RG3039 hydrochloride

RG3039 hydrochloride is an orally active, blood-brain barrier-permeable DcpS inhibitor with an IC₅₀ of 4.2 nM against hDcpS. RG3039 hydrochloride inhibits the decapping activity of DcpS and maintains DcpS in a catalytically inactive conformation in the central nervous system and other tissues. RG3039 hydrochloride extends survival and improves function in spinal muscular atrophy mice. RG3039 hydrochloride is applicable to research related to spinal muscular atrophy ^{[1] [2]}.

In Vivo, RG3039 (20 mg/kg; p.o.; once daily; from P4 to P20) hydrochloride 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) hydrochloride confers only a very weak survival benefit in 2B/2 SMA mice (median survival time: 23 days)^[1]. RG3039 hydrochloride (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].

In Vitro, RG3039 (1-100 nM) potently hydrochloride inhibits the decapping enzyme activity of purified hDcpS, with an IC₅₀ of 4.2 nM^[1].

References:
[1]. Gogliotti RG, et al. The DcpS inhibitor RG3039 improves survival, function and motor unit pathologies in two SMA mouse models. Hum Mol Genet. 2013;22(20):4084-4101.
[2]. Van Meerbeke JP, et al. The DcpS inhibitor RG3039 improves motor function in SMA mice. Hum Mol Genet. 2013;22(20):4074-4083.