Design of a Cyclin G Associated Kinase (GAK)/Epidermal Growth Factor Receptor (EGFR) Inhibitor Set to Interrogate the Relationship of EGFR and GAK in Chordoma

被引：30
|
作者：
Asquith, Christopher R. M. [1 ,2 ]
Naegeli, Kaleb M. [3 ]
East, Michael P. [2 ]
Laitinen, Tuomo [4 ]
Havener, Tammy M. [3 ]
Wells, Carrow I. [1 ]
Johnson, Gary L. [2 ]
Drewry, David H. [1 ]
Zuercher, William J. [1 ,5 ]
Morris, David C. [3 ]
机构：
[1] Univ N Carolina, UNC Eshelman Sch Pharm, Struct Genom Consortium, Chapel Hill, NC 27599 USA
[2] Univ N Carolina, Sch Med, Dept Pharmacol, Chapel Hill, NC 27599 USA
[3] Univ N Carolina, UNC Catalyst Rare Dis, Chapel Hill, NC 27599 USA
[4] Univ Eastern Finland, Fac Hlth Sci, Sch Pharm, Kuopio 70211, Finland
[5] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA
来源：
JOURNAL OF MEDICINAL CHEMISTRY | 2019年 / 62卷 / 09期
基金：
加拿大创新基金会; 巴西圣保罗研究基金会;
关键词：
4-ANILINOQUINOLINES; EXPRESSION; MUTATIONS;
D O I：
10.1021/acs.jmedchem.9b00350
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
We describe the design of a set of inhibitors to investigate the relationship between cyclin G associated kinase (GAK) and epidermal growth factor receptor (EGFR) in chordoma bone cancers. These compounds were characterized both in vitro and using in cell target engagement assays. The most potent chordoma inhibitors were further characterized in a kinome-wide screen demonstrating narrow spectrum profiles. While we observed a direct correlation between EGFR and antiproliferative effects on chordoma, GAK inhibition appeared to have only a limited effect.
引用
收藏
页码：4772 / 4778
页数：7
相关论文
共 50 条
  • [41] Impact of epidermal growth factor receptor (EGFR) kinase mutations, EGFR gene amplilications, and KRAS mutations on survival of pancreatic adenocarcinoma
    Lee, Jeeyun
    Jang, Kee-Taek
    Ki, Chang-Seok
    Lim, Taekyu
    Park, Young Suk
    Lim, Ho Yeong
    Choi, Dong-Wook
    Kaing, Won Ki
    Park, Keunchil
    Park, Joon Oh
    CANCER, 2007, 109 (08) : 1561 - 1569
  • [42] Effectiveness of Epidermal Growth Factor containing Moisture Cream for treatment of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR TKI)-induced cutaneous toxicities.
    Lee, Sung Yong
    Moon, Jae Young
    Lee, Sang Yeub
    Kim, Je Hyeong
    Shin, Chol
    Shim, Jae Jeong
    In, Kwang Ho
    Yoo, Se Hwa
    Kang, Kyung Ho
    Kim, Jun Suk
    Song, Hae Jun
    JOURNAL OF THORACIC ONCOLOGY, 2009, 4 (09) : S895 - S895
  • [43] 111In-Labeled Immunoconjugates (ICs) Bispecific for the Epidermal Growth Factor Receptor (EGFR) and Cyclin-Dependent Kinase Inhibitor, p27Kip1
    Cornelissen, Bart
    Kersemans, Veerle
    McLarty, Kristin
    Tran, Lara
    Reilly, Raymond M.
    CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS, 2009, 24 (02) : 163 - 173
  • [44] SYNTHESIS OF NOVEL BENZOXAZINONE COMPOUNDS AS EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) TYROSINE KINASE INHIBITORS
    Chen, Shaopeng
    Li, Xuemin
    Wan, Shengbiao
    Jiang, Tao
    SYNTHETIC COMMUNICATIONS, 2012, 42 (19) : 2937 - 2946
  • [45] Design of New Quinazoline Derivative as EGFR (Epidermal Growth Factor Receptor) Inhibitor through Molecular Docking and Dynamics Simulation
    Rasyid, Herlina
    Purwono, Bambang
    Pranowo, Harno Dwi
    INDONESIAN JOURNAL OF CHEMISTRY, 2021, 21 (01) : 201 - 211
  • [46] Does the efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor differ according to the type of EGFR mutation in non-small cell lung cancer?
    Choi, Yong Won
    Choi, Jin-Hyuk
    KOREAN JOURNAL OF INTERNAL MEDICINE, 2017, 32 (03): : 422 - 428
  • [47] Brain tumors in mice are susceptible to blockade of epidermal growth factor receptor (EGFR) with the oral, specific, EGFR-tyrosine kinase inhibitor ZD1839 (Iressa)
    Heimberger, AB
    Learn, CA
    Archer, GE
    McLendon, RE
    Chewning, TA
    Tuck, TL
    Pracyk, JB
    Friedman, AH
    Friedman, HS
    Bigner, DD
    Sampson, JH
    CLINICAL CANCER RESEARCH, 2002, 8 (11) : 3496 - 3502
  • [48] Concomitant Pulmonary Tuberculosis Impair Survival in Advanced Epidermal Growth Factor Receptor (EGFR) Mutant Lung Adenocarcinoma Patients Receiving EGFR-Tyrosine Kinase Inhibitor
    Xie, Yalin
    Su, Ning
    Zhou, Wei
    Lei, An
    Li, Xiang
    Li, Weiwei
    Huang, Zhan
    Cen, Wenchang
    Hu, Jinxing
    CANCER MANAGEMENT AND RESEARCH, 2021, 13 : 7517 - 7526
  • [49] Tumor endothelial cells express epidermal growth factor receptor (EGFR) but not ErbB3 and are responsive to EGF and to EGFR kinase inhibitors
    Amin, DN
    Hida, K
    Bielenberg, DR
    Klagsbrun, M
    CANCER RESEARCH, 2006, 66 (04) : 2173 - 2180
  • [50] Resistance to an irreversible epidermal growth factor receptor (EGFR) inhibitor in EGFR-Mutant lung cancer reveals novel treatment strategies
    Yu, Zhiwei
    Boggon, Titus J.
    Kobayashi, Susumu
    Jin, Cheng
    Ma, Patrick C.
    Dowlati, Afshin
    Kern, Jeffrey A.
    Tenen, Daniel G.
    Halmos, Balazs
    CANCER RESEARCH, 2007, 67 (21) : 10417 - 10427
12345