Branaplam

Branaplam
Clinical data
Other namesLMI070; NVS-SM1
Identifiers
IUPAC name
  • (6E)-3-(1H-Pyrazol-4-yl)-6-[3-(2,2,6,6-tetramethylpiperidin-4-yl)oxy-1H-pyridazin-6-ylidene]cyclohexa-2,4-dien-1-one
CAS Number
PubChem CID
ChemSpider
UNII
KEGG
Chemical and physical data
FormulaC22H27N5O2
Molar mass393.491 g·mol−1
3D model (JSmol)
SMILES
  • CC1(CC(CC(N1)(C)C)Oc2ccc(nn2)c3ccc(cc3O)c4c[nH]nc4)C
InChI
  • 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/h5-9,12-13,16,25,27H,10-11H2,1-4H3,(H,23,24)/b18-17+
  • Key:YIFFDXMJVNKGBL-ISLYRVAYSA-N

  • 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)
  • Key:STWTUEAWRAIWJG-UHFFFAOYSA-N

Branaplam (development codes LMI070 and NVS-SM1) is an experimental drug being developed by Novartis to treat spinal muscular atrophy (SMA). It is a pyridazine derivative that works by increasing the amount of functional survival of motor neuron protein produced by the SMN2 gene through modifying its splicing pattern.[1][2]

As of July 2019, branaplam is in a phase-II clinical trial in children with SMA type 1.[3][4][5]

In October 2020, Novartis stated that the running trials for SMA showed that branaplam lowers the level of huntingtin protein as well. Lowering huntingtin protein is one of the major approaches researched by different companies to cure Huntington's disease. U.S. Food and Drug Administration granted an orphan drug status to branaplam for treatment of Huntington’s disease, and Novartis announced that they will set up trials for HD patients in 2021.[6] In December 2021, Branaplam garnered Fast Track breakthrough designation by the FDA towards a Phase IIb study in adult patients with early-stage HD manifestaion.[7][8]

Keto-enol tautomerism of branaplam

References

  1. ↑ Palacino J, Swalley SE, Song C, Cheung AK, Shu L, Zhang X, et al. (July 2015). "SMN2 splice modulators enhance U1-pre-mRNA association and rescue SMA mice". Nature Chemical Biology. 11 (7): 511–7. doi:10.1038/nchembio.1837. PMID 26030728.
  2. ↑ "LMI070". SMA News Today. Retrieved 2017-03-10.
  3. ↑ "An Open Label Study of LMI070 in Type 1 Spinal Muscular Atrophy (SMA)". ClinicalTrials.gov. Retrieved 2017-03-10.
  4. ↑ "Novartis Releases Update on LMI070 (Branaplam) Clinical Trial". CureSMA. 2017-09-20. Archived from the original on 2017-11-25. Retrieved 2017-10-07.
  5. ↑ "| Novartis announced that enrollment for the ongoing clinical trial of branaplan is now closed". 20 May 2019. Retrieved 2019-07-12.
  6. ↑ "Novartis receives US Food and Drug Administration (FDA) Orphan Drug Designation for branaplam (LMI070) in Huntington's disease (HD)". novartis.com. Retrieved 2020-10-24.
  7. ↑ MS, Marisa Wexler. "Branaplam for Huntington's on FDA's Fast Track; Phase 2 Trial Enrolling".
  8. ↑ "Novartis receives FDA Fast Track designation for branaplam (LMI070) for the treatment of Huntington's Disease". Novartis.
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