Découverte d'un puissant inhibiteur de BTK avec un nouveau mode de liaison en utilisant des sélections parallèles avec une bibliothèque chimique encodée dans l'ADN.
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.
