Discovery of an Aurora kinase inhibitor through site-specific dynamic combinatorial chemistry.

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Cancilla MT, He MM, Viswanathan N, Simmons RL, Taylor M, Fung AD, Cao K, Erlanson DA

Discovery of an Aurora kinase inhibitor through site-specific dynamic combinatorial chemistry.

Bioorg Med Chem Lett. 2008 Jul 15;18(14):3978-81. doi: 10.1016/j.bmcl.2008.06.011. Epub 2008 Jun 10.

PubMed ID

18579375 [ View in PubMed

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Abstract

We demonstrate a fragment-based lead discovery method that combines site-directed ligand discovery with dynamic combinatorial chemistry. Our technique targets dynamic combinatorial screening to a specified region of a protein by using reversible disulfide chemistry. We have used this technology to rapidly identify inhibitors of the drug target Aurora A that span the purine-binding site and the adaptive pocket of the kinase. The binding mode of a noncovalent inhibitor has been further characterized through crystallography.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
N-butyl-3-{[6-(9H-purin-6-ylamino)hexanoyl]amino}benzamide	Aurora kinase A	IC 50 (nM)	2900	N/A	N/A	Details