RG3039 hydrochloride

RG3039 hydrochloride is an orally active DcpS inhibitor capable of crossing the blood-brain barrier, with an IC50 of 4.2 nM for hDcpS. It inhibits the decapping activity of DcpS, maintaining the enzyme in a non-catalytic conformation within the central nervous system and other tissues. RG3039 hydrochloride extends survival and improves functionality in mouse models of spinal muscular atrophy, making it useful for research related to this condition.

RG3039 (1-100 nM) is a potent inhibitor of purified hDcpS decapping enzyme activity, with an IC₅₀ of 4.2 nM.

RG3039 hydrochloride, administered at 20 mg/kg via oral gavage once daily from postnatal day 4 to P20, extends the median survival of SMNΔ7 (2B/2) SMA mice by over 600% to 112 days, enhancing cardiac, motor, and neuromuscular functions. However, when given from postnatal day 11 to 20 at the same dosage, it provides only minimal survival benefits, with a median survival of 23 days. Additionally, RG3039 hydrochloride, administered daily at doses ranging from 3 to 40 mg/kg starting from postnatal day 1, substantially improves survival, motor function, synaptic connectivity, neuromuscular junction function, and muscle size in severe SMA mice by effectively inhibiting DcpS in vivo.