Design of a Potent, Selective, and Brain-Penetrant Inhibitor of Wnt-Deactivating Enzyme Notum by Optimization of a Crystallographic Fragment Hit
Nicky J. Willis, William Mahy, James Sipthorp, Yuguang Zhao, Hannah L. Woodward, Benjamin N. Atkinson, Elliott D. Bayle, Fredrik Svensson, Sarah Frew, Fiona Jeganathan, Amy E. Monaghan, Stefano Benvegnù, Sarah Jolly, Luca Vecchia, Reinis R. Ruza, Svend Kjær, Steven Howell, Ambrosius P. Snijders, Magda Bictash, Patricia C. Salinas, Jean‐Paul Vincent, E. Yvonne Jones, Paul J. Whiting, Paul V. Fish
Abstract
to be selective against serine hydrolases, kinases, and drug targets.
Topics & Concepts
Wnt signaling pathwayChemistryEnzymeNeurodegenerationBiochemistryDrug discoveryComputational biologyPharmacologySignal transductionBiologyDiseaseMedicinePathologyWnt/β-catenin signaling in development and cancerCancer-related gene regulationComputational Drug Discovery Methods