Profile and molecular modeling of 3-(indole-3-yl)-4-(3,4,5-trimethoxyphenyl)-1 H-pyrrole-2,5-dione (1) as a highly selective VEGF-R2/3 inhibitor

Christian Peifer; Agata Krasowski; Nina Hämmerle; Oliver Kohlbacher; Gerd Dannhardt; Frank Totzke; Christoph Schächtele; Stefan Laufer

doi:10.1021/jm0609871

Profile and molecular modeling of 3-(indole-3-yl)-4-(3,4,5-trimethoxyphenyl)-1 H-pyrrole-2,5-dione (1) as a highly selective VEGF-R2/3 inhibitor

J Med Chem. 2006 Dec 14;49(25):7549-53. doi: 10.1021/jm0609871.

Authors

Christian Peifer¹, Agata Krasowski, Nina Hämmerle, Oliver Kohlbacher, Gerd Dannhardt, Frank Totzke, Christoph Schächtele, Stefan Laufer

Affiliation

¹ Department of Pharmacy, Eberhard Karls University, Auf der Morgenstelle 8, D-72076 Tübingen, Germany. [email protected]

PMID: 17149885
DOI: 10.1021/jm0609871

Abstract

We report on selectivity profiling of 1 in a panel of 20 protein kinases and molecular modeling indicating 1 to be highly active and selective for VEGF-R2/3. Sequence alignment analysis and detailed insights into the ATP binding pockets of targeted protein kinases from the panel result in a unique structural architecture of VEGF-R2 mainly caused by the hydrophobic pocket I, determining the molecular basis for activity and selectivity of 1.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Binding Sites
Crystallography, X-Ray
Hydrophobic and Hydrophilic Interactions
Indoles / chemical synthesis*
Indoles / chemistry
Models, Molecular*
Molecular Sequence Data
Pyrroles / chemical synthesis*
Pyrroles / chemistry
Vascular Endothelial Growth Factor Receptor-2 / chemistry*
Vascular Endothelial Growth Factor Receptor-3 / chemistry*

Substances

Indoles
Pyrroles
Vascular Endothelial Growth Factor Receptor-2
Vascular Endothelial Growth Factor Receptor-3