Branaplam(Synonyms: LMI070; NVS-SM1)

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Branaplam (Synonyms: LMI070; NVS-SM1) 纯度: 99.78%

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(Synonyms: LMI070; NVS-SM1)

Branaplam Chemical Structure

CAS No. : 1562338-42-4

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生物活性

Branaplam (LMI070; NVS-SM1) is a highly potent, selective and orally active survival motor neuron-2 (SMN2) splicing modulator with an EC50 of 20 nM for SMN. Branaplam inhibits human-ether-a-go-go-related gene (hERG) with an IC50 of 6.3 μM. Branaplam elevates full-length SMN protein and extends survival in a severe spinal muscular atrophy (SMA) mouse model[1][2].

IC50 & Target

IC50: 20 nM (SMN)[1]
EC50: 6.3 μM (hERG)[2]
体外研究
(In Vitro)

Branaplam (LMI070; NVS-SM1) treatment induces changes in the levels of 175 genes in human fibroblasts[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究
(In Vivo)

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[1].
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[2].
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[1].
Branaplam (oral; 0.03, 0.1, 0.3, 1, 3 mg/kg) improves body weight and extendes lifespan in n SMNΔ7 mice[1].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: C/+ SMA mouse model[1]
Dosage: 3, 10, 30 mg/kg
Administration: Oral
Result: Produced dose-dependent elevations of SMN2-FL transcript and SMN protein in brain and spinal cord.
Animal Model: Male Sprague-Dawley rat[2]
Dosage: 1 mg/kg (IV);3 mg/kg (PO) (Pharmacokinetic Analysis)
Administration: IV or PO
Result: Had a CL of 25 mL/min/kg and an AUC of 3.03 μM•h.

Clinical Trial

分子量

393.48

Formula

C22H27N5O2
CAS 号

1562338-42-4
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式

4°C, sealed storage, away from moisture

*In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
溶解性数据
In Vitro: 

DMSO : 6.12 mg/mL (15.55 mM; Need ultrasonic and warming)

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 2.5414 mL 12.7071 mL 25.4143 mL
5 mM 0.5083 mL 2.5414 mL 5.0829 mL
10 mM 0.2541 mL 1.2707 mL 2.5414 mL

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

  • 1.

    请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: ≥ 1 mg/mL (2.54 mM); Clear solution

    此方案可获得 ≥ 1 mg/mL (2.54 mM，饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例，取 100 μL 10.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

    将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

  • 2.

    请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

    Solubility: ≥ 0.71 mg/mL (1.80 mM); Clear solution

    此方案可获得 ≥ 0.71 mg/mL (1.80 mM，饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例，取 100 μL 7.1 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

    将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
  • 3.

    请依序添加每种溶剂： 10% DMSO    90% corn oil

    Solubility: ≥ 0.71 mg/mL (1.80 mM); Clear solution

    此方案可获得 ≥ 0.71 mg/mL (1.80 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

    以 1 mL 工作液为例，取 100 μL 7.1 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

  • 4.

    请依序添加每种溶剂： 5% DMSO    40% PEG300    5% Tween-80    50% saline

    Solubility: ≥ 0.57 mg/mL (1.45 mM); Clear solution

  • 5.

    请依序添加每种溶剂： 1% DMSO    99% saline

    Solubility: 0.12 mg/mL (0.30 mM); Suspended solution; Need ultrasonic

*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献

  • [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.

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