Discovery of selective irreversible inhibitors for EGFR-T790M

被引:56
|
作者
Zhou, Wenjun [1 ,2 ]
Ercan, Dalia [3 ,4 ]
Jaenne, Pasi A. [3 ,4 ,5 ]
Gray, Nathanael S. [1 ,2 ]
机构
[1] Harvard Univ, Sch Med, Dept Biol Chem & Mol Pharmacol, Boston, MA 02115 USA
[2] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02115 USA
[3] Dana Farber Canc Inst, Lowe Ctr Thorac Oncol, Boston, MA 02115 USA
[4] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA
[5] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA
关键词
EGFR; Kinase inhibitor; T790M; Mutant selective; ACQUIRED-RESISTANCE; KINASE INHIBITORS; EGFR; RECEPTOR; CANCER;
D O I
10.1016/j.bmcl.2010.12.036
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Targeting the epidermal growth factor receptor kinase (EGFR) with ATP-competitive kinase inhibitors results in dramatic but short-lived responses in patients with EGFR mutant non small cell lung cancer. A series of novel covalent EGFR kinase inhibitors with selectivity for the clinically relevant T790M 'gatekeeper' resistance mutation relative to wild-type EGFR were discovered by library screening. A representative compound 3i was obtained through a systematic SAR study guided by mutant EGFR-dependent cellular proliferation assays. (C) 2010 Elsevier Ltd. All rights reserved.
引用
收藏
页码:638 / 643
页数:6
相关论文
共 50 条
  • [21] EGFR-T790M is a rare lung cancer susceptibility allele with enhanced kinase activity
    Vikis, Haris
    Sato, Mitsuo
    James, Michael
    Wang, Daolong
    Wang, Yian
    Wang, Min
    Jia, Dongmei
    Liu, Yan
    Bailey-Wilson, Joan E.
    Amos, Christopher I.
    Pinney, Susan M.
    Petersen, Gloria M.
    de Andrade, Mariza
    Yang, Ping
    Wiest, Jonathan S.
    Fain, Pamela R.
    Schwartz, Ann G.
    Gazdar, Adi
    Gaba, Colette
    Rothschild, Henry
    Mandal, Diptasri
    Kupert, Elena
    Seminara, Daniela
    Viswanathan, Avinash
    Govindan, Ramaswamy
    Minna, John
    Anderson, Marshall W.
    You, Ming
    CANCER RESEARCH, 2007, 67 (10) : 4665 - 4670
  • [22] Discovery of novel and selective reversible inhibitors of EGFR containing the T790M drug resistance mutation with activity in vitro and in vivo
    Schaefer, Gabriele
    Hanan, Emily J.
    Chan, Emily
    Shao, Lily
    Chen, Yuan
    Knight, Jamie
    Yauch, Robert L.
    Schmidt, Stephen
    Sideris, Steven
    Malek, Shiva
    Heffron, Timothy P.
    CANCER RESEARCH, 2014, 74 (19)
  • [23] Combined therapy with EGFR TKI and gambogic acid for overcoming resistance in EGFR-T790M mutant lung cancer
    Wang, Chengde
    Wang, Wei
    Wang, Chaoyang
    Tang, Yijun
    Tian, Hui
    ONCOLOGY LETTERS, 2015, 10 (04) : 2063 - 2066
  • [24] AZD9291, an Irreversible EGFR TKI, Overcomes T790M-Mediated Resistance to EGFR Inhibitors in Lung Cancer
    Cross, Darren A. E.
    Ashton, Susan E.
    Ghiorghiu, Serban
    Eberlein, Cath
    Nebhan, Caroline A.
    Spitzler, Paula J.
    Orme, Jonathon P.
    Finlay, M. Raymond V.
    Ward, Richard A.
    Mellor, Martine J.
    Hughes, Gareth
    Rahi, Amar
    Jacobs, Vivien N.
    Brewer, Monica Red
    Ichihara, Eiki
    Sun, Jing
    Jin, Hailing
    Ballard, Peter
    Al-Kadhimi, Katherine
    Rowlinson, Rachel
    Klinowska, Teresa
    Richmond, Graham H. P.
    Cantarini, Mireille
    Kim, Dong-Wan
    Ranson, Malcolm R.
    Pao, William
    CANCER DISCOVERY, 2014, 4 (09) : 1046 - 1061
  • [25] A Case of a Patient Harboring an EGFR-T790M Mutation Positive in Squamous Cell Lung Cancer
    Runciman, T.
    Aliaga, C.
    Carracedo Gonzales, C.
    JOURNAL OF THORACIC ONCOLOGY, 2018, 13 (10) : S1025 - S1026
  • [26] Noninvasive Identification of EGFR-T790M Mediated Resistant NSCLC Patients Using Plasma CfDNA
    Zheng, Di
    Ye, Xin
    Sun, Yun
    Zhang, Meizhuo
    Wang, Jiying
    Ni, Jian
    Zhang, Haiping
    Zhang, Ling
    Luo, Jie
    Zhang, Jie
    Tang, Liang
    Chen, Gang
    Su, Bo
    Zhu, Guanshan
    Hu, Min
    Gu, Yi
    Xu, Jianfang
    JOURNAL OF THORACIC ONCOLOGY, 2015, 10 (09) : S359 - S359
  • [27] The impact of the EGFR-T790M mutation detection by re-biopsy in EGFR mutant NSCLC patients in the retrospective analysis
    Yoshimura, Akihiro
    Yamada, Tadaaki
    Okura, Naoko
    Uchino, Junji
    Takayama, Koichi
    CANCER RESEARCH, 2019, 79 (13)
  • [28] Pyridones as highly selective, reversible inhibitors of T790M double-mutants of EGFR
    Bryan, Marian C.
    Burdick, Daniel
    Chan, Bryan
    Chen, Yuan
    Dotson, Jennafer
    Eigenbrot, Charles
    Hanan, Emily J.
    Heald, Robert
    Heffron, Timothy P.
    Jackson, Philip
    La, Hank
    Lainchbury, Michael
    Malek, Shiva
    Mann, Sam E.
    Purkey, Hans
    Schaefer, Gabriele
    Schmidt, Stephen
    Seward, Eileen
    Sideris, Steven
    Wang, Shumei
    Yen, Ivana
    Yu, Christine
    ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, 2014, 248
  • [29] 肺癌脑转移患者脑脊液ctDNA样本EGFR-T790M突变分析
    商宏伟
    马光耀
    孙盛斌
    临床肿瘤学杂志, 2018, 23 (10) : 959 - 960
  • [30] A Case of a Patient Harboring an EGFR-T790M Mutation Positive in Squamous Cell Lung Cancer
    Runciman, T.
    Carracedo, C.
    Aliaga, C.
    JOURNAL OF THORACIC ONCOLOGY, 2018, 13 (09) : S179 - S179