Several of these ATP-competitive inhibitors are currently in clinical development.
In the present review we describe step-by-step the HTS performed for selecting aurora kinase inhibitors in the French patrimonial library .
The approach followed to validate the hits is outlined and a decision tree is proposed., 0.4 µM ATP, 0.4 m M DTT, p H 7.5. The reaction was started by the addition of the recombinant kinase domain.
We propose a decision tree that could be adapted to most Aurora kinases are a family of serine/threonine protein kinases that play a key role in mitotic progression [1,2].
In human, three aurora kinases have been identified: A, B and C.
Taking into account that probably several screenings have already been performed on the same library, it is advisable to ask for the removal of all targets previously identified as kinase inhibitors.
Before deciding which molecules to select for further studies, you might look to the developed structures.
When the kinase is inactive the ATP concentration is high.
Each point represents a molecule, the yellow points are controls in the presence of staurosporine and blue points the full active kinase in the absence of molecule. We selected molecules that inhibit aurora kinase by more than 80% at 15 µM.
The next question was: how to deal with these 195 molecules?