Branaplam (LMI070)
(Synonyms: LMI070; NVS-SM1) 目录号 : GC32702
An SMN2 splice modulator
Cas No.:1562338-42-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
LMI070 is an SMN2 splice modulator.1 It selectively enhances SMN2 splicing by stabilizing the complex formed by the U1 small nuclear ribonucleic protein (snRNP) and SMN2 pre-mRNA. LMI070 (3-30 mg/kg) increases the expression of the full-length SMN2 trancript and, at doses ranging from 0.3 to 30 mg/kg, increases SMN protein levels in the brain and spinal cord in the C/+ mouse model of spinal muscular atrophy (SMA).1,2 It also increases survival of SMNΔ7 mice, a model of severe SMA, when administered at doses of 1 and 3 mg/kg.1
1.Palacino, J., Swalley, S.E., Song, C., et al.SMN2 splice modulators enhance U1-pre-mRNA association and rescue SMA miceNat. Chem. Biol.11(7)511-517(2015) 2.Cheung, A.K., Hurley, B., Kerrigan, R., 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.61(24)11021-11036(2018)
| Cas No. | 1562338-42-4 | SDF | |
| 别名 | LMI070; NVS-SM1 | ||
| Canonical SMILES | OC1=CC(C2=CNN=C2)=CC=C1C3=CC=C(OC4CC(C)(C)NC(C)(C)C4)N=N3 | ||
| 分子式 | C22H27N5O2 | 分子量 | 393.48 |
| 溶解度 | DMSO : 6.12 mg/mL (15.55 mM) | 储存条件 | Store at -20°C |
| General tips | 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 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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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 |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
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.PMID:30407821DOI:10.1021/acs.jmedchem.8b01291
Spinal muscular atrophy (SMA), a rare neuromuscular disorder, is the leading genetic cause of death in infants and toddlers. SMA is caused by the deletion or a loss of function mutation of the survival motor neuron 1 (SMN1) gene. In humans, a second closely related gene SMN2 exists; however it codes for a less stable SMN protein. In recent years, significant progress has been made toward disease modifying treatments for SMA by modulating SMN2 pre-mRNA splicing. Herein, we describe the discovery of LMI070/Branaplam, a small molecule that stabilizes the interaction between the spliceosome and SMN2 pre-mRNA. Branaplam (1) originated from a high-throughput phenotypic screening hit, pyridazine 2, and evolved via multiparameter lead optimization. In a severe mouse SMA model, Branaplam treatment increased full-length SMN RNA and protein levels, and extended survival. Currently, Branaplam is in clinical studies for SMA.