A new "angle" on kinase inhibitor design: Prioritizing amphosteric activity above kinase inhibition

Mol Cell Oncol. 2015 Feb 25;2(2):e975641. doi: 10.4161/23723556.2014.975641. eCollection 2015 Apr-Jun.

Abstract

The MYCN oncoprotein has remained an elusive target for decades. We recently reported a new class of kinase inhibitors designed to disrupt the conformation of Aurora kinase A enough to block its kinase-independent interaction with MYCN, resulting in potent degradation of MYCN. These studies provide proof-of-principle for a new method of targeting enzyme activity-independent functions of kinases and other enzymes.

Keywords: AURKA; Aurora kinase A; MYC; MYCN; cancer; kinase inhibition.