Fragment-Based Discovery of Novel Potent Sepiapterin Reductase Inhibitors.
Basic Information
ID: ALA4359832
Journal: J Med Chem
Title: Fragment-Based Discovery of Novel Potent Sepiapterin Reductase Inhibitors.
Authors: Alen J, Schade M, Wagener M, Christian F, Nordhoff S, Merla B, Dunkern TR, Bahrenberg G, Ratcliffe P.
Abstract: Genome-wide-association studies in chronic low back pain patients identified sepiapterin reductase as a high interest target for developing new analgesics. Here we used 19F NMR fragment screening for the discovery of novel, ligand-efficient SPR inhibitors. We report the crystal structures of six chemically diverse inhibitors complexed with SPR, identifying relevant interactions and binding modes in the sepiapterin pocket. Exploration of our initial fragment screening hit led to double-digit nanomolar inhibitors of SPR with excellent ligand efficiency.
CiteXplore: 31244106
DOI: 10.1021/acs.jmedchem.9b00218
Patent ID: ┄