Branaplam, identified as LMI070 or NVS-SM1, is distinguished by its potent, selective, and orally bioavailable qualities as an SMN2 splicing modulator, displaying an EC50 of 20 nM. It inhibits the hERG channel with an IC50 of 6.3 μM, enhances full-length SMN protein levels, and improves survival in a severe spinal muscular atrophy (SMA) mouse model[1].[2].
体内研究
Branaplam induces dose-dependent increases in SMN2-FL transcript and SMN protein in both brain and spinal cord at doses of 3, 10, and 30 mg/kg orally[1].
With a clearance rate (CL) of 25 mL/min/kg and an area under the curve (AUC) of 3.03 μM·h when administered at 1 mg/kg intravenously (IV) and 3 mg/kg orally (PO)[2].
A single oral dose of 30 mg/kg of Branaplam results in a significant and lasting elevation of SMN protein in the brain for up to 160 hours in C/+ mice[1].
Lastly, oral administration of Branaplam at doses ranging from 0.03 to 3 mg/kg leads to improvements in body weight and extends the lifespan of SMNΔ7 mice[1].
体外研究
Branaplam treatment alters the expression of 175 genes in human fibroblasts[1].
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