January 5, 2017

Discovery of a potent BTK inhibitor with a novel binding mode using parallel selections with a DNA-encoded chemical library.

2017 Jan. 5|Chembiochem.|Discovery of a potent BTK inhibitor with a novel binding mode using parallel selections with a DNA-encoded chemical library.

We have identified and characterized novel potent inhibitors of Bruton’s tyrosine kinase (BTK) from a single DNA encoded library of over 110 million compounds using multiple parallel selection conditions…Analysis of the co-crystal structure of the most potent compound demonstrates a novel binding mode that reveals a new pocket in BTK. Our results demonstrate that profile-based selection strategies form the basis of a new methodology to rapidly identify small molecule inhibitors with novel binding modes to clinically relevant targets using DNA-encoded libraries.

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