 彰、John F. Quinn、沖 英幸、小久保 裕功、近藤 光代、中

島 康祐、上口 尚美、鈴木 一典、木村 温英、谷口 孝彦

[T27] Discovery of novel, highly potent, and selective quinazoline-2-carboxamide-based matrix metalloproteinase (MMP)-13 inhibitors without a zinc binding group using a structure-based design approach. Hiroshi Nara,* Kenjiro Sato, Takako Naito, Hideyuki Mototani, Hideyuki Oki, Yoshio Yamamoto, Haruhiko Kuno, Takashi Santou, Naoyuki Kanzaki, Jun Terauchi, Osamu Uchikawa, and Masakuni Kori J Med Chem. 2014 Nov 13;57(21):8886-902.

奈良 洋、佐藤 健二郎、内藤 貴子、本谷 英之、沖 英幸、山本 善雄、山東 尚、神崎 直之、

寺内 淳、郡 正城

7

[T28] Molecular Modeling, Design, Synthesis, and Biological Activity of 1H-Pyrrolo[2,3-c] pyridine-7-amine Derivatives as Potassium-Competitive Acid Blockers. Arikawa Y, Hasuoka A, Hirase K, Inatomi N, Sato F, Hori Y, Takagi T, Tarui N, Kawamoto M, Kajino M

Chem. Pharm. Bull. 62 (4) 336-342 (2014)

有川 泰由、蓮岡 淳、平瀨 慶造、稲富 信博、佐藤 文彦、堀 靖亘、髙木 輝文、樽井 直樹、

河本 眞紀子、梶野 正博

Biochemistry and Biotechnology [T29] Inhibition mechanism exploration of investigational drug TAK-441 as inhibitor against Vismodegib-resistant Smoothened mutant Ishii T, Shimizu Y, Nakashima K, Kondo S, Ogawa K, Sasaki S, Matsui H.

European Journal of Pharmacology 723 (2014) 305–313

石井 剛、清水 裕二、中島 康祐、近藤 滋、小川 和雅、佐々木 聡、松井 英起

[T30] Generating thermostabilized agonist-bound GPR40/FFAR1 using viruslike particles and a label-free binding assay Hirozane Y, Motoyaji T, Maru T, Okada K, Tarui N.

Molecular Membrane Biology, 2014; 31(5): 168–175

廣實 慶彦、元屋地 孝士、丸 喬光、岡田 健吾、樽井 直樹

[T31] High-resolution structure of the human GPR40 receptor bound to allosteric agonist TAK-875. Srivastava A1, Yano J1, Hirozane Y2, Kefala G3, Gruswitz F4, Snell G3, Lane W3, Ivetac A3, Aertgeerts K4, Nguyen

J4, Jennings A3, Okada K2.

Nature. 2014 Sep 4;513(7516):124-7. doi: 10.1038/nature13494. Epub 2014 Jul 20.

Srivastava A1, Yano J1, Hirozane Y2, Kefala G3, Gruswitz F4, Snell G3, Lane W3, Ivetac A3, Aertgeerts K4, Nguyen

J4, Jennings A3, Okada K2. 1[1] Department of Structural Biology and Core Sciences &Technology, Takeda California, 10410 Science Center

Drive, San Diego, California 92121, USA [2]. 2Biomolecular Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company L 3Department of Structural Biology and Core Sciences &Technology, Takeda California, 10410 Science Center

Drive, San Diego, California 92121, USA. 4[1] Department of Structural Biology and Core Sciences &Technology, Takeda California, 10410 Science Center

Drive, San Diego, California 92121, USA [2] Beryllium, Membrane Protein Sciences, 7869 NE Day Road West,

Bainbridge Island, Washington 98110, USA (F.G.); Dart Neuroscience, 12278 Scripps Summit Drive, San Diego,

California 92131, USA (K.A. and J.N.).

8

[T32] Cancer cell death induced by novel small molecules degrading the TACC3 protein via the ubiquitin–proteasome pathway Ohoka N, Nagai K, Hattori T, Okuhira K, Shibata N, Cho N, Naito M.

Cell Death and Disease (2014) 5, e1513; doi:10.1038/cddis.2014.471.

大岡 伸通、永井 克典、服部 隆行、奥平 桂一郎、柴田 識人、長 展生、内藤 幹彦

[T33] A simple and widely applicable hit validation strategy for protein-protein interaction inhibitors based on a quantitative ligand displacement assay. Sameshima T1, Miyahisa I2, Homma M1, Aikawa K1, Hixon MS3, Matsui J1.

Bioorg Med Chem Lett. 2014 Dec 15;24(24):5836-9

鮫島 知哉、宮久 郁夫、本間 実咲、合川 勝二、Mark S. Hixon、松井 純二 1Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-higashi 2-chome,

Fujisawa, Kanagawa 251-8555, Japan. 2Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1, Muraoka-higashi 2-chome,

Fujisawa, 3Enzymology and Biophysical Chemistry, Takeda California, Inc., 10410 Science Center Drive, San Diego, CA

92121, United States.

Immunology [T34] Expression of Mas-related gene X2 on mast cells is upregulated in the skin of patients with severe chronic urticaria. Kikukawa Y, Fujitani Y

J Allergy Clin Immunol. 134(3):622-633 (2014)

菊川 裕介 藤谷 靖志

Pharmacology [T35] Effects of a farnesoid X receptor antagonist on hepatic lipid metabolism in primates. Amano Y, Shimada M, Miura S, Adachi R, Tozawa R.

Eur J Pharmacol. 2014 Jan 15;723:108-15.

天野 雄一郎、島田 満之、三浦 正太郎、安達 竜太郎、兎澤 隆一

[T36] Suppression of the hypothalamic–pituitary–gonadal axis by TAK-385 (relugolix), a novel, investigational, orally active, small molecule gonadotropin-releasing hormone (GnRH) antagonist: Studies in human GnRH receptor knock-in mice Nakata D, Masaki T, Tanaka A, Yoshimatsu M, Akinaga Y, Asada M, Sasada R, Takeyama M, Miwa K, Watanabe T,

Kusaka M.

9

European Journal of Pharmacology, 723, 167-174 (2014)

中田 大介、正木 恒男、田中 晃、吉松 美恵、秋永 由美子、淺田 真理、佐々田 玲子、竹山 道

康、三輪 憲弘、渡邉 辰也、日下 雅美

[T37] Novel TRPM8 Antagonists Attenuates Cold Hypersensitivity after Peripheral Nerve Injury in Rats R. Patel, L. Gonçalves, R. Newman, F.L. Jiang, A. Goldby, J. Reeves, A. Hendrick, M. Teall, D. Hannah, S.

Almond, N. Brice, A.H. Dickenson

J Pharm and Exp Ther, Apr-14, 349(1), 47-55

R. Patel, L. Gonçalves, R. Newman, F.L. Jiang, A. Goldby, J. Reeves, A. Hendrick, M. Teall, D. Hannah, S.

Almond, N. Brice, A.H. Dickenson

[T38] Preclinical FLT-PET and FDG-PET imaging of tumor response to the multi-targeted Aurora B kinase inhibitor, TAK-901. Cullinane C1, Waldeck KL2, Binns D3, Bogatyreva E2, Bradley DP4, de Jong R5, McArthur GA6, Hicks RJ7.

Nucl Med Biol. 2014 Feb;41(2):148-54. doi: 10.1016/j.nucmedbio.2013.11.001. Epub 2013 Nov 15.

Cullinane C1, Waldeck KL2, Binns D3, Bogatyreva E2, Bradley DP4, de Jong R5, McArthur GA6, Hicks RJ7. 1Division of Cancer Research, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia; Sir Peter

MacCallum Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia. 2Division of Cancer Research, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia. 3Centre for Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia. 4Millennium Pharmaceuticals, Cambridge, MA. 5Takeda California, San Diego, CA. 6Division of Cancer Research, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia; Division of

Cancer Medicine, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia; Department of Medicine,

St Vincent's Hospital, The University of Melbourne, Parkville, Victoria, Australia; Sir Peter MacCallum

Department of Oncology, The University of Melbourne, Parkville, Victoria, Australia. 7Division of Cancer Research, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia; Centre for

Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, Victoria, Australia; Department of Medicine, St

Vincent's Hospital, The University of Melbourne, Parkville, Victoria, Australia; Sir Peter MacCallum Department

of Oncology, The University of Melbourne, Parkville, Victoria, Australia.

[T39] Activation of peripheral KCNQ channels attenuates inflammatory pain Hayashi H, Iwata M, Tsuchimori N, Matsumoto T.

Molecular Pain 2014, 10:15

林 宏樹、岩田 雅史、土森 登、松本 辰美

[T40] Identification of a novel GPR81-selective agonist that suppresses

10

lipolysis in mice without cutaneous flushing Sakurai T1, Davenport R2, Stafford S2, Grosse J2, Ogawa K3, Cameron J2, Parton L2, Sykes A2, Mack S2, Bousba S2,

Parmar A2, Harrison D2, Dickson L2, Leveridge M2, Matsui J3, Barnes M2.

European Journal of Pharmacology 727 (2014) 1–7

桜井 卓、小川 和雅、松井 純二 1Biomolecular Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company

Limited, 26-1, Muraoka-higashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan. 2Takeda Cambridge, 418 Cambridge Science Park, CB4 OPA Cambridge, GB, United Kingdom. 3Biomolecular Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company

Limited, 26-1, Muraoka-higashi 2-chome, Fujisawa, Kanagawa 251-8555, Japan.

[T41] The MCH1 receptor, an anti-obesity target, is allosterically inhibited by 8-methylquinoline derivatives possessing subnanomolar binding and long residence times T Sakurai, K Ogawa, Y Ishihara, S Kasai and M Nakayama

British Journal of Pharmacology, (2014) 171 1287–1298

桜井 卓、小川 和雅、石原 雄二、河西 静夫、中山 政治

[T42] Antidyslipidemic effects of a farnesoid X receptor antagonist in primates. Amano Y, Shimada M, Miura S, Adachi R, Tozawa R.

Life Sci. 2014 Jun 13;106(1-2):25-31.

天野 雄一郎、島田 満之、三浦 正太郎、安達 竜太郎、兎澤 隆一

[T43] Pharmacological characterization of M-II, the major human metabolite of ramelteon. Nishiyama K, Nishikawa H, Kato K, Miyamoto M, Tsukamoto T, Hirai K.

Pharmacology. 93(3-4):197-201. 2014

西山 啓次、西川 久夫、加藤 浩紀、宮本 政臣、塚本 徹哉、平井 圭介

[T44] Combinational effects of farnesoid X receptor antagonist and statin on plasma lipid levels and low-density lipoprotein clearance in guinea pigs. Amano Y, Ishikawa E, Shinozawa E, Shimada M, Miura S, Adachi R, Tozawa R.

Life Sci. 2014 Jul 11;108(1):7-12.

天野 雄一郎、石川 英一郎、篠澤 恵巳子、島田 満之、三浦 正太郎、安達 竜太郎、兎澤 隆一

[T45] Pharmacologic profiles of investigational kisspeptin/metastin analogues, TAK-448 and TAK-683, in adult male rats in comparison to the GnRH analogue leuprolide. Matsui H1, Masaki T2, Akinaga Y2, Kiba A2, Takatsu Y2, Nakata D2, Tanaka A2, Ban J3, Matsumoto S2, Kumano S2,

Suzuki A2, Ikeda Y3, Yamaguchi M2, Watanabe T2, Ohtaki T2, Kusaka M3.

Eur J Pharmacol 735C:77-85

11

松井 久典、正木 恒夫、秋永 由美子、木場 篤司、中田 大介、田中 晃、伴 淳子、松本 真一、

熊野 聡、鈴木 敦子、池田 幸弘、山口 昌史、渡辺 辰也、大瀧 徹也、日下 雅美 1Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 26-1 Muraoka-Higashi 2-chome,

Fujisawa, Kanagawa 251-8555, Japan. 2Pharmaceutical Research Division, Takeda Pharmaceutical Company Li 3CMC Center, Takeda Pharmaceutical Company Limited, 17-85 Jusohonmachi 2-chome, Yodogawa-ku, Osaka

532-8686, Japan.

[T46] The melatonin agonist ramelteon induces duration-dependent clock gene expression through cAMP signaling in pancreatic INS-1 β-cells. Nishiyama K, Hirai K.

PLoS One. 9(7):e102073. 2014.

西山 啓次、平井 圭介

[T47] Discovery and development of a selective GPR40/FFAR1 agonist, fasiglifam, for treatment of type 2 diabetes mellitus Tsujihata Y.

Nihon Yakurigaku Zasshi., 144(2):59-63, 2014

辻畑 善行

[T48] Characteristics of TRK-130 (Naltalimide), a Novel Opioid Ligand, as a New Terapeutic Agent for Overactive Bladder Okanishi S, Hashimoto T.

J Pharmacol Exp Ther 350:543-551, September 2014

橋本 忠俊、岡西 聡

[T49] Effects and therapeutic potentials of kisspeptin analogs: regulation of the hypothalamic-pituitary-gonadal axis. Matsui H, Asami T.

Neuroendocrinology 99:49-60 (2014)

松井 久典、浅見 泰司

[T50] Pharmacological Characterization of a Highly Selective and Potent Partial Agonist of the MT 2 Melatonin Receptor Sakurai T, Koike T, Nakayama M.

Pharmacology, 93:244–252, 2014

桜井 卓、小池 竜樹、中山 政治

12

Basic Biology and Physiology [T51] Nicotine induces dendritic spine remodeling in cultured hippocampal neurons Oda A, Yamagata K, Nakagomi S, Uejima H, Wiriyasermkul P, Ohgaki R, Nagamori S, Kanai Y, Tanaka H.

Journal of Neurochemistry, Volume 128, Issue 2, pages 246–255, January 2014

小田 明, 山形 要人, 中込 咲綾, 上島 宗之, 大垣 隆一, 永森 収志, 金井 好克, 田中 秀和

[T52] Anatomical transcriptome of G protein-coupled receptors leads to the identification of a novel therapeutic candidate GPR52 for psychiatric disorders Komatsu H1, Maruyama M2, Yao S3, Shinohara T4, Sakuma K2, Imaichi S4, Chikatsu T2, Kuniyeda K5, Siu FK6,

Peng LS6, Zhuo K7, Mun LS7, Han TM7, Matsumoto Y3, Hashimoto T8, Miyajima N3, Itoh Y9, Ogi K4, Habata Y2,

Mori M2.

PLoS One. February 28, 2014 | Volume 9 | Issue 2 | e90134

小松 秀俊,丸山 穣, 八尾 修平, 篠原 徳之, 佐久間 健介, 今市 祥子, 千勝 智子, 國枝 香南子,

Foo Kok Siu, Lam Sock Peng, Katherine Zhuo, Lay Sock Mun, Tan Min Han, 松本 芳男, 橋本 忠俊, 宮嶋

伸行, 伊藤 康明, 大儀 和宏, 羽畑 祐吾, 森 正明 1Central Nervous System Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical

Company Limited, Fujisawa, Kanagawa, Japan. 2Cardiovascular and Metabolic Drug Discovery Unit, Pharmaceutical Research Division, Takeda Pharmaceutical

Com 3Biomolecular Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company

Limited, Fujisawa, Kanagawa, Japan. 4Advanced Science Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company

Limited, Fujisawa, Kanagawa, Japan. 5Extra Value Generation and General Medicine Drug Discovery Unit, Pharmaceutical Research Division, Takeda

Pharmaceutical Company Limited, Fujisawa, Kanagawa, Japan. 6TSP CNS Phenotyping, Takeda Pharmaceutical Company Limited, Singapore. 7TSP Transgenic pipeline, Takeda Pharmaceutical Company Limited, Singapore. 8Research Administration Department, Pharmaceutical Research Division, Takeda Pharmaceutical Company

Limited, Fujisawa, Kanagawa, Japan. 9Pharmaceutical Marketing Division, Takeda Pharmaceutical Company Limited, Fujisawa, Kanagawa, Japan.

[T53] Resolution Mediator Chemerin15 Reprogrammes the Wound Microenvironment to Promote Repair and Reduce Scarring J. L. Cash, M.D. Bass, J. Campbell, M. Barnes, P. Kubes, P. Martin

Current Biology, 2014, 24

J. L. Cash, M.D. Bass, J. Campbell, M. Barnes, P. Kubes, P. Martin

13

[T54] Early-onset cognitive deficits and axonal transport dysfunction in P301S mutant tau transgenic mice Onishi T1, Matsumoto Y2, Hattori M1, Obayashi Y1, Nakamura K1, Yano T2, Horiguchi T2, Iwashita H3.

Neuroscience Research 80 (2014) 76–85

大西 智裕 松本 芳男 服部 正彦 大林 由佳 中村 希巳江 矢野 隆 堀口 隆司 岩下 弘

樹 1CNS Drug Discovery Unit, Takeda Pharmaceutical Company, Limited, Japan. 2Biomolecular Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company,

Limited, Japan. 3CNS Drug Discovery Unit, Takeda Pharmaceutical Company, Limited

[T55] HER2 and HER3 cooperatively regulate cancer cell growth and determine sensitivity to the novel investigational EGFR/HER2 kinase inhibitor TAK-285 Takagi S, Banno H, Hayashi A, Tamura T, Ishikawa T, Ohta Y.

Oncoscience, Volume 1, Issue 3, page 196-204, 2014

髙木 慎二、坂野 浩、林 哲、田村 寿哉、石川 智康、大田 義一

[T56] Ovarian and hormonal responses to follicular phase administration of investigational metastin/kisspeptin analog, TAK-683, in goats. Goto Y, Endo N, Nagai K, Ohkura S, Wakabayashi Y, Tanaka A, Matsui H, Kusaka M, Okamura H, Tanaka T.

Reprod Domest Anim. 2014 Apr;49(2):338-42.

後藤 侑, 遠藤 なつ美、永井 淸亮、大蔵 聡, 若林 嘉浩, 田中 晃、松井 久典、日下 雅美, 岡

村 裕昭、田中 知己

[T57] Brain Testosterone Deficiency Leads to Down-Regulation of Mitochondrial Gene Expression in Rat Hippocampus Accompanied by a Decline in Peroxisome Proliferator-Activated Receptor-γ Coactivator 1α Expression Hioki T, Suzuki S, Morimoto M, Masaki T, Tozawa R, Morita S, Horiguchi T.

Journal of Molecular Neuroscience 52 (4) 531-537, 2014

日置 剛司、鈴木 俊也、森本 恵、正木 恒男、兎澤 隆一、森田 滋、堀口 隆司

[T58] Involvement of ER Stress in Dysmyelination of Pelizaeus-Merzbacher Disease with PLP1 Missense Mutations Shown by iPSC-Derived Oligodendrocytes Numasawa-Kuroiwa Y1, Okada Y2, Shibata S3, Kishi N3, Akamatsu W3, Shoji M4, Nakanishi A4, Oyama M5, Osaka

H6, Inoue K7, Takahashi K8, Yamanaka S8, Kosaki K9, Takahashi T10, Okano H3.

Stem Cell Reports Vol. 2, 648–661, 2014

沼澤 祐子、岡田 洋平、芝田 晋介、岸 憲幸、赤松 和土、庄司 昌伸、中西 淳、大山 学、小

坂 仁、井上 健、高橋 和利、山中 伸弥、小崎 健次郎、高橋 孝雄、岡野 栄之

14

1Department of Physiology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582,

Japan ; Department of Pediatrics, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo

160-8582, Japan. 2Department of Physiology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582,

Japan ; Department of Neurology, School of Medicine, Aichi Medical University, 1-1 Yazako Karimata, Nagakute,

Aichi 480-1195, Japan. 3Department of Physiology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582,

Japan. 4Advanced Science Research Laboratories, Takeda Pharmaceutical Company Limited, 26-1 Muraoka-Higashi

2-Chome, Fujisawa, Kanagawa 251-8555, Japan.

5Department of Dermatology, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo

160-8582, Japan. 6Department of Pediatrics, Jichi Medical School, 3311-1 Yakushiji, Shimotsuke-shi, Tochigi 329-0498, Japan. 7Department of Mental Retardation and Birth Defect Research, National Institute of Neuroscience, National Center

of Neurology and Psychiatry, 4-1-1 Ogawahigashi-machi, Kodaira-shi, Tokyo 187-8551, Japan. 8Center for Induced Pluripotent Stem Cell Research and Application, Graduate School of Medicine, Institute for

Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan. 9Center for Medical Genetics, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo

160-8582, Japan. 10Department of Pediatrics, School of Medicine, Keio University, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582,

Japan.

[T59] JARID1B is a Luminal Lineage-Driving Oncogene in Breast Cancer Yamamoto S1, Wu Z2, Russnes HG3, Takagi S1, Peluffo G1, Vaske C4, Zhao X5, Moen Vollan HK6, Maruyama R7,

Ekram MB1, Sun H8, Kim JH9, Carver K1, Zucca M10, Feng J11, Almendro V1, Bessarabova M12, Rueda OM13,

Nikolsky Y12, Caldas C13, Liu XS14, Polyak K15.

Cancer Cell, Volume 25, Issue 6, pages 762-777, 2014

山本 昌司、髙木 慎二、丸山 玲緒 1Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Functional

Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham

and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA

02115, USA. 2Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA;

Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard School

of Public Health, Boston, MA 02115, USA. 3Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Functional

Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham

and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA

15

02115, USA; Oslo University Hospital, Radiumhospitalet, Oslo 0310, Norway. 4Five3 Genomics, Santa Cruz, CA 95060, USA. 5Stanford Center for Cancer Systems Biology, Department of Radiology, Stanford University School of Medicine,

Stanford, CA 94305, USA. 6Oslo University Hospital, Radiumhospitalet, Oslo 0310, Norway. 7Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Functional

Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham

and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA

02115, USA; School of Medicine, Sapporo Medical University, Sapporo 060-8556, Japan. 8Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of

Bioinformatics, School of Life Science and Technology, Tongji University, Shanghai 200092, China. 9Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Functional

Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham

and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA

02115, USA; Department of Internal Medicine, Seoul National University College of Medicine, Seoul 110-799,

Korea. 10Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Functional

Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA; San Raffaele University, 20132 Milan,

Italy. 11Department of Bioinformatics, School of Life Science and Technology, Tongji University, Shanghai 200092,

China. 12Thomson Reuters Healthcare & Science, Encinitas, CA 92024, USA. 13Cancer Research UK, Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK. 14Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA;

Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard School

of Public Health, Boston, MA 02115, USA; Broad Institute, Cambridge, MA 02141, USA. 15Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Center for Functional

Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Medicine, Brigham

and Women's Hospital, Boston, MA 02115, USA; Department of Medicine, Harvard Medical School, Boston, MA

02115, USA; Broad Institute, Cambridge, MA 02141, USA; Harvard Stem Cell Institute, Cambridge, MA 02138,

USA.

[T60] Macrophage-inducible C-type lectin underlies obesity-induced adipose tissue fibrosis Tanaka M1, Ikeda K1, Suganami T2, Komiya C1, Ochi K1, Shirakawa I3, Hamaguchi M1, Nishimura S4, Manabe I5,

Matsuda T6, Kimura K7, Inoue H7, Inagaki Y8, Aoe S9, Yamasaki S10, Ogawa Y1.

NATURE COMMUNICATIONS, 5, 4982, 1, 2014

田中 都 , 池田 賢司 , 菅波 孝祥 , 小宮 力 , 越智 梢 , 白川 伊吹 , 濱口 美穂 , 西村 智 ,

真鍋 一郎, 松田 貴久, 木村 久美, 井上 啓, 稲垣 豊, 青江 誠一郎, 山崎 晶, 小川 佳宏

16

1Department of Molecular Endocrinology and Metabolism, Graduate School of Medical and Dental Sciences,

Tokyo Medical and Dental University, Tokyo 113-8510, Japan. 2[1] Department of Organ Network and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo

Medical and Dental University, Tokyo 113-8510, Japan [2] Japan Science and Technology Agency, PRESTO,

Tokyo, Japan. 3Department of Organ Network and Metabolism, Graduate School of Medical and Dental Sciences, Tokyo Medical

and Dental University, Tokyo 113-8510, Japan. 4[1] Department of Cardiovascular Medicine, The University of Tokyo, Tokyo 113-8655, Japan [2] Translational

Systems Biology and Medicine Initiative, The University of Tokyo, Tokyo 113-8655, Japan [3] Jichi Medical

University, Tochigi 329-0498, Japan. 5Department of Cardiovascular Medicine, The University of Tokyo, Tokyo 113-8655, Japan. 6Pharmaceutical Research Division, Takeda Pharmaceutical Company, Fujisawa 251-8555, Japan. 7Department of Physiology and Metabolism, Brain/Liver Interface Medicine Research Center, Kanazawa

University, Kanazawa 920-8641, Japan. 8Department of Regenerative Medicine, Center for Matrix Biology and Medicine, Tokai University School of

Medicine, Isehara 259-1193, Japan. 9Department of Home Economics, Otsuma Women's University, Tokyo 102-8357, Japan. 10Division of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582,

Japan.

[T61] The Anti-hyperalgesic Effects of Novel TRPM8 Agonists in Neuropathic Rats: A Comparison with Menthol R. Patel, L. Gonçalves, M. Leveridge, S. Mack, A. Hendrick, N. Brice, A.H. Dickenson

Pain, Oct-14, 155(10), 2097-2107

R. Patel, L. Gonçalves, M. Leveridge, S. Mack, A. Hendrick, N. Brice, A.H. Dickenson

[T62] The Effects of Chronic Subcutaneous Administration of an Investigational Kisspeptin Analog, TAK-683, on Gonadotropin-Releasing Hormone Pulse Generator Activity in Goats Yamamura T, Wakabayashi Y, Sakamoto K, Matsui H, Kusaka M, Tanaka T, Ohkura S, Okamura H.

Neuroendocrinology 2014;100:250-264

山村 崇、若林 嘉浩、坂本 光平、松井 久典、日下 雅美, 田中 知己、大蔵 聡, 岡村 裕昭

Pharmacokinetics and Drug Metabolism [T63] Risk assessment of drug-drug interactions using hepatocytes suspended in serum during the drug discovery process Kosugi Y, Hirabayashi H, Igari T, Fujioka Y, Okuda T, Moriwaki T.

Xenobiotica. 2014 Apr;44(4):336-44

17

小杉 洋平、平林 英樹、猪狩 朋子、藤岡 泰、奥田 照明、森脇 俊哉

[T64] Main Metabolic Pathways of TAK-802, a Novel Drug Candidate for Voiding Dysfunction, in Humans: The Involvement of Carbonyl Reduction by 11β-hydroxysteroid Dehydrogenase 1. Nishihara M, Takahashi J, Kondo T, Mouri K, Asahi S.

Drug Research 2014;64(9):476-84.

西原 光洋、高橋 順三、近藤 孝浩、毛利 恒次、朝日 知

[T65] Retrospective Data Analysis and Proposal of a Practical Acceptance Criterion for Inter-laboratory Cross-validation of Bioanalytical Methods Using Liquid Chromatography /Tandem Mass Spectrometry Yoneyama T, Kudo T, Jinno F, Schmidt ER, Kondo T.

The AAPS Journal, Vol. 16, Issue 6, 1226-1236, 2014

米山 智城、工藤 喬、神野 文宏、Eric R. Schmidt、近藤孝浩

[T66] Clarification of P-glycoprotein inhibition-related drug–drug interaction risks based on a literature search of the clinical information Umeyama Y, Fujioka Y, Okuda T

Xenobiotica 44(12): 1135–1144, 2014

梅山 夕香里、藤岡 泰、奥田 照明

[T67] What is the definitive role of DMPK research for successful drug discovery and development? Until now and in the future Hirabayashi H

Drug Metabolism and Pharmacokinetics, Volume 29 357-359, (2014)

平林 英樹

Drug Safety Evaluation [T68] Common nature in the effects of thalidomide on embryo-fetal development in Kbl:JW and Kbl:NZW rabbits Kawamura Y, Shirotsuka Y, Awatsuji H, Matsumoto K, Sato K.

Congenital Anomalies 2014; 54, 41–53

河村 佳徳、城塚 康毅、粟辻 啓文、松本 清、佐藤 恵一朗

[T69] Effects of thalidomide on Fgf8, Bmp4 and Hoxa11 expression in the limb bud in Kbl:JW rabbit embryos Kawamura Y, Yamashita T, Yamauchi T, Matsumoto K, Sato K.

18

Congenital Anomalies 2014; 54, 54–62

河村 佳徳、山下 輝芳、山内 俊明、松本 清、佐藤 恵一朗

[T70] Historical control data on developmental toxicity studies in rodents Ema M, Endoh K, Fukushima R, Fujii S, Hara H, Hirata-Koizumi M, Hirose A, Hojo H, Horimoto M, Hoshino N,

Hosokawa Y, Imai Y, Inada H, Inawaka K, Itoh K, Katsumata Y, Izumi H, Kato H, Maeda M, Matsumoto K,

Matsuo S, Matsuoka T, Matsuura I, Mineshima H, Miwa Y, Nakano N, Naya M, Noyori H, Ohta T, Oku H, Ono A,

Shimizu T, Shimomura K, Takakura I, Tanaka R, Tateishi T, Tominaga Y, Uesugi T, Urakawa C, Yabe K, Yamashita

A, Yamauchi T, Yokoi R.

Congenital Anomalies, Volume 54, lsssue3, pages 150-161, August 2014

山内 俊明、松本 清、遠藤 克己、福島 亮、藤井 咲子、原 洋明、平田 睦子、広瀬 明彦、北

條 仁、堀本 政夫、星野 信人、細川 義典、今井 ゆかり、稲田 拓、稲若 邦文、伊藤 圭一、

和泉 宏幸、勝亦 芳裕、立石 大志、加藤 寛人、前田 麻希、松尾 成喜、松浦 郁夫、峯島 浩、

三輪 洋司、宮田 英典、中野 奈央、納屋 聖人、則武 健一、野寄 広子、大田 泰史、奥 春孝、

小野 敦、清水 達也、下村 和裕、高倉 郁朗、田中 亮太、富永 優子、上杉 透、浦川千 鶴、

矢部 薫、山下 晃人、横井 亮平、江馬 眞

Information Science [T71] Prediction of Ligand Binding Affinity by the Combination of Replica-Exchange Method and Double-Decoupling Method. Okamoto Y, Kokubo H, Tanaka T.

J. Chem. Theory Comput. 10, 3563-3569 (2014).

岡本 祐幸（名古屋大）、小久保 裕功（化研）、田中 稔祐（化研）

Technology Development [T72] Preparative two-dimensional liquid chromatography/mass spectrometry for the purification of complex pharmaceutical samples. Zhang Y, Zeng L, Pham C, Xu R.

J Chromatogr A. 2014 Jan 10;1324:86-95. doi: 10.1016/j.chroma.2013.11.022. Epub 2013 Nov 25.

Zhang Y, Zeng L, Pham C, Xu R.

19

Originals in Japanese Analytical Chemistry [T73] 粉末 X 線回折およびラマン分光法を用いた製剤中の結晶多形定量法の開発 垣尾 智子、廣島 高志、池田 幸弘

製剤機械技術学会誌 23、140-146 (2014)

Development of quantitative analysis for polymorph of drug substances in pharmaceutical oral dosage forms by

XRPD and raman spectroscopy

Tomoko Kakio, Takashi Hiroshima, Yukihiro Ikeda

Analytical Development Laboratories, CMC Center

Medicinal Chemistry [T74] 糖尿病治療薬を指向した GPR40/FFAR1 作動薬 Fasiglifam (TAK-875) の創製 根来 伸行、佐々木 忍、安間 常雄、武内 浩二、百瀬 祐

MEDCHEM NEWS

Discovery of Fasiglifam (TAK-875): A potent, selectice, and orally available GPR40/FFAR1 agonist for the

treatment of type 2 diabetes.

Nobuyuki Negoro, Shinobu Sasaki, Tsuneo Yasuma*, Koji Takeuchi, Yu Momose

MEDCHEM NEWS, 27-34, 24(2), 2014

Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited.

*CMC Center, Takeda Pharmaceutical Company Limited.

Pharmacology [T75] 自己免疫疾患における Toll-like receptor 4 の役割 北本 直美、山嵜 将司

日本薬理学雑誌、vol. 144、p167、2014

Role of Toll-like receptor 4 in autoimmune diseases

Naomi Kitamoto, Masashi Yamasaki

Folia Pharmacol. Jpn. vol. 144, p167, 2014

Inflammation drug discovery unit

[T76] アンドロゲン合成阻害薬（17,20-リアーゼ阻害薬） 原 隆人、山岡 万寿夫、日下 雅美

20

日本臨床 72 巻 増刊号２ （2014 年 2 月 20 日発行） p161-164 最新がん薬物療法学 -がん薬物療法の

最新知見-

Androgen synthesis inhibitors (17,20-lyase inhibitors)

Takahito Hara, Masuo Yamaoka, Masami Kusaka

Nippon Rinsho 72, p161-164, extra edition2, Feb 20, 2014 Innovation for medical treatment of cancer

Takahito Hara (Onco DDU), Masuo Yamaoka (Onco DDU), Masami Kusaka (Strategic CMC Planning, CMC

Center )

21

Author Index

[A]

A. Fisher

T1 A. Goldby

T37

A. Hendrick

T37, T61 A.H. Dickenson

T37, T25

A.M. Herreboudt

T25 Adachi R (安達 竜太郎) T35, T42, T44 Aertgeerts K

T31

Aikawa K (合川 勝二) T33 Akamatsu W (赤松 和土) T58 Akinaga Y (秋永 由美子) T36, T45 Alex Gottlieb

T13

Almendro V

T59 Amano Y (天野 雄一郎) T35, T42, T44 Ambrus G

T20

Andrew Hardy

T8 Aoe S (青江 誠一郎) T60 Aoyama K (青山 和誠) T21 Arakawa Y (荒川 祐一) T22 Arikawa Y (有川 泰由) T28 Asada M (淺田 真理) T36 Asahi S (朝日 知) T64 Asami T (浅見 泰司) T49 Asano K (麻野 耕平) T23 Awatsuji H (粟辻 啓文) T68

[B]

Ban J (伴 淳子) T45 Banno H (坂野 浩) T55 Barnes M

T40

Bessarabova M

T59 Binns D

T38

Bogatyreva E

T38 Bousba S

T40

22

Boyd SA

T23 Bradley DP

T38

[C]

C. M. McLuckey

T1 Caldas C

T59

Cameron J

T40 Carl A. Busacca

T10

Carver K

T59 Charles D. Papageorgiou

T8, T13

Chikatsu T (千勝 智子) T52 Cho N (長 展生) T32 Chris Franklin

T7

Christopher W. Mitchell

T13 Claudio Battilocchio

T15

Cole DC

T20 Cullinane C

T38

[D]

D. Hannah

T37 Davenport R

T20, T40

de Jong R

T38 De Meese LA

T23

Dean Phelps

T6 Dickson L

T40

[E]

Ekram MB

T59 Elizabeth Hewitt

T2, T7

Ellery J

T20 Ema M (松本 清) T70 Endo N (遠藤 なつ美) T56 Endo S (遠藤 聡史) T23 Endoh K (遠藤 克己) T70 Ernesto Jimenez

T8

[F]

F.L. Jiang

T37

23

Feng J

T59 Fisher CM

T4

Foo Kok Siu

T52 Fosbeary R

T20

Fred Hicks

T10 Frederick A. Hicks

T13

Fuji K (富士 晃嗣) T23 Fujii S (藤井 咲子) T70 Fujimoto J (藤本 潤) T23 Fujimoto S (藤本 真二) T18 Fujimura Morihiro

T48

Fujioka Y (藤岡 泰) T63, T66 Fujisawa D

T34

Fujitani Y (藤谷 靖志) T34 Fukumoto S (福本 正司) T23 Fukushima R (福島 亮) T70 Fushimi Makoto (伏見 真) T26

[G]

Gauthier C

T23 Goto Y (後藤 侑) T56 Grosse J

T40

Gruswitz F

T31

[H]

Habata Y (羽畑 祐吾) T52 Habuka N (羽深 典之) T23 Hamada T (濱田 輝基) T21 Hamaguchi M (濱口 美穂) T60 Hara H (原 洋明) T70 Hara Takahito (原 隆人) T76 Harasawa T (原澤 俊也) T21 Harrison D

T40

Hashimoto Tadatoshi (橋本 忠俊) T48, T52 Hasui T (蓮井 智章) T23 Hasuoka A (蓮岡 淳) T28 Hattori M (服部 正彦) T54 Hattori T (服部 隆行) T32

24

Hayama K

T34 Hayashi A (林 哲) T55 Hayashi H (林 宏樹) T39 Hicks RJ

T38

Hioki T (日置 剛司) T57 Hirabayashi H (平林 英樹) T63, T67 Hirai K (平井 圭介) T43, T46 Hirakata Mikito

T48

Hirase K (平瀨 慶造) T28 Hirata-Koizumi M (平田 睦子) T70 Hirose A (広瀬 明彦) T70 Hiroshima Takashi (廣島 高志) T73 Hirozane Y (廣實 慶彦) T30, T31 Hixon MS.

T20, T33

Hoashi Yasutaka (帆足 保孝) T12 Hojo H (北條 仁) T70 Homma M (本間 実咲) T33 Honda E (本多 栄治) T22 Hori Y (堀 靖亘) T28 Horiguchi T (堀口 隆司) T54, T57 Horimoto M (堀本 政夫) T70 Hoshino N (星野 信人) T70 Hosokawa Y (細川 義典) T70

[I]

Igari T (猪狩 朋子) T63 Ikeda K (池田 賢司) T60 Ikeda Yukihiro (池田 幸弘) T3, T5, T45, T73 Imaeda T (今枝 稔博) T18 Imai Y (今井 ゆかり) T70 Imaichi S (今市 祥子) T52 Imoto H (井元 広士) T19 Inada H (稲田 拓) T70 Inagaki Y (稲垣 豊) T60 Inatomi N (稲富 信博) T28 Inawaka K (稲若 邦文) T70 Inoue H (井上 啓) T60 Inoue K (井上 健) T58

25

Ishichi Y (石地 雄二) T22 Ishihara Y (石原 雄二) T41 Ishii N (石井 直樹) T21 Ishii T (石井 剛) T29 Ishikawa E (石川 英一郎) T44 Ishikawa T (石川 智康) T55 Ito Tatsuya (伊藤 達也) T11 Itoh K (伊藤 圭一) T70 Itoh Y (伊藤 康明) T52 Ivetac A

T31

Iwashita H (岩下 弘樹) T54 Iwata M (岩田 雅史) T39 Iwata, Kentaro (岩田 健太郎) T5 Izumi H (勝亦 芳裕) T70 Izumimoto Naoki

T48

[J]

J. Campbell

T53

J. Doran

T25 J. L. Cash

T53

J. Lawrence

T25 J. Reeves

T37

Jared Schubert

T6 Jelena Petrovic

T6

Jennings A

T31 Jennings AJ

T20

Jinno F (神野 文宏) T65 John D. Orr

T10

John F. Quinn

T26 Josh Waetzig

T8

Josiah D. Strawser

T13 Jun Wang

T2, T7

[K]

Kadotani A

T20

Kajino M (梶野 正博) T28 Kakio Tomoko (垣尾 智子) T73 Kamada Y

T20

26

Kamaura M (竃浦 政宏) T19 Kamiguchi Naomi (上口 尚美) T26 Kamran R

T20

Kanai Y (金井 好克) T51 Kanie Sayoko

T48

Kanzaki N (神崎 直之) T21, T22, T24, T27 Karashima, Masatoshi (辛島 正俊) T3 Kasai S (河西 静夫) T41 Kashiwakura J

T34

Katherine Zhuo

T52 Kato H (立石 大志) T70 Kato K (加藤 浩紀) T43 Katsumata Y (和泉 宏幸) T70 Kawada Akira (河田 彰) T26 Kawai Koji

T48

Kawai T (河合 隆幸) T22 Kawamoto M (河本 眞紀子) T28 Kawamura T (河村 透) T18 Kawamura Y (河村 佳徳) T68, T69 Kefala G

T31

Kharlamova

T1, T4 Kiba A (木場 篤司) T45 Kikukawa Y (菊川 裕介) T34 Kim JH

T59

Kimoto Kouya (木本 香哉) T3 Kimura E (木村 英司) T22 Kimura Haruhide (木村 温英) T26 Kimura K (木村 久美) T60 Kishi N (岸 憲幸) T58 Kita H

T34

Kitamoto Naomi (北本 直美) T75 Kobayashi Ryosuke

T48

Koike Tatsuki (小池 竜樹) T12, T50 Kojima Takashi (小嶌 隆史) T3, T5 Kokubo Hironori (小久保 裕功) T26, T71 Komagata Toshikazu

T48

Komatsu H (小松 秀俊) T52 Komiya C (小宮 力) T60

27

Kondo Mitsuyo (近藤 光代) T26 Kondo S (近藤 滋) T29 Kondo T (近藤 孝浩) T64, T65 Kono M (髙野 光功) T18, T21 Kori M (郡 正城) T18, T21, T24, T27 Kosaki K (小崎 健次郎) T58 Kosugi Y (小杉 洋平) T18, T63 Kudo T (工藤 喬) T65 Kumano S (熊野 聡) T45 Kunitomo Jun (國友 潤) T26 Kuniyeda K (國枝 香南子) T52 Kuno H

T24, T27

Kuroda K

T34 Kusaka Masami (日下 雅美) T36, T45, T56, T62, T76 Kusumoto K (楠本 啓司) T23

[L]

L. Gonçalves

T37, T61

Laila Kott

T6, T7 Lam Sock Peng

T52

Lane W

T31 Lanier M1

T20

Lay Sock Mun

T52 Leveridge M

T40

Liu XS

T59

[M]

M. Barnes

T53

M. Leveridge

T61 M. Teall

T37

M.D. Bass

T53 Maciej Smulkowski

T10

Mack S

T40 Maeda M (加藤 寛人) T70 Magnus C. Eriksson

T10

Manabe I (真鍋 一郎) T60 Margaret M. Faul

T10

Marianne Langston

T8

28

Maru T (丸 喬光) T30 Maruyama M (丸山 穣) T52 Maruyama R (丸山 玲緒) T59 Masaki T (正木 恒男) T36, T57 Masaki T (正木 恒夫) T45 Matsuda T (松田 貴久) T60 Matsui H (松井 英起) T18, T23, T29 Matsui H (松井 久典) T45, T49, T56, T62 Matsui J (松井 純二) T33, T40 Matsumoto K (松本 清) T68 Matsumoto K (前田 麻希) T70 Matsumoto K (松本 清) T69 Matsumoto S

T20

Matsumoto S (松本 真一) T45 Matsumoto T (松本 孝浩) T18 Matsumoto T (松本 辰美) T39 Matsumoto Y (松本 芳男) T52, T54 Matsuo S (松尾 成喜) T70 Matsuoka T (松浦 郁夫) T70 Matsuura I (峯島 浩) T70 McArthur GA

T38

McLuckey SA

T4 Michael H. Millonig

T13

Mineno Masahiro

T14 Mineshima H (三輪 洋司) T70 Mingkun Fu

T2

Miura S (三浦 正太郎) T35, T42, T44 Miwa K (三輪 憲弘) T36 Miwa Y (宮田 英典) T70 Miyahisa I (宮久 郁夫) T33 Miyajima N (宮嶋 伸行) T52 Miyamoto M (宮本 政臣) T43 Miyanohana Y (宮野鼻 悠平) T21 Miyashita H (宮下 裕久) T19 Mizufune Hideya

T14

Mizukami A (水上 温司) T20, T23 Mizuno Masahiro (水野 正博) T11, T14 Mo Jiang

T8

29

Moen Vollan HK

T59 Momen Shinobu

T48

Momose Yu (百瀬 祐) T74 Mori M (森 正明) T52 Morimoto M (森本 恵) T57 Morita S (森田 滋) T57 Moriwaki T (森脇 俊哉) T63 Mototani H (本谷 英之) T24, T27 Motoyaji T (元屋地 孝士) T30 Mouri K (毛利 恒次) T64 Murata T2. (村田 俊樹) T19 Muto Eigo (武藤 英吾) T9

[N]

N. Brice

T37, T61

Nagai K (永井 克典) T32 Nagai K (永井 淸亮) T56 Nagamori S (永森 収志) T51 Naito M (内藤 幹彦) T32 Naito T (内藤 貴子) T24, T27 Nakagawa H (中川 秀行) T22 Nakagomi S (中込 咲綾) T51 Nakamura K (中村 希巳江) T54 Nakanishi A (中西 淳) T58 Nakano N (中野 奈央) T70 Nakashima Kosuke (中島 康祐) T26, T29 Nakata D (中田 大介) T36, T45 Nakayama M (中山 政治) T41, T50 Nara H (奈良 洋) T24, T27 Naya M (納屋 聖人) T70 Negoro Nobuyuki (根来 伸行) T19, T17, T74 Nguyen J

T31

Nick Yankauskas

T7 Nikolsky Y

T59

Nishigaki N (西垣 信裕) T23 Nishihara M (西原 光洋) T64 Nishikawa H (西川 久夫) T43 Nishimura S (西村 智) T60

30

Nishiyama K (西山 啓次) T43, T46 Noyori H (則武 健一) T70 Numasawa-Kuroiwa Y (沼澤 祐子) T58 Nunomura S

T34

[O]

Obayashi Y (大林 由佳) T54 Ochi K (越智 梢) T60 Oda A (小田 明) T51 Odani T (小谷 知之) T18, T19 ,T21 Ogawa K (小川 和雅) T29, T40, T41 Ogawa Y (小川 佳宏) T60 Ogi K (大儀 和宏) T52 Ohgaki R (大垣 隆一) T51 Ohkura S (大蔵 聡) T56, T62 Ohoka N (大岡 伸通) T32 Ohra T (邑楽 泰一) T23 Ohta H (太田 浩之) T22 Ohta T (野寄 広子) T70 Ohta Y (大田 義一) T55 Ohtaki T (大瀧 徹也) T45 Ohyabu N (大藪 紀雄) T23 Okada K

T20, T31

Okada K (岡田 健吾) T30 Okada Y (岡田 洋平) T58 Okamoto Y (岡本 祐幸) T71 Okamura H (岡村 裕昭) T56, T62 Okanishi Satoshi (岡西 聡) T48 Okano H (岡野 栄之) T58 Okayama Y

T34

Oki H (沖 英幸) T24, T26, T27 Oku H (大田 泰史) T70 Okubo S

T20

Okuda T (奥田 照明) T63, T66 Okuhira K (奥平 桂一郎) T32 Onishi T (大西 智裕) T54 Ono A (奥 春孝) T70 Ono M (小野 みどり) T23

31

Ono Yuujirou (小野 祐二朗) T9 Oosawa M (大澤 壮登) T23 Ooshima, Hiroshi (大嶋 寛) T16 Osaka H (小坂 仁) T58 Ota H (太田 浩之) T21 Ouchi Takashi (大内 卓) T9, T15 Oyama M (大山 学) T58

[P]

P. Kubes

T53

P. Martin

T53 Parmar A

T40

Parton L

T40 Peluffo G

T59

Pham C

T72 Polyak K

T59

[Q]

Qing Lu

T2

[R]

R. Newman

T37

R. Patel

T37, T61 Ra C

T34

Richard D. Braatz

TT8 Rikimaru K (力丸 健太郎) T19 Robert Roginksi

T6

Rueda OM

T59 Russnes HG

T59

[S]

S. Almond

T37

S. Mack

T61 S.A

T1

Saikatendu K

T20 Sakamoto K (坂本 光平) T62 Sakuma K (佐久間 健介) T52 Sakurai T (桜井 卓) T40, T41, T50

32

Sameshima T (鮫島 知哉) T33 Santou T (山東 尚) T24, T27 Sasada R (佐々田 玲子) T36 Sasaki S (佐々木 聡) T29 Sasaki Shinobu (佐々木 忍) T74 Sasaki-Sakamoto T

T34

Sato F (佐藤 文彦) T28 Sato K (佐藤 健二郎) T19, T24, T27 Sato K (佐藤 恵一朗) T68, T69 Sawai Yasuhiro (澤井 泰宏) T11 Schmidt ER

T65

Sera Misayo (瀬良 美佐代) T9, T14 Setoh M1 (瀬藤 正記) T21 Shibata N (柴田 識人) T32 Shibata S (芝田 晋介) T58 Shimada M (島田 満之) T35, T42, T44 Shimizu T (小野 敦) T70 Shimizu Y (清水 裕二) T18, T29 Shimojo M (下条 雅人) T18 Shimomura K (清水 達也) T70 Shinohara T (篠原 徳之) T52 Shinozawa E (篠澤 恵巳子) T44 Shiotani S (塩谷 紗知子) T23 Shiraishi E (白石（橋本）絵理) T21 Shirakawa I (白川 伊吹) T60 Shirotsuka Y (城塚 康毅) T68 Shoji M (庄司 昌伸) T58 Siedem CS

T23

Snell G

T31 Sogabe S (曽我部 智) T23 Srivastava A

T31

Stafford S

T40 Steven Pfeiffer

T10

Steven V. Ley

T15 Suganami T (菅波 孝祥) T60 Sugimoto H (杉本 浩通) T19 Sugimoto T (杉本 貴裕) T23 Sun H

T59

33

Suzuki A (鈴木 敦子) T22, T45 Suzuki Kazunori (鈴木 一典) T26 Suzuki S (鈴木 俊也) T57 Sykes A

T40

[T]

Tabata Takashi (田畑 隆志) T9 Takagi S (髙木 慎二) T55, T59 Takagi T (髙木 輝文) T28 Takahashi J (高橋 順三) T64 Takahashi K (高橋 和利) T58 Takahashi T (高橋 孝雄) T58 Takai Takafumi (高井 隆文) T12 Takakura I (下村 和裕) T70 Takasuga, Masahiro (高須賀 正博) T16 Takatsu Y

T45

Takeuchi Koji (武内 浩二) T74 Takeyama M (竹山 道康) T36 Tamura T (田村 寿哉) T55 Tan Min Han

T52

Tanaka A (田中 晃) T36, T45, T56 Tanaka H (田中 秀和) T51 Tanaka M (田中 都) T60 Tanaka R (高倉 郁朗) T70 Tanaka T (田中 知己) T56, T62 Tanaka T (田中 稔祐) T71 Tang TP

T23

Taniguchi Takahiko (谷口 孝彦) T26 Tarui N (樽井 直樹) T28, T30 Tateishi T (田中 亮太) T70 Tawada Hiroyuki (多和田 紘之) T9 Terao Y (寺尾 寧子) T22 Terauchi J (寺内 淳) T22, T24, T27 Terui T

T34

Tominaga Y (富永 優子) T70 Tozawa R (兎澤 隆一) T35, T42, T44, T57 Tsuchimori N (土森 登) T39 Tsujihata Y (辻畑 善行) T19, T47

34

Tsukamoto T (塚本 徹哉) T43

[U]

Uchikawa Osamu (内川 治) T12, T24, T27 Ueda Tsuyoshi

T14

Uejima H (上島 宗之) T51 Uesugi T (上杉 透) T70 Umeyama Y (梅山 夕香里) T66 Urakawa C (浦川 千鶴) T70

[V]

V.R.L. Kyle

T25

Vaske C

T59

[W]

W.H. Colledge

T25

Wakabayashi Y (若林 嘉浩) T56, T62 Waldeck KL

T38

Walsh L

T20 Watanabe T (渡邉 辰也) T36, T45 William F. Kiesman

T10

Wiriyasermkul P

T51 Wu H

T20

Wu Z

T59

[X]

Xu R

T72

[Y]

Yabe K (矢部 薫) T70 Yamagata K (山形 要人) T51 Yamaguchi M (山口 昌史) T45 Yamamoto S (山本 昌司) T59 Yamamoto Y (山本 善雄) T24, T27 Yamamura T (山村 崇) T62 Yamanaka S (山中 伸弥) T58 Yamano Mitsuhisa (山野 光久) T11, T14 Yamano, Toru (山野 徹) T17

35

Yamaoka Masuo (山岡 万寿夫) T76 Yamasaki Masashi (山嵜 将司) T75 Yamasaki S (山崎 晶) T60 Yamashita A (山下 晃人) T70 Yamashita Makoto (山下 誠) T9 Yamashita T (山下 輝芳) T69 Yamashita, Masayuki (山下 真之) T17 Yamauchi T (横井 亮平) T70 Yamauchi T (山内 俊明) T70, T69 Yano J

T31

Yano T (矢野 隆) T54 Yao S (八尾 修平) T52 Yasuma Tsuneo (安間 常雄) T17, T74 Yokoi R (江馬 眞) T70 Yoneyama T (米山 智城) T65 Yoshikawa Masato (吉川 真人) T22, T26 Yoshikawa Satoru

T48

Yoshimatsu M (吉松 美恵) T36 Yoshimura Naoki

T48

[Z]

Zanka Atsuhiko

T14

Zeng L

T72 Zhang Y

T72

Zhao X

T59 Zhilong Zhu

T8

Zucca M

T59

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