Skora, Lukasz and Jahnke, Wolfgang (2017) 19F-NMR-based dual-site reporter assay for the discovery and distinction of catalytic and allosteric kinase inhibitors. ACS medicinal chemistry letters, 8. pp. 632-635.

Abstract

In modern kinase drug discovery, allosteric inhibitors have become a focus of attention due to their potential selectivity, but such compounds are difficult to identify. Here we describe an NMR-based competition assay using 19F-containing reporter molecules, which allows for rapid identification and discrimination between ATP-competitive and allosteric kinase inhibitors. We illustrate the principle of such a dual-site competition assay with the example of catalytic and allosteric ABL1 kinase inhibitors. The assay can also be used to identify and characterize mixed binding modes of well-known drugs, as shown for crizotinib and fingolimod.

Item Type:	Article
Date Deposited:	06 Mar 2018 00:45
Last Modified:	06 Mar 2018 00:45
URI:	https://oak.novartis.com/id/eprint/31937