Flipped out: Structure-guided design of selective pyrazolylpyrrole ERK inhibitors

被引：107

作者：

Aronov, Alex M. ^{[1
]}

Baker, Christopher ^{[1
]}

Bemis, Guy W. ^{[1
]}

Cao, Jingrong ^{[1
]}

Chen, Guanjing ^{[1
]}

Ford, Pamella J. ^{[1
]}

Germann, Ursula A. ^{[1
]}

Green, Jeremy ^{[1
]}

Hale, Michael R. ^{[1
]}

Jacobs, Marc ^{[1
]}

Janetka, James W. ^{[1
]}

Maltais, Francois ^{[1
]}

Martinez-Botella, Gabriel ^{[1
]}

Namchuk, Mark N. ^{[1
]}

Straub, Judy ^{[1
]}

Tang, Qing ^{[1
]}

Xie, Xiaoling ^{[1
]}

机构：

[1] Vertex Pharmaceut Inc, Cambridge, MA 02139 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2007年 / 50卷 / 06期

关键词：

D O I：

10.1021/jm061381f

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The Ras/Raf/MEK/ERK signal transduction is a key oncogenic pathway implicated in a variety of human cancers. We have identified a novel series of pyrazolylpyrroles as inhibitors of ERK. Aided by the discovery of two distinct binding modes for the pyrazolylpyrrole scaffold, structure-guided optimization culminated in the discovery of 6p, a potent and selective inhibitor of ERK.

引用

页码：1280 / 1287

页数：8

共 50 条

[41] Structure-Guided Discovery of Aminoquinazolines as Brain-Penetrant and Selective LRRK2 Inhibitors
Keylor, Mitchell H.
Gulati, Anmol
Kattar, Solomon D.
Johnson, Rebecca E.
Chau, Ryan W.
Margrey, Kaila A.
Ardolino, Michael J.
Zarate, Cayetana
Poremba, Kelsey E.
Simov, Vladimir
Morriello, Gregori J.
Acton, John J.
Pio, Barbara
Yan, Xin
Palte, Rachel L.
McMinn, Spencer E.
Nogle, Lisa
Lesburg, Charles A.
Adpressa, Donovon
Lin, Shishi
Neelamkavil, Santhosh
Liu, Ping
Su, Jing
Hegde, Laxminarayan G.
Woodhouse, Janice D.
Faltus, Robert
Xiong, Tina
Ciaccio, Paul J.
Piesvaux, Jennifer
Otte, Karin M.
Wood, Harold B.
Kennedy, Matthew E.
Bennett, David Jonathan
DiMauro, Erin F.
Fell, Matthew J.
Fuller, Peter H.
JOURNAL OF MEDICINAL CHEMISTRY, 2022, 65 (01) : 838 - 856
[42] Structure-Guided Design of Novel L-Cysteine Derivatives as Potent KSP Inhibitors
Ogo, Naohisa
Ishikawa, Yoshinobu
Sawada, Jun-ichi
Matsuno, Kenji
Hashimoto, Akihiro
Asai, Akira
ACS MEDICINAL CHEMISTRY LETTERS, 2015, 6 (09): : 1004 - 1009
[43] Structure-Guided Design, Synthesis, and Antivirulence Assessment of Covalent Staphylococcus aureus Sortase A Inhibitors
Yue, Chuan
Yuan, Ziqi
Xu, Guobin
Guan, Xiang-Na
Wei, Bingyan
Yao, Hequan
Yang, Cai-Guang
Zhang, Tao
JOURNAL OF MEDICINAL CHEMISTRY, 2024, 67 (02) : 1127 - 1146
[44] Structure-guided design of novel Trypanosoma brucei Methionyl-tRNA synthetase inhibitors
Huang, Wenlin
Zhang, Zhongsheng
Barros-Alvarez, Ximena
Koh, Cho Yeow
Ranade, Ranae M.
Gillespie, J. Robert
Creason, Sharon A.
Shibata, Sayaka
Verlinde, Christophe L. M. J.
Hol, Wim G. J.
Buckner, Frederick S.
Fan, Erkang
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2016, 124 : 1081 - 1092
[45] Structure-Guided Design of Selective Epac1 and Epac2 Agonists
Schwede, Frank
Bertinetti, Daniela
Langerijs, Carianne N.
Hadders, Michael A.
Wienk, Hans
Ellenbroek, Johanne H.
de Koning, Eelco J. P.
Bos, Johannes L.
Herberg, Friedrich W.
Genieser, Hans-Gottfried
Janssen, Richard A. J.
Rehmann, Holger
PLOS BIOLOGY, 2015, 13 (01):
[46] Structure-guided design of a selective inhibitor of the methyltransferase KMT9 with cellular activity
Sheng Wang
Sebastian O. Klein
Sylvia Urban
Maximilian Staudt
Nicolas P. F. Barthes
Dominica Willmann
Johannes Bacher
Manuela Sum
Helena Bauer
Ling Peng
Georg A. Rennar
Christian Gratzke
Katrin M. Schüle
Lin Zhang
Oliver Einsle
Holger Greschik
Calum MacLeod
Christopher G. Thomson
Manfred Jung
Eric Metzger
Roland Schüle
Nature Communications, 15
[47] Structure-Guided Design and Procognitive Assessment of a Potent and Selective Phosphodiesterase 2A Inhibitor
Stachel, Shawn J.
Berger, Richard
Nomland, Ashley B.
Ginnetti, Anthony T.
Paone, Daniel, V
Wang, Deping
Puri, Vanita
Lange, Henry
Drott, Jason
Lu, Jun
Marcus, Jacob
Dwyer, Michael P.
Su, Sokreine
Uslaner, Jason M.
Smith, Sean M.
ACS MEDICINAL CHEMISTRY LETTERS, 2018, 9 (08): : 815 - 820
[48] Structure-guided design of a selective inhibitor of the methyltransferase KMT9 with cellular activity
Wang, Sheng
Klein, Sebastian O.
Urban, Sylvia
Staudt, Maximilian
Barthes, Nicolas P. F.
Willmann, Dominica
Bacher, Johannes
Sum, Manuela
Bauer, Helena
Peng, Ling
Rennar, Georg A.
Gratzke, Christian
Schuele, Katrin M.
Zhang, Lin
Einsle, Oliver
Greschik, Holger
Macleod, Calum
Thomson, Christopher G.
Jung, Manfred
Metzger, Eric
Schuele, Roland
NATURE COMMUNICATIONS, 2024, 15 (01)
[49] MOLECULAR DYNAMICS AND FREE ENERGY ANALYSES OF ERK2-PYRAZOLYLPYRROLE INHIBITORS INTERACTIONS: INSIGHT INTO STRUCTURE-BASED LIGAND DESIGN
Zhan, Jin-Hui
Zhao, Xi
Huang, Xu-Ri
Sun, Chia-Chung
JOURNAL OF THEORETICAL & COMPUTATIONAL CHEMISTRY, 2009, 8 (05): : 887 - 908
[50] Structure guided design of a series of selective pyrrolopyrimidinone MARK inhibitors
Katz, Jason D.
Haidle, Andrew
Childers, Kaleen K.
Zabierek, Anna A.
Jewell, James P.
Hou, Yongquan
Altman, Michael D.
Szewczak, Alexander
Chen, Dapeng
Harsch, Andreas
Hayashi, Mansuo
Warren, Lee
Hutton, Michael
Nuthall, Hugh
Su, Hua-Poo
Munshi, Sanjeev
Stanton, Matt G.
Davies, Ian W.
Munoz, Ben
Northrup, Alan
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2017, 27 (01) : 114 - 120

← 1 2 3 4 5 →