Discovery and structure activity relationship study of novel indazole amide inhibitors for extracellular signal-regulated kinase1/2 (ERK1/2).
The discovery and optimization of a series of indazole amide based extracellular signal-regulated kinase inhibitors via structure/knowledge based drug design and kinase screen is reported. The optimized compounds demonstrate potent inhibition of ERK1/2 enzyme activity, growth of BRAF mutant HT29 cells and ERK signaling in HT29 cells.
Green Valley Research Institute, Green Valley Pharmaceutical Co., Ltd, 421, Niudun Road, Zhangjiang Hi-tech Park, Pudong New Area, Shanghai 201203, China.
Lei
L
Li
Shanghai Institute of Materia Medica, Chinese Academy of Science, 555 Zuchongzhi Road, Zhangjiang Hi-tech Park, Pudong New Area, Shanghai 201203, China.
Feifei
F
Liu
Shanghai Institute of Materia Medica, Chinese Academy of Science, 555 Zuchongzhi Road, Zhangjiang Hi-tech Park, Pudong New Area, Shanghai 201203, China.
Nan
N
Jin
Shanghai Institute of Materia Medica, Chinese Academy of Science, 555 Zuchongzhi Road, Zhangjiang Hi-tech Park, Pudong New Area, Shanghai 201203, China.
Shuai
S
Tang
Green Valley Research Institute, Green Valley Pharmaceutical Co., Ltd, 421, Niudun Road, Zhangjiang Hi-tech Park, Pudong New Area, Shanghai 201203, China; Shanghai Institute of Materia Medica, Chinese Academy of Science, 555 Zuchongzhi Road, Zhangjiang Hi-tech Park, Pudong New Area, Shanghai 201203, China.
Zhuxi
Z
Chen
Shanghai Institute of Materia Medica, Chinese Academy of Science, 555 Zuchongzhi Road, Zhangjiang Hi-tech Park, Pudong New Area, Shanghai 201203, China.
Xiaotong
X
Yang
Shanghai Institute of Materia Medica, Chinese Academy of Science, 555 Zuchongzhi Road, Zhangjiang Hi-tech Park, Pudong New Area, Shanghai 201203, China.
Jian
J
Ding
Shanghai Institute of Materia Medica, Chinese Academy of Science, 555 Zuchongzhi Road, Zhangjiang Hi-tech Park, Pudong New Area, Shanghai 201203, China.
Meiyu
M
Geng
Green Valley Research Institute, Green Valley Pharmaceutical Co., Ltd, 421, Niudun Road, Zhangjiang Hi-tech Park, Pudong New Area, Shanghai 201203, China.
Lei
L
Jiang
Shanghai Institute of Materia Medica, Chinese Academy of Science, 555 Zuchongzhi Road, Zhangjiang Hi-tech Park, Pudong New Area, Shanghai 201203, China.
Min
M
Huang
Green Valley Research Institute, Green Valley Pharmaceutical Co., Ltd, 421, Niudun Road, Zhangjiang Hi-tech Park, Pudong New Area, Shanghai 201203, China.
Jianhua
J
Cao
D000577:Amides; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D019073:HT29 Cells; D006801:Humans; D007191:Indazoles; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D000577:Amides; D007191:Indazoles; D047428:Protein Kinase Inhibitors; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3
ERK1/2 kinase inhibitor; Indazole amide; Structure based drug design