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J-GLOBAL ID：201802227404012737   整理番号：18A0262265

新しい不可逆的パン線維芽細胞成長因子受容体(FGFR)阻害剤としての2-オキソ-3, 4-dihydropyrimido[4, 5-d]ピリミジニル誘導体【Powered by NICT】

2-Oxo-3, 4-dihydropyrimido[4, 5-d]pyrimidinyl derivatives as new irreversible pan fibroblast growth factor receptor (FGFR) inhibitors

著者 (23件)： Li Xueqiang (Guangzhou Institutes of Biomedicine and Health, Guangdong Provincial Key Laboratory of Biocomputing, Chinese Academy of Sciences, No.190 Kaiyuan Avenue, Guangzhou 510530, China) ,  Li Xueqiang (University of Chinese Academy of Sciences, No. 19 Yuquan Road, Beijing 100049, China) ,  Guise Christopher P. (Auckland Cancer Society Research Centre, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand) ,  Guise Christopher P. (Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand) ,  Taghipouran Rana (Auckland Cancer Society Research Centre, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand) ,  Yosaatmadja Yuliana (School of Biological Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand) ,  Ashoorzadeh Amir (Auckland Cancer Society Research Centre, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand) ,  Paik Woo-Kyong (School of Biological Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand) ,  Squire Christopher J. (Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand) ,  Squire Christopher J. (School of Biological Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand) ,  Jiang Shuang (Guangzhou Institutes of Biomedicine and Health, Guangdong Provincial Key Laboratory of Biocomputing, Chinese Academy of Sciences, No.190 Kaiyuan Avenue, Guangzhou 510530, China) ,  Jiang Shuang (University of Chinese Academy of Sciences, No. 19 Yuquan Road, Beijing 100049, China) ,  Luo Jinfeng (Guangzhou Institutes of Biomedicine and Health, Guangdong Provincial Key Laboratory of Biocomputing, Chinese Academy of Sciences, No.190 Kaiyuan Avenue, Guangzhou 510530, China) ,  Xu Yong (Guangzhou Institutes of Biomedicine and Health, Guangdong Provincial Key Laboratory of Biocomputing, Chinese Academy of Sciences, No.190 Kaiyuan Avenue, Guangzhou 510530, China) ,  Tu Zheng-Chao (Guangzhou Institutes of Biomedicine and Health, Guangdong Provincial Key Laboratory of Biocomputing, Chinese Academy of Sciences, No.190 Kaiyuan Avenue, Guangzhou 510530, China) ,  Lu Xiaoyun (School of Pharmacy, Jinan University, No. 601 Huangpu Avenue West, Guangzhou 510632, China) ,  Ren Xiaomei (School of Pharmacy, Jinan University, No. 601 Huangpu Avenue West, Guangzhou 510632, China) ,  Patterson Adam V. (Auckland Cancer Society Research Centre, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand) ,  Patterson Adam V. (Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand) ,  Smaill Jeff B. (Auckland Cancer Society Research Centre, School of Medical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand) ,  Smaill Jeff B. (Maurice Wilkins Centre for Molecular Biodiscovery, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand) ,  Ding Ke (Guangzhou Institutes of Biomedicine and Health, Guangdong Provincial Key Laboratory of Biocomputing, Chinese Academy of Sciences, No.190 Kaiyuan Avenue, Guangzhou 510530, China) ,  Ding Ke (School of Pharmacy, Jinan University, No. 601 Huangpu Avenue West, Guangzhou 510632, China)
資料名： European Journal of Medicinal Chemistry  (European Journal of Medicinal Chemistry)
巻： 135  ページ： 531-543  発行年： 2017年 
JST資料番号： E0845A  ISSN： 0223-5234  資料種別： 逐次刊行物 (A)
記事区分： 原著論文  発行国： オランダ (NLD)  言語： 英語 (EN)

抄録/ポイント： 一連2-オキソ-3, 4-dihydropyrimido[4,5-d]-ピリミジニル誘導体をFGFRファミリーの新しい不可逆的阻害剤として設計し,合成した。最も有望な化合物2Lの一つはFGFR1/2/3を阻害しIC_50値1.06,0.84と5.38nMであったが,FGFR4に対するその効力は一桁減少した。化合物2Lは低ナノモルIC_50値とFGFR1増幅H520肺非小細胞癌細胞,FGFR2増幅SUM52乳癌細胞およびFGFR3増幅SW780膀胱癌細胞の増殖を強く抑制するが,四FGFR陰性癌細胞株に対する,低マイクロモルIC_50値と有意に弱かった。生物学的研究は,FGFR1 3標的キナーゼを持つ分子の不可逆的結合を確認した。化合物2Lがさらに進んだ抗癌薬発見のための有望な新規リード化合物として役立つ可能性がある。Copyright 2018 Elsevier B.V., Amsterdam. All rights reserved. Translated from English into Japanese by JST.【Powered by NICT】

シソーラス用語： *線維芽細胞 ,  非小細胞肺癌 ,  *不可逆性 ,  抗腫瘍薬 ,  *FGF受容体
準シソーラス用語： リード化合物 ,  キナーゼ ,  腫瘍細胞株 ,  FGF受容体3 ,  乳癌細胞 ,  FGF受容体2 ,  FGF受容体4 ,  FGF受容体1 ,  *阻害剤 ,  成長因子受容体 , 【Automatic Indexing@JST】

著者キーワード (3件)： FGFR ,  2-オキソ-34-dihydropyrimido[45-d]ピリミジニル誘導体 ,  不可逆阻害剤

分類 (5件)： 酵素製剤・酵素阻害剤の基礎研究  (GW21010W) ,  薬物の構造活性相関  (GV01050B) ,  薬物の合成  (GV01030F) ,  酵素一般  (EB09010D) ,  抗腫よう薬の基礎研究  (GW16010A)

タイトルに関連する用語 (6件)： パン ,  線維芽細胞成長因子 ,  受容体 ,  FGFR ,  阻害剤 ,  誘導体