RG3039 (PF-06687859) is a potent, orally bioavailable and brain-penetrant inhibitor of the ribonucleic acid scavenger enzyme DcpS with IC50 of 3.4 nM.
RG3039 crosses the blood brain barrier and inhibits the RNA decapping enzyme DcpS in the CNS.
RG3039 showed a dose-dependent increase in survival, weight and motor function in SMA mice, with improved motor neuron somal and neuromuscular junction synaptic innervation and function and increased muscle size.
RG3039 also enhanced survival of conditional SMA mice in which SMN had been genetically restored to motor neurons.
