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RG3039
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RG3039
CAS No. : 1005504-62-0
MCE 站:RG3039
产品活性:RG3039 (PF-06687859) 是具有口服活性,可渗透大脑的 DcpS 抑制剂, IC50 值为 0.069 nM。
研究领域:Others
作用靶点:Others
In Vitro: RG3039 is a dibasic lipophilic molecule that is predicted to accumulate in lysosomes. In motor neurons, RG3039 significantly increases both the average number of cells with gems and average number of gems per cell, which is used as an indirect measure of SMN levels.
In Vivo: RG3039 can extend survival and improve function in two SMA mouse models of varying disease severity (Taiwanese 5058 Hemi and 2B/? SMA mice), and positively impacts neuromuscular pathologies. In 2B/? SMA mice, RG3039 provides a >600% survival benefit (median 18 days to >112 days) when dosing began at P4, highlighting the importance of early intervention. RG3039 distributes to central nervous system tissues where it robustly inhibits DcpS enzyme activity, but minimally activates SMN expression or the assembly of small nuclear ribonucleoproteins. RG3039 treated SMA mice shows a dose-dependent increase in survival, weight and motor function and it is associated with improved motor neuron somal and neuromuscular junction synaptic innervation and function and increased muscle size. RG3039 also enhances survival of conditional SMA mice in which SMN has been genetically restored to motor neurons.
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热门标签:PF-06687859