Human kinome drug discovery and the emerging importance of atypical allosteric inhibitors

Abstract

Importance of the field: Protein kinases are important targets for drug discovery because they possess critical roles in many human diseases. Several protein kinase inhibitors have entered clinical development with others having already been approved for treating a host of diseases. However, many kinase inhibitors suffer from non-selectivity because they interact with the ATP binding region which has similar structures amongst the protein kinases and this non-selectivity sometimes can cause side effects. As a consequence, there is much interest in developing drugs that inhibit kinases through non-classical mechanisms with the hope of avoiding the side effects of previous kinase drugs.

Areas covered in this review: This review covers emerging information on kinase biology and discusses new approaches to design selective inhibitors that do not compete with ATP.

What the reader will gain: The reader will gain a better understanding of the importance of the field of allosteric inhibitor drug discovery and how this has required the adoption of a new generation of high-throughput screening techniques.

Take home message: Discovery and development of allosteric modulators will result in a family of novel kinase therapies with greater selectivity and more varied ways to control activity of disease causing kinase targets.

Keywords::

• allosteric
• allosterism
• assay
• discovery
• high-throughput screening
• kinase
• kinome
• protein redistribution
• protein translocation

Notes

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