VP3.15 dihydrobromide is a potent, oral bioavailable and CNS penetrant dual PDE7/GSK-3 inhibitor with IC50 of 1.59 uM (PDE7) and 0.88 uM (GSK-3). VP3.15 increases intracellular cAMP levels in cells. VP3.15 is efficacious in the amelioration of the clinical symptoms in EAE mice. VP3.15 improves in vivo remyelination in mouse and increases both adult mouse and adult human oligodendrocyte progenitor cell (OPC) differentiation, in addition to its immune regulatory action. VP3.15's dual inhibition is synergistic, as increasing intracellular levels of cAMP by cyclic nucleotide PDE inhibition both suppresses the immune response and increases remyelination, and in addition, inhibition of GSK3 limits experimental autoimmune encephalomyelitis in mice.
