3K5U: Identification, SAR Studies and X-ray Cocrystal Analysis of a Novel Furano-pyrimidine Aurora Kinase A Inhibitor

Herein we reveal a simple method for the identification of novel Aurora kinase A inhibitors through substructure searching of an in-house compound library to select compounds for testing. A hydrazone fragment conferring Aurora kinase activity and heterocyclic rings most frequently reported in kinase inhibitors were used as substructure queries to filter the in-house compound library collection prior to testing. Five new series of Aurora kinase inhibitors were identified through this strategy, with IC(50) values ranging from approximately 300 nM to approximately 15 microM, by testing only 133 compounds from a database of approximately 125,000 compounds. Structure-activity relationship studies and X-ray co-crystallographic analysis of the most potent compound, a furanopyrimidine derivative with an IC(50) value of 309 nM toward Aurora kinase A, were carried out. The knowledge gained through these studies could help in the future design of potent Aurora kinase inhibitors.
PDB ID: 3K5UDownload
MMDB ID: 85450
PDB Deposition Date: 2009/10/8
Updated in MMDB: 2017/11
Experimental Method:
x-ray diffraction
Resolution: 2.35  Å
Source Organism:
Similar Structures:
Biological Unit for 3K5U: monomeric; determined by author and by software (PISA)
Molecular Components in 3K5U
Label Count Molecule
Protein (1 molecule)
Serine/threonine-protein Kinase 6(Gene symbol: AURKA)
Molecule annotation
Chemical (1 molecule)
* Click molecule labels to explore molecular sequence information.

Citing MMDB