Branaplam (LMI070; NVS-SM1) 是一种口服有效和选择性的 SMN2 拼接调节剂，对 SMN 的 EC₅₀ 为 20 nM。Branaplam 抑制 hERG，IC₅₀ 为 6.3 μM。Branaplam 在严重的脊髓性肌萎缩症 (SMA) 小鼠模型中可提高全长 SMN 蛋白并延长其生存期。

Branaplam (LMI070; NVS-SM1) is a highly potent, selective and orally active survival motor neuron-2 (SMN2) splicing modulator with an EC 50 of 20 nM for SMN. Branaplam inhibits human-ether-a-go-go-related gene (hERG) with an IC 50 of 6.3 μM. Branaplam elevates full-length SMN protein and extends survival in a severe spinal muscular atrophy (SMA) mouse model.

Solid

IC50: 20 nM (SMN)
EC50: 6.3 μM (hERG)

Branaplam (LMI070; NVS-SM1) treatment induces changes in the levels of 175 genes in human fibroblasts.
has not independently confirmed the accuracy of these methods. They are for reference only.

Branaplam (LMI070; NVS-SM1; 3, 10, 30 mg/kg; oral) produces dose-dependent elevations of SMN2-FL transcript and SMN protein in brain and spinal cord.
Branaplam (1 mg/kg of IV; 3 mg/kg of PO) has a CL of 25 mL/min/kg and an AUC of 3.03 μM?h.
A single Branaplam (oral; 30 mg/kg) results in significant and durable SMN protein elevation in brain for up to 160 hours in C/+ mice.
Branaplam (oral; 0.03, 0.1, 0.3, 1, 3 mg/kg) improves body weight and extendes lifespan in n SMNΔ7 mice.
has not independently confirmed the accuracy of these methods. They are for reference only.

Room temperature in continental US; may vary elsewhere.

4°C, sealed storage, away from moistur In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)

[1]. Palacino J, et al. SMN2 splice modulators enhance U1-pre-mRNA association and rescue SMA mice. Nat Chem Biol. 2015 Jul;11(7):511-517.
[2]. Cheung AK, et al. Discovery of Small Molecule Splicing Modulators of Survival Motor Neuron-2 (SMN2) for the Treatment of Spinal Muscular Atrophy (SMA). J Med Chem. 2018 Dec 27;61(24):11021-11036.

In Vitro: DMSO : 5 mg/mL (12.71 mM; ultrasonic and warming and heat to 80°C)配制储备液