Hinge Binder Scaffold Hopping Identifies Potent Calcium/Calmodulin-Dependent Protein Kinase Kinase 2 (CAMKK2) Inhibitor Chemotypes
Benjamin J. Eduful, Sean O’Byrne, Louisa Temme, Christopher R. M. Asquith, Yi Liang, Alfredo Picado, Joseph Pilotte, Mohammad Anwar Hossain, Carrow I. Wells, William J. Zuercher, Carolina Moura Costa Catta‐Preta, Priscila Zonzini Ramos, André de S. Santiago, Rafael M. Couñago, Christopher G. Langendorf, Kévin Nay, Jonathan S. Oakhill, Thomas L. Pulliam, Chenchu Lin, Dominik Awad, Timothy M. Willson, Daniel E. Frigo, John W. Scott, David H. Drewry
Abstract
had improved selectivity for CAMKK2 across the kinome. Our systematic survey of hinge-binding chemotypes identified several potent and selective inhibitors of CAMKK2 to serve as starting points for medicinal chemistry programs.
Topics & Concepts
ChemistryProtein kinase AKinaseBiochemistryKinomeSerineEnzymeStereochemistryCombinatorial chemistryBiophysicsBiologyHistone Deacetylase Inhibitors ResearchQuinazolinone synthesis and applicationsMetabolism, Diabetes, and Cancer