Multimodal small-molecule screening for human prion protein binders
Andrew G. Reidenbach, Michael F. Mesleh, Dominick Casalena, Sonia M. Vallabh, Jayme L. Dahlin, Alison Leed, Alix I Chan, Dmitry L. Usanov, Jenna Yehl, Christopher T. Lemke, Arthur J. Campbell, Rishi Shah, Om Kumar Shrestha, Joshua R. Sacher, V.L. Rangel, Jamie A. Moroco, Murugappan Sathappa, Maria Cristina Nonato, Kong T. Nguyen, S. Kirk Wright, David R. Liu, Florence F. Wagner, Virendar K. Kaushik, Douglas S. Auld, Stuart L. Schreiber, Eric Vallabh Minikel
Abstract
> 1 mm), and it could not be advanced further. The exceptionally low hit rate observed here suggests that PrP is a difficult target for small-molecule binders. Whereas orthogonal binder discovery methods could yield high-affinity compounds, non-small-molecule modalities may offer independent paths forward against prion disease.