6533b82bfe1ef96bd128e0a1

RESEARCH PRODUCT

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 PeiferFrank TotzkeOliver KohlbacherNina HämmerleGerd DannhardtAgata KrasowskiChristoph SchächteleStefan Laufer

subject

Indole testModels MolecularBinding SitesIndolesMolecular modelStereochemistryChemistryKinaseMolecular Sequence DataBiological activitySequence alignmentCrystallography X-RayVascular Endothelial Growth Factor Receptor-3Vascular Endothelial Growth Factor Receptor-2Drug DiscoveryMolecular MedicinePyrrolesAmino Acid SequenceBinding siteSelectivityPeptide sequenceHydrophobic and Hydrophilic Interactions

description

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.

yearjournalcountryeditionlanguage
2006-12-08Journal of medicinal chemistry
10.1021/jm0609871https://pubmed.ncbi.nlm.nih.gov/17149885