nusinersen   Click here for help

GtoPdb Ligand ID: 9416

Synonyms: ASO-10-27 | BIIB-058 | BIIB058 | Ionis-SMNrx | ISIS 396443 | ISIS SMNRx | ISIS-SMNRx | ISIS396443 | Spinraza®
Approved drug
nusinersen is an approved drug (FDA (2016), EMA (2017))
Compound class: Nucleic acid
Comment: Nusinersen (ISIS 396443) is an antisense oligo(ribo)nucleotide (ASO) which induces survival motor neuron (SMN) protein expression from SMN2 genes with the exon 7-skipping mutation [7].
Nusinersen was initially available for use as a designated orphan drug (by the US FDA and EMA), and was the first drug to be fully approved for the treatment of spinal muscular atrophy (SMA).

The sequence contains 2'-O-(2-methoxyethyl) (2'-MOE)-oligoribonucleotides to reduce nuclease degradation and enhance binding affinity towards the complementary RNA. The full sequence is [2'-O-(2-methoxyethyl)](3'-5')(P-thio)(mU-mC-A-mC-mU-mU-mU-mC-A-mU-A-A-mU-G-mC-mU-G-G) as detailed in the INN record for the agent.
The sequence for nusinersen is claimed in patent WO2010148249A1 as SEQ ID NO: 1 [1].
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 161
Hydrogen bond donors 23
Rotatable bonds 176
Topological polar surface area 3144.17
Molecular weight 7122.28
XLogP -19.23
No. Lipinski's rules broken 3
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES COCCOC1C(OP(=O)(OCC2OC(C(C2OP(=O)(OCC2OC(C(C2OP(=O)(OCC2OC(C(C2OP(=O)(OCC2OC(C(C2OP(=O)(OCC2OC(C(C2OP(=O)(OCC2OC(C(C2OP(=O)(OCC2OC(C(C2OP(=O)(OCC2OC(C(C2OP(=O)(OCC2OC(C(C2O)OCCOC)n2cnc3c2nc(N)[nH]c3=O)S)OCCOC)n2cnc3c2nc(N)[nH]c3=O)S)OCCOC)n2cc(C)c(=O)[nH]c2=O)S)OCCOC)n2cc(C)c(nc2=O)N)S)OCCOC)n2cnc3c2nc(N)[nH]c3=O)S)OCCOC)n2cc(C)c(=O)[nH]c2=O)S)OCCOC)n2cnc3c2ncnc3N)S)OCCOC)n2cnc3c2ncnc3N)S)OCCOC)n2cc(C)c(=O)[nH]c2=O)S)C(OC1n1cnc2c1ncnc2N)COP(=O)(OC1C(COP(=O)(OC2C(COP(=O)(OC3C(COP(=O)(OC4C(COP(=O)(OC5C(COP(=O)(OC6C(COP(=O)(OC7C(COP(=O)(OC8C(CO)OC(C8OCCOC)n8cc(C)c(=O)[nH]c8=O)S)OC(C7OCCOC)n7cc(C)c(nc7=O)N)S)OC(C6OCCOC)n6cnc7c6ncnc7N)S)OC(C5OCCOC)n5cc(C)c(nc5=O)N)S)OC(C4OCCOC)n4cc(C)c(=O)[nH]c4=O)S)OC(C3OCCOC)n3cc(C)c(=O)[nH]c3=O)S)OC(C2OCCOC)n2cc(C)c(=O)[nH]c2=O)S)OC(C1OCCOC)n1cc(C)c(nc1=O)N)S
Isomeric SMILES COCCO[C@@H]1[C@H](OP(=O)(OC[C@H]2O[C@H]([C@@H]([C@@H]2OP(=O)(OC[C@H]2O[C@H]([C@@H]([C@@H]2OP(=O)(OC[C@H]2O[C@H]([C@@H]([C@@H]2OP(=O)(OC[C@H]2O[C@H]([C@@H]([C@@H]2OP(=O)(OC[C@H]2O[C@H]([C@@H]([C@@H]2OP(=O)(OC[C@H]2O[C@H]([C@@H]([C@@H]2OP(=O)(OC[C@H]2O[C@H]([C@@H]([C@@H]2OP(=O)(OC[C@H]2O[C@H]([C@@H]([C@@H]2OP(=O)(OC[C@H]2O[C@H]([C@@H]([C@@H]2O)OCCOC)n2cnc3c2nc(N)[nH]c3=O)S)OCCOC)n2cnc3c2nc(N)[nH]c3=O)S)OCCOC)n2cc(C)c(=O)[nH]c2=O)S)OCCOC)n2cc(C)c(nc2=O)N)S)OCCOC)n2cnc3c2nc(N)[nH]c3=O)S)OCCOC)n2cc(C)c(=O)[nH]c2=O)S)OCCOC)n2cnc3c2ncnc3N)S)OCCOC)n2cnc3c2ncnc3N)S)OCCOC)n2cc(C)c(=O)[nH]c2=O)S)[C@H](O[C@H]1n1cnc2c1ncnc2N)COP(=O)(O[C@@H]1[C@@H](COP(=O)(O[C@@H]2[C@@H](COP(=O)(O[C@@H]3[C@@H](COP(=O)(O[C@@H]4[C@@H](COP(=O)(O[C@@H]5[C@@H](COP(=O)(O[C@@H]6[C@@H](COP(=O)(O[C@@H]7[C@@H](COP(=O)(O[C@@H]8[C@@H](CO)O[C@H]([C@@H]8OCCOC)n8cc(C)c(=O)[nH]c8=O)S)O[C@H]([C@@H]7OCCOC)n7cc(C)c(nc7=O)N)S)O[C@H]([C@@H]6OCCOC)n6cnc7c6ncnc7N)S)O[C@H]([C@@H]5OCCOC)n5cc(C)c(nc5=O)N)S)O[C@H]([C@@H]4OCCOC)n4cc(C)c(=O)[nH]c4=O)S)O[C@H]([C@@H]3OCCOC)n3cc(C)c(=O)[nH]c3=O)S)O[C@H]([C@@H]2OCCOC)n2cc(C)c(=O)[nH]c2=O)S)O[C@H]([C@@H]1OCCOC)n1cc(C)c(nc1=O)N)S
InChI Key WWFDJIVIDXJAQR-FFWSQMGZSA-N
Classification Click here for help
Compound class Nucleic acid
Compound subclass Antisense oligonucleotide (ASO)
Target survival of motor neuron 2, centromeric (SMN2) with exon 7 skipping mutations
Approved drug? Yes (FDA (2016), EMA (2017))
IUPAC Name Click here for help
O2'-(2-methoxyethyl)-5-methyl-P-thio-uridylyl-(3'->5')-O2'-(2-methoxyethyl)-5-methyl-P-thio-cytidylyl-(3'->5')-O2'-(2-methoxyethyl)-P-thio-adenylyl-(3'->5')-O2'-(2-methoxyethyl)-5-methyl-P-thio-cytidylyl-(3'->5')-O2'-(2-methoxyethyl)-5-methyl-P-thio-uridylyl-(3'->5')-O2'-(2-methoxyethyl)-5-methyl-P-thio-uridylyl-(3'->5')-O2'-(2-methoxyethyl)-5-methyl-P-thio-uridylyl-(3'->5')-O2'-(2-methoxyethyl)-5-methyl-P-thio-cytidylyl-(3'->5')-O2'-(2-methoxyethyl)-P-thio-adenylyl-(3'->5')-O2'-(2-methoxyethyl)-5-methyl-P-thio-uridylyl-(3'->5')-O2'-(2-methoxyethyl)-P-thio-adenylyl-(3'->5')-O2'-(2-methoxyethyl)-P-thio-adenylyl-(3'->5')-O2'-(2-methoxyethyl)-5-methyl-P-thio-uridylyl-(3'->5')-O2'-(2-methoxyethyl)-P-thio-guanylyl-(3'->5')-O2'-(2-methoxyethyl)-5-methyl-P-thio-cytidylyl-(3'->5')-O2'-(2-methoxyethyl)-5-methyl-P-thio-uridylyl-(3'->5')-O2'-(2-methoxyethyl)-P-thio-guanylyl-(3'->5')-O2'-(2-methoxyethyl)-guanosine
International Nonproprietary Names Click here for help
INN number INN
10003 nusinersen
Synonyms Click here for help
ASO-10-27 | BIIB-058 | BIIB058 | Ionis-SMNrx | ISIS 396443 | ISIS SMNRx | ISIS-SMNRx | ISIS396443 | Spinraza®
Database Links Click here for help
CAS Registry No. 1258984-36-9 (source: WHO INN record)
ChEMBL Ligand CHEMBL3301572
DrugBank Ligand DB13161
GtoPdb PubChem SID 328083518
PubChem CID 131801471
Search Google for chemical match using the InChIKey WWFDJIVIDXJAQR-FFWSQMGZSA-N
Search Google for chemicals with the same backbone WWFDJIVIDXJAQR
Search PubMed clinical trials nusinersen
Search PubMed titles nusinersen
Search PubMed titles/abstracts nusinersen
UniChem Compound Search for chemical match using the InChIKey WWFDJIVIDXJAQR-FFWSQMGZSA-N
UniChem Connectivity Search for chemical match using the InChIKey WWFDJIVIDXJAQR-FFWSQMGZSA-N