S-8660

S-8660 is an orally active, selective inhibitor of dihydroorotate dehydrogenase (DHODH). As an antiproliferative prodrug and an analog of Brequinar (HY-108325), S-8660 exhibits immunosuppressive activity. Its effect on prolonging cardiac allograft survival is enhanced when used in combination with Cyclosporin A (HY-B0579). S-8660 can be used in studies of cardiac transplant rejection^[1]. In Vitro:S-8660 selectively inhibits mitochondrial dihydroorotate dehydrogenase, disrupting de novo pyrimidine synthesis in a cell-free biochemical system^[1].
S-8660 suppresses human mixed-lymphocyte responses in vitro^[1]. In Vivo:S-8660 (5-20 mg/kg; p.o.; once daily; starting 2 days pre-transplant for up to 30 days post-transplant) prolongs cardiac allograft survival in rats in a dose-dependent fashion, with a tapered dose regimen achieving a median survival time of 32 days^[1].