Flipped out: structure-guided design of selective pyrazolylpyrrole ERK inhibitors.

Article Details

Citation

Aronov AM, Baker C, Bemis GW, Cao J, Chen G, Ford PJ, Germann UA, Green J, Hale MR, Jacobs M, Janetka JW, Maltais F, Martinez-Botella G, Namchuk MN, Straub J, Tang Q, Xie X

Flipped out: structure-guided design of selective pyrazolylpyrrole ERK inhibitors.

J Med Chem. 2007 Mar 22;50(6):1280-7. Epub 2007 Feb 15.

PubMed ID
17300186 [ View in PubMed
]
Abstract

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.

DrugBank Data that Cites this Article

Polypeptides
NameUniProt ID
Mitogen-activated protein kinase 1P28482Details
Binding Properties
DrugTargetPropertyMeasurementpHTemperature (°C)
(S)-N-(1-(3-CHLORO-4-FLUOROPHENYL)-2-HYDROXYETHYL)-4-(4-(3-CHLOROPHENYL)-1H-PYRAZOL-3-YL)-1H-PYRROLE-2-CARBOXAMIDEMitogen-activated protein kinase 1Ki (nM)27.530Details
N-BENZYL-4-[4-(3-CHLOROPHENYL)-1H-PYRAZOL-3-YL]-1H-PYRROLE-2-CARBOXAMIDEMitogen-activated protein kinase 1Ki (nM)867.530Details
N-BENZYL-4-[4-(3-CHLOROPHENYL)-1H-PYRAZOL-3-YL]-1H-PYRROLE-2-CARBOXAMIDEMitogen-activated protein kinase 10Ki (nM)5507.530Details
N,N-DIMETHYL-4-(4-PHENYL-1H-PYRAZOL-3-YL)-1H-PYRROLE-2-CARBOXAMIDEMitogen-activated protein kinase 1Ki (nM)23007.530Details