RG3039

RG3039 (PF-06687859) is an orally active, blood-brain barrier-permeable DcpS inhibitor with an IC₅₀ of 4.2 nM against hDcpS. RG3039 inhibits the decapping activity of DcpS and maintains DcpS in a catalytically inactive conformation in the central nervous system and other tissues. RG3039 extends survival and improves function in spinal muscular atrophy mice. RG3039 is applicable to research related to spinal muscular atrophy^[1][2]. In Vitro:RG3039 (1-100 nM) potently inhibits the decapping enzyme activity of purified hDcpS, with an IC₅₀ of 4.2 nM^[1]. In Vivo:RG3039 (20 mg/kg; p.o.; once daily; from P4 to P20) extends the median survival of 2B/2 SMA mice by over 600% to 112 days, and improves their cardiac, motor and neuromuscular functions^[1].
RG3039 (20 mg/kg; p.o.; once daily; postnatal day 11 to postnatal day 20) confers only a very weak survival benefit in 2B/2 SMA mice (median survival time: 23 days)^[1].
RG3039 (3-40 mg/kg; daily; starting from postnatal day 1) hydrochloride potently inhibits DcpS in vivo, and improves survival rate, motor function, synaptic connectivity, neuromuscular junction function and muscle size in severe SMA mice^[2].