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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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500mg |
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Purity: ≥98%
LMI-070 (Branaplam; NVS-SM1) is a potent, orally bioactive, small-molecule enhancer of SMN2 (survival of motor neuron-2) splicing that elevates full-length SMN protein and extends survival in a severe SMA mouse model. The transient double-strand RNA structure created by the U1 small nuclear ribonucleic protein (snRNP) complex and SMN2 pre-mRNA is stabilized as the molecular mechanism of action. Separate from constitutive recognition, the binding affinity of U1 snRNP to the 5' splice site is enhanced in a sequence-specific manner. This novel mechanism highlights the viability of sequence-selective splice modulation mediated by small molecules and the possibility of applying this tactic to other splicing disorders.
Targets |
SMN ( IC50 = 20 nM ); hERG ( EC50 = 6.3 μM )
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ln Vitro |
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ln Vivo |
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Animal Protocol |
C/+ SMA mouse model
3, 10, 30 mg/kg Oral |
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References |
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Molecular Formula |
C22H27N5O2
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Molecular Weight |
393.49
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Exact Mass |
393.22
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Elemental Analysis |
C, 67.15; H, 6.92; N, 17.80; O, 8.13
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CAS # |
1562338-42-4
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Related CAS # |
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Appearance |
Solid powder
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SMILES |
CC1(CC(CC(N1)(C)C)OC2=NN=C(C=C2)C3=C(C=C(C=C3)C4=CNN=C4)O)C
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InChi Key |
STWTUEAWRAIWJG-UHFFFAOYSA-N
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InChi Code |
InChI=1S/C22H27N5O2/c1-21(2)10-16(11-22(3,4)27-21)29-20-8-7-18(25-26-20)17-6-5-14(9-19(17)28)15-12-23-24-13-15/h5-9,12-13,16,27-28H,10-11H2,1-4H3,(H,23,24)
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Chemical Name |
5-(1H-pyrazol-4-yl)-2-[6-(2,2,6,6-tetramethylpiperidin-4-yl)oxypyridazin-3-yl]phenol
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Synonyms |
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HS Tariff Code |
2934.99.9001
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Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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Solubility (In Vitro) |
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Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (2.54 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 0.71 mg/mL (1.80 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 7.1 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 0.71 mg/mL (1.80 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: ≥ 0.57 mg/mL (1.45 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 5: 1% DMSO 99% Saline |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 2.5414 mL | 12.7068 mL | 25.4136 mL | |
5 mM | 0.5083 mL | 2.5414 mL | 5.0827 mL | |
10 mM | 0.2541 mL | 1.2707 mL | 2.5414 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT05111249 | Completed | Drug: Branaplam Drug: Placebo |
Early Manifest Huntington Disease |
Novartis Pharmaceuticals | December 8, 2021 | Phase 2 |
NCT02268552 | Completed | Drug: branaplam | Spinal Muscular Atrophy | Novartis Pharmaceuticals | April 2, 2015 | Phase 1 Phase 2 |
NCT05330286 | Terminated | Drug: LMI070 | Healthy Volunteers | Novartis Pharmaceuticals | April 13, 2022 | Phase 1 |