Branaplam

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]

Branaplam

Clinical data
Other names	LMI070; 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	1562338-42-4
PubChem CID	89971189
ChemSpider	34980709
UNII	P12R69543A
Chemical and physical data
Formula	C22H27N5O2
Molar mass	393.491 g·mol^−1
3D model (JSmol)	Interactive image
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

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]

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.