Branaplam: Difference between revisions

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{{Infobox drug
{{Infobox drug
| IUPAC_name = (6''E'')-3-(1''H''-pyrazol-4-yl)-6-[3-(2,2,6,6-tetramethylpiperidin-4-yl)oxy-1''H''-pyridazin-6-ylidene]cyclohexa-2,4-dien-1-one
| IUPAC_name = (6''E'')-3-(1''H''-Pyrazol-4-yl)-6-[3-(2,2,6,6-tetramethylpiperidin-4-yl)oxy-1''H''-pyridazin-6-ylidene]cyclohexa-2,4-dien-1-one
| image = Branaplam skeletal.svg
| image = Branaplam skeletal.svg
| alt =
| alt =
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<!-- Chemical and physical data -->
<!-- Chemical and physical data -->
| C=22 | H=27 | N=5 | O=2
| C=22 | H=27 | N=5 | O=2
| molecular_weight = 393.491 g/mol
| smiles = CC1(CC(CC(N1)(C)C)Oc2ccc(nn2)c3ccc(cc3O)c4c[nH]nc4)C
| smiles = CC1(CC(CC(N1)(C)C)Oc2ccc(nn2)c3ccc(cc3O)c4c[nH]nc4)C
| StdInChI=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+
| StdInChI=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+
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}}
}}


'''Branaplam''', also known as '''LMI070''' and '''NVS-SM1''', is a highly potent, selective and orally active [[small molecule]] [[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|''SMN2'' gene]] through [[alternative splicing|modifying its splicing pattern]].<ref>{{cite journal| doi=10.1038/nchembio.1837| pmid=26030728| title=SMN2 splice modulators enhance U1–pre-mRNA association and rescue SMA mice| journal=Nature Chemical Biology| volume=11| issue=7| pages=511| year=2015| last1=Palacino| first1=James| last2=Swalley| first2=Susanne E| last3=Song| first3=Cheng| last4=Cheung| first4=Atwood K| last5=Shu| first5=Lei| last6=Zhang| first6=Xiaolu| last7=Van Hoosear| first7=Mailin| last8=Shin| first8=Youngah| last9=Chin| first9=Donovan N| last10=Keller| first10=Caroline Gubser| last11=Beibel| first11=Martin| last12=Renaud| first12=Nicole A| last13=Smith| first13=Thomas M| last14=Salcius| first14=Michael| last15=Shi| first15=Xiaoying| last16=Hild| first16=Marc| last17=Servais| first17=Rebecca| last18=Jain| first18=Monish| last19=Deng| first19=Lin| last20=Bullock| first20=Caroline| last21=McLellan| first21=Michael| last22=Schuierer| first22=Sven| last23=Murphy| first23=Leo| last24=Blommers| first24=Marcel J J| last25=Blaustein| first25=Cecile| last26=Berenshteyn| first26=Frada| last27=Lacoste| first27=Arnaud| last28=Thomas| first28=Jason R| last29=Roma| first29=Guglielmo| last30=Michaud| first30=Gregory A| display-authors=29}}</ref><ref name=smanewstoday>{{cite web | url=https://smanewstoday.com/lmi070-novartis/ | title=LMI070 | publisher=SMA News Today | accessdate=2017-03-10}}</ref>
'''Branaplam''' (development codes '''LMI070''' and '''NVS-SM1''') is a potent, selective and orally active [[small molecule]] [[experimental drug]] being developed by [[Novartis]] to treat [[spinal muscular atrophy]] (SMA). It is a [[pyridazine]] [[derivative (chemistry)|derivative]] that works by increasing the amount of functional [[survival of motor neuron]] protein produced by the [[SMN2|''SMN2'' gene]] through [[alternative splicing|modifying its splicing pattern]].<ref>{{cite journal| doi=10.1038/nchembio.1837| pmid=26030728| title=SMN2 splice modulators enhance U1–pre-mRNA association and rescue SMA mice| journal=Nature Chemical Biology| volume=11| issue=7| pages=511| year=2015| last1=Palacino| first1=James| last2=Swalley| first2=Susanne E| last3=Song| first3=Cheng| last4=Cheung| first4=Atwood K| last5=Shu| first5=Lei| last6=Zhang| first6=Xiaolu| last7=Van Hoosear| first7=Mailin| last8=Shin| first8=Youngah| last9=Chin| first9=Donovan N| last10=Keller| first10=Caroline Gubser| last11=Beibel| first11=Martin| last12=Renaud| first12=Nicole A| last13=Smith| first13=Thomas M| last14=Salcius| first14=Michael| last15=Shi| first15=Xiaoying| last16=Hild| first16=Marc| last17=Servais| first17=Rebecca| last18=Jain| first18=Monish| last19=Deng| first19=Lin| last20=Bullock| first20=Caroline| last21=McLellan| first21=Michael| last22=Schuierer| first22=Sven| last23=Murphy| first23=Leo| last24=Blommers| first24=Marcel J J| last25=Blaustein| first25=Cecile| last26=Berenshteyn| first26=Frada| last27=Lacoste| first27=Arnaud| last28=Thomas| first28=Jason R| last29=Roma| first29=Guglielmo| last30=Michaud| first30=Gregory A| display-authors=29}}</ref><ref name=smanewstoday>{{cite web | url=https://smanewstoday.com/lmi070-novartis/ | title=LMI070 | publisher=SMA News Today | accessdate=2017-03-10}}</ref>


{{As of|2017|03}}, branaplam is in a phase-II [[clinical trial]] in children with SMA type 1.<ref>{{cite web| url=https://clinicaltrials.gov/ct2/show/NCT02268552 |title=An Open Label Study of LMI070 in Type 1 Spinal Muscular Atrophy (SMA) | publisher=[[ClinicalTrials.gov]] | accessdate=2017-03-10}}</ref><ref>{{cite web | url=http://www.curesma.org/news/novartis-branaplam-update.html | title=Novartis Releases Update on LMI070 (Branaplam) Clinical Trial | publisher = CureSMA | date = 2017-09-20 | accessdate=2017-10-07 }}</ref>
{{As of|2017|03}}, branaplam is in a phase-II [[clinical trial]] in children with SMA type 1.<ref>{{cite web| url=https://clinicaltrials.gov/ct2/show/NCT02268552 |title=An Open Label Study of LMI070 in Type 1 Spinal Muscular Atrophy (SMA) | publisher=[[ClinicalTrials.gov]] | accessdate=2017-03-10}}</ref><ref>{{cite web | url=http://www.curesma.org/news/novartis-branaplam-update.html | title=Novartis Releases Update on LMI070 (Branaplam) Clinical Trial | publisher = CureSMA | date = 2017-09-20 | accessdate=2017-10-07 }}</ref>
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[[Category:Experimental drugs]]
[[Category:Experimental drugs]]
[[Category:Novartis]]
[[Category:Novartis]]
[[Category:Novartis brands]]
[[Category:Pyrazoles]]
[[Category:Piperidines]]



{{drug-stub}}
{{drug-stub}}

Revision as of 18:22, 12 July 2019

Branaplam
Clinical data
Other namesLMI070; NVS-SM1
Identifiers
  • (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
Chemical and physical data
FormulaC22H27N5O2
Molar mass393.491 g·mol−1
3D model (JSmol)
  • CC1(CC(CC(N1)(C)C)Oc2ccc(nn2)c3ccc(cc3O)c4c[nH]nc4)C
  • 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 a potent, selective and orally active small molecule 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 March 2017, branaplam is in a phase-II clinical trial in children with SMA type 1.[3][4]

Keto-enol tautomerism of branaplam

References

  1. ^ Palacino, James; Swalley, Susanne E; Song, Cheng; Cheung, Atwood K; Shu, Lei; Zhang, Xiaolu; Van Hoosear, Mailin; Shin, Youngah; Chin, Donovan N; Keller, Caroline Gubser; Beibel, Martin; Renaud, Nicole A; Smith, Thomas M; Salcius, Michael; Shi, Xiaoying; Hild, Marc; Servais, Rebecca; Jain, Monish; Deng, Lin; Bullock, Caroline; McLellan, Michael; Schuierer, Sven; Murphy, Leo; Blommers, Marcel J J; Blaustein, Cecile; Berenshteyn, Frada; Lacoste, Arnaud; Thomas, Jason R; Roma, Guglielmo; et al. (2015). "SMN2 splice modulators enhance U1–pre-mRNA association and rescue SMA mice". Nature Chemical Biology. 11 (7): 511. 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. Retrieved 2017-10-07.
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