Flipped Out: Structure-Guided Design of Selective Pyrazolylpyrrole ERK Inhibitors

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 optimizat...

Ausführliche Beschreibung

Gespeichert in:

Bibliographische Detailangaben
Veröffentlicht in:	Journal of medicinal chemistry 2007-03, Vol.50 (6), p.1280-1287
Hauptverfasser:	Aronov, Alex M, Baker, Christopher, Bemis, Guy W, Cao, Jingrong, Chen, Guanjing, Ford, Pamella J, Germann, Ursula A, Green, Jeremy, Hale, Michael R, Jacobs, Marc, Janetka, James W, Maltais, Francois, Martinez-Botella, Gabriel, Namchuk, Mark N, Straub, Judy, Tang, Qing, Xie, Xiaoling
Format:	Artikel
Sprache:	eng
Schlagworte:	Antineoplastic agents Binding Sites Biological and medical sciences Crystallography, X-Ray General aspects Medical sciences Mitogen-Activated Protein Kinase 1 - antagonists & inhibitors Mitogen-Activated Protein Kinase 1 - chemistry Mitogen-Activated Protein Kinase 3 - antagonists & inhibitors Mitogen-Activated Protein Kinase 3 - chemistry Models, Molecular Molecular Structure Pharmacology. Drug treatments Protein Binding Pyrazoles - chemical synthesis Pyrazoles - chemistry Pyrroles - chemical synthesis Pyrroles - chemistry Quantitative Structure-Activity Relationship Stereoisomerism
Online-Zugang:	Volltext
Tags:	Tag hinzufügen Keine Tags, Fügen Sie den ersten Tag hinzu!

Beschreibung
Zusammenfassung:	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.
ISSN:	0022-2623 1520-4804
DOI:	10.1021/jm061381f