The protein kinase Nek2 plays a key role in centrosome replication and disjunction, a vital event in mitotic spindle formation. Importantly, Nek2 is over-expressed in a variety of cancers.Structure-activity relationship studies for 8-substituted purine inhibitors were undertaken, with X-ray crystallography revealing a non-conventional binding mode within the ATP-binding domain. This presented new interactions to be accessed through structural modification of the scaffold.The synthesis, structure-activity relationships, and structural biology of 8-alkylpurine Nek2 inhibitors will be discussed.

Design and synthesis of 8-substituted purines as inhibitors of Nek2 kinase

243rd National Meeting (2012)

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