Fragments vs Notum, three ways
The Wnt signaling pathway has been implicated in multiple diseases, from Alzheimer’s to cancer to osteoporosis. To be able to bind receptors, Wnt proteins must be post-translationally modified with a palmitoleate group. The carboxylesterase Notum removes this group, shutting of signaling. Thus, inhibitors of Notum could maintain Wnt activity. In two J. Med. Chem. papers, E. Yvonne Jones (University of Oxford), Paul Fish (University College London), and collaborators describe three series of inhibitors derived from fragments. Читать дальше...