Title

Small Molecule Substrate Phosphorylation Site Inhibitors of Protein Kinases: Approaches and Challenges

ACS Citation

Breen, M.E.; Soellner, M.B. Small Molecule Substrate Phosphorylation Site Inhibitors of Protein Kinases: Approaches and Challenges. ACS Chem. Biol. 2015, 10, 1, 175-189.

Abstract

Protein kinases are important mediators of cellular communication and attractive drug targets for many diseases. Although success has been achieved with developing ATP-competitive kinase inhibitors, the disadvantages of ATP-competitive inhibitors have led to increased interest in targeting sites outside of the ATP binding pocket. Kinase inhibitors with substrate-competitive, ATP-noncompetitive binding modes are promising due to the possibility of increased selectivity and better agreement between biochemical and in vitro potency. However, the difficulty of identifying these types of inhibitors has resulted in significantly fewer small molecule substrate phosphorylation site inhibitors being reported compared to ATP-competitive inhibitors. This review surveys reported substrate phosphorylation site inhibitors and methods that can be applied to the discovery of such inhibitors, including a discussion of the challenges inherent to these screening methods.

Source Name

ACS chemical biology

Publication Date

12-10-2014

Volume

10

Issue

1

Page(s)

175-189

Document Type

Citation

Citation Type

Article

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