Discovering Potent Small Molecule Inhibitors of Cyclophilin A Using de Novo Drug Design Approach

Abstract: This work describes an integrated approach of de novo
drug design, chemical synthesis, and bioassay for quick identification
of a series of novel small molecule cyclophilin A (CypA)
inhibitors (1-3). The activities of the two most potent CypA
inhibitors (3h and 3i) are 2.59 and 1.52 nM, respectively, which
are about 16 and 27 times more potent than that of cyclosporin A.
This study clearly demonstrates the power of our de novo drug
design strategy and the related program LigBuilder 2.0 in drug