Democratized Discovery of Microsclerodermin F as an Immunophilin Ligand.

While immunophilins are well-recognized therapeutic targets, several members of this family of peptidyl-proline isomerases (PPIases) have yet to be subjected to ligand discovery efforts. In this study, we demonstrate a cost-effective means to identify ligands to the insufficiently investigated two-domain PPIase human Cyclophilin40 (Cyp40). Central to this effort was the use of beads, wherein a confocal nanoscanning (CONA) approach was used to rapidly probe candidates. Here, we describe how one can adapt the physical nature of microsized beads as a means to strategically reduce cost and ultimately make the discovery of small molecule hit and lead compounds more accessible to everyone irrespective of financial status (democratization).