Design, Synthesis, and Biological Evaluation of MEK PROTACs

被引：39

作者：

Vollmer, Stefan ^{[1
,3
]}

Cunoosamy, Danen ^{[1
,3
]}

Lv, Huafei ^{[4
]}

Feng, Huanxi ^{[4
]}

Li, Xia ^{[4
]}

Nan, Ziyang ^{[4
]}

Yang, Wenzhen ^{[4
]}

Perry, Matthew W. D. ^{[1
,2
,3
]}

机构：

[1] AstraZeneca, BioPharmaceut R&D, Translat Sci & Expt Med, S-43183 Gothenburg, Sweden

[2] AstraZeneca, BioPharmaceut R&D, Med Chem, S-43183 Gothenburg, Sweden

[3] AstraZeneca, BioPharmaceut R&D, Res & Early Dev, RIA, S-43183 Gothenburg, Sweden

[4] Pharmaron Beijing Co Ltd, BDA, 6 Taihe Rd, Beijing 100176, Peoples R China

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2020年 / 63卷 / 01期

关键词：

INDUCED PROTEIN-DEGRADATION; INHIBITORS; RAF;

D O I：

10.1021/acs.jmedchem.9b00810

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

PROteolysis TArgeting Chimeras (PROTACs) targeting the degradation of MEK have been designed based on allosteric MEK inhibitors. Inhibition of the phosphorylation of ERK1/2 was less effective with the PROTACs than a small-molecule inhibitor; the best PROTACs, however, were more effective in inhibiting proliferation of A375 cells than an inhibitor.

引用

页码：157 / 162

页数：6

共 50 条

[1] Design, synthesis and biological evaluation of MNK-PROTACs
Sun, Xue
Wu, Qingyun
Bu, Hong
Pei, Yifeng
Guan, Dezhong
Guo, Shi
Zhou, Jinpei
Zhang, Huibin
MOLECULAR DIVERSITY, 2024, 28 (06) : 3783 - 3800
[2] Design, synthesis and biological evaluation of tyrosinase-targeting PROTACs
Fu, Dingqiang
Yuan, Yi
Qin, Fengming
Xu, Yan
Cui, Xin
Li, Guangxun
Yao, Shaohua
Deng, Yun
Tang, Zhuo
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2021, 226
[3] Synthesis and biological evaluation of niclosamide PROTACs
Munoz, Erick
Chen, Guanglin
Hossain, Ahamed
Wu, Sitong
Nava, Esveidy Oceguera
Hang, Jasmine
Lee, Tong
Zhang, Qiang
Wang, Guangdi
Chen, Qiao-Hong
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2022, 72
[4] Design, synthesis, and biological evaluation of RIPK1-targeting PROTACs
Zhang, Hefeng
Zhang, Shuonan
Wang, Tianchen
Lan, Yaohan
Dai, Yang
Peng, Xia
An, Yuxiang
Xue, Yi
Ai, Jing
Duan, Wenhu
MOLECULAR DIVERSITY, 2025,
[5] Design, synthesis and biological evaluation of KRASG12C-PROTACs
Zhang, Xiaoyi
Zhao, Tong
Sun, Minghao
Li, Pei
Lai, Mengzhen
Xie, Lingfeng
Chen, Jiaying
Ding, Jian
Xie, Hua
Zhou, Jinpei
Zhang, Huibin
BIOORGANIC & MEDICINAL CHEMISTRY, 2023, 78
[6] Design, synthesis, and biological evaluation of potent FAK-degrading PROTACs
Qin, Qiaohua
Wang, Ruifeng
Fu, Qinglin
Zhang, Guoqi
Wu, Tianxiao
Liu, Nian
Lv, Ruicheng
Yin, Wenbo
Sun, Yin
Sun, Yixiang
Zhao, Dongmei
Cheng, Maosheng
JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, 2022, 37 (01) : 2241 - 2255
[7] Design, synthesis, and biological evaluation of novel FGFR1 PROTACs
Wang, Yu-Wei
Gao, Yu-Hui
Wang, Cheng
Zhang, Ping-Fan
Wang, Min
Lan, Li
Liu, Jing-Ying
Shi, Lei
Sun, Li-Ping
BIOORGANIC CHEMISTRY, 2025, 155
[8] Design, Synthesis, and Biological Evaluation of IRAK4-Targeting PROTACs
Chen, Yun
Ning, Yi
Bai, Gang
Tong, Linjiang
Zhang, Tao
Zhou, Jinpei
Zhang, Huibin
Xie, Hua
Ding, Jian
Duan, Wenhu
ACS MEDICINAL CHEMISTRY LETTERS, 2021, 12 (01): : 82 - 87
[9] Design, synthesis, and biological evaluation of small molecule PROTACs for potential anticancer effects
Yang Da
Shaodong Liu
Pei Lin
Feng Wang
Renjie Yan
Yongzhi Shu
Jun Lin
Medicinal Chemistry Research, 2020, 29 : 334 - 340
[10] Design, synthesis, and biological evaluation of small molecule PROTACs for potential anticancer effects
Da, Yang
Liu, Shaodong
Lin, Pei
Wang, Feng
Yan, Renjie
Shu, Yongzhi
Lin, Jun
MEDICINAL CHEMISTRY RESEARCH, 2020, 29 (02) : 334 - 340

← 1 2 3 4 5 →