Abstractí¬Cyclophilin A (CypA) is a ubiquitous cellular enzyme playing critical roles in many biological processes, and its inhibitor
has been reported to have potential immunosuppressive activity. In this work, we reported a novel quinoxaline derivative, 2,3-di(furan-
2-yl)-6-(3-N,N-diethylcarbamoyl-piperidino)carbonylamino quinoxaline (DC838, 3), which was confirmed to be a potent inhibitor
against human CypA. By using the surface plasmon resonance (SPR) and fluorescence titration techniques, the kinetic analysis
of CypA/DC838 interaction was quantitatively performed. CypA peptidyl prolyl cisĘCtrans isomerase (PPIase) activity inhibition
assay showed that DC838 demonstrated highly CypA PPIase inhibitory activity. In vivo assay results showed that DC838 could
inhibit mouse spleen cell proliferation induced by concanavalin A (Con A). Molecular docking simulation further elucidated the
specific DC838 binding to CypA at the atomic level. The current work should provide useful information in the discovery of immunosuppressor
based on CypA inhibitor.