Branaplam free base
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MedKoo CAT#: 526827

CAS#: 1562338-42-4 (free base)

Description: Branaplam, also known as NVS-SM1 and LMI-070, is a highly potent, selective and orally active small molecule SMN2 splicing modulator as a potential treatment for SMA Type 1 (Spinal Muscular Atrophy) .NVS-SM1 works by increasing the amount of functional SMN protein produced by the “back-up” gene, SMN2, through modifying its splicing.

Chemical Structure

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Branaplam free base
CAS# 1562338-42-4 (free base)
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 526827
Name: Branaplam free base
CAS#: 1562338-42-4 (free base)
Chemical Formula: C22H27N5O2
Exact Mass: 393.22
Molecular Weight: 393.491
Elemental Analysis: C, 67.15; H, 6.92; N, 17.80; O, 8.13

Price and Availability

Size Price Availability Quantity
5mg USD 90 Ready to ship
10mg USD 150 Ready to ship
25mg USD 250 Ready to ship
50mg USD 450 Ready to ship
100mg USD 750 Ready to ship
200mg USD 1250 Ready to ship
500mg USD 2650 Ready to ship
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Related CAS #: 1562338-42-4 (free base)   1562338-39-9 (HCl)   Branaplam mesylate    

Synonym: NVS-SM1; NVS SM1; NVSSM1; LMI-070; LMI070; LMI 070; Branaplam

IUPAC/Chemical Name: 5-(1H-pyrazol-4-yl)-2-[6-[(2,2,6,6-tetramethyl-4-piperidinyl)oxy]-3-pyridazinyl]-phenol

InChi Key: STWTUEAWRAIWJG-UHFFFAOYSA-N

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)

SMILES Code: OC1=CC(C2=CNN=C2)=CC=C1C3=NN=C(OC4CC(C)(C)NC(C)(C)C4)C=C3

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:

Biological target: Branaplam (LMI070) is a highly selective, small-molecule splicing modulators of survival motor neuron‑2 (SMN2) with an EC50 of 0.02 μM.
In vitro activity: In the cellular setting, it was observed that SMN protein levels remained elevated after compound treatment, which and suggests that SMN protein has a long half-life. Branaplam (LMI070; NVS-SM1) treatment induces changes in the levels of 175 genes in human fibroblasts. Reference: Nat Chem Biol. 2015 Jul;11(7):511-7. https://doi.org/10.1038/nchembio.1837
In vivo activity: The C/+ SMA mouse model was employed. After oral administration, NVS-SM1 produced dose-dependent elevations of SMN2-FL transcript and SMN protein in brain and spinal cord (Fig. 2a,b), thus establishing translatability and a pharmacokinetic-pharmacodynamic relationship. Although it showed dose-responsive activity in the C/+ model (Fig. 2a,b), NVS-SM1 exhibited efficacy at lower doses and exposures. NVS-SM1 showed robust activity across disease-relevant induced pluripotent stem cell (iPSc)-derived neurons (Supplementary Fig. 2a,b). It was also demonstrated that the desired transcript response in SMA-type III PBMCs after NVS-SM1 treatment, suggesting that this readout could serve as a peripheral pharmacodynamic marker in the clinic (Supplementary Fig. 2c). A single, 30 mg per kg body weight oral dose of NVS-SM1 resulted in significant (P < 0.05) and durable SMN protein elevation in brain for up to 160 h (Fig. 2c). Reference: Nat Chem Biol. 2015 Jul;11(7):511-7. https://doi.org/10.1038/nchembio.1837

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 3.0 7.62

Preparing Stock Solutions

The following data is based on the product molecular weight 393.49 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
In vitro protocol: 1. Palacino J, Swalley SE, Song C, Cheung AK, Shu L, Zhang X, Van Hoosear M, Shin Y, Chin DN, Keller CG, Beibel M, Renaud NA, Smith TM, Salcius M, Shi X, Hild M, Servais R, Jain M, Deng L, Bullock C, McLellan M, Schuierer S, Murphy L, Blommers MJ, Blaustein C, Berenshteyn F, Lacoste A, Thomas JR, Roma G, Michaud GA, Tseng BS, Porter JA, Myer VE, Tallarico JA, Hamann LG, Curtis D, Fishman MC, Dietrich WF, Dales NA, Sivasankaran R. SMN2 splice modulators enhance U1-pre-mRNA association and rescue SMA mice. Nat Chem Biol. 2015 Jul;11(7):511-7. doi: 10.1038/nchembio.1837. Epub 2015 Jun 1. Erratum in: Nat Chem Biol. 2015 Sep;11(9):741. Erratum in: Nat Chem Biol. 2016 Apr;12(4):304. PMID: 26030728.
In vivo protocol: 1. Palacino J, Swalley SE, Song C, Cheung AK, Shu L, Zhang X, Van Hoosear M, Shin Y, Chin DN, Keller CG, Beibel M, Renaud NA, Smith TM, Salcius M, Shi X, Hild M, Servais R, Jain M, Deng L, Bullock C, McLellan M, Schuierer S, Murphy L, Blommers MJ, Blaustein C, Berenshteyn F, Lacoste A, Thomas JR, Roma G, Michaud GA, Tseng BS, Porter JA, Myer VE, Tallarico JA, Hamann LG, Curtis D, Fishman MC, Dietrich WF, Dales NA, Sivasankaran R. SMN2 splice modulators enhance U1-pre-mRNA association and rescue SMA mice. Nat Chem Biol. 2015 Jul;11(7):511-7. doi: 10.1038/nchembio.1837. Epub 2015 Jun 1. Erratum in: Nat Chem Biol. 2015 Sep;11(9):741. Erratum in: Nat Chem Biol. 2016 Apr;12(4):304. PMID: 26030728. 2. Cheung AK, Hurley B, Kerrigan R, Shu L, Chin DN, Shen Y, O'Brien G, Sung MJ, Hou Y, Axford J, Cody E, Sun R, Fazal A, Fridrich C, Sanchez CC, Tomlinson RC, Jain M, Deng L, Hoffmaster K, Song C, Van Hoosear M, Shin Y, Servais R, Towler C, Hild M, Curtis D, Dietrich WF, Hamann LG, Briner K, Chen KS, Kobayashi D, Sivasankaran R, Dales NA. 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. doi: 10.1021/acs.jmedchem.8b01291. Epub 2018 Dec 13. PMID: 30407821.

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8: Cheung AK, Hurley B, Kerrigan R, Shu L, Chin DN, Shen Y, O'Brien G, Sung MJ, Hou Y, Axford J, Cody E, Sun R, Fazal A, Fridrich C, Sanchez CC, Tomlinson RC, Jain M, Deng L, Hoffmaster K, Song C, Van Hoosear M, Shin Y, Servais R, Towler C, Hild M, Curtis D, Dietrich WF, Hamann LG, Briner K, Chen KS, Kobayashi D, Sivasankaran R, Dales NA. 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. doi: 10.1021/acs.jmedchem.8b01291. Epub 2018 Dec 13. PMID: 30407821.


9: Ottesen EW, Singh NN, Luo D, Kaas B, Gillette BJ, Seo J, Jorgensen HJ, Singh RN. Diverse targets of SMN2-directed splicing-modulating small molecule therapeutics for spinal muscular atrophy. Nucleic Acids Res. 2023 Apr 7:gkad259. doi: 10.1093/nar/gkad259. Epub ahead of print. PMID: 37026480.


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