volanesorsen   Click here for help

GtoPdb Ligand ID: 8681

Synonyms: APOC-III antisense inhibitor | ISIS 304801 | ISIS-APOCIIIRx | Waylivra®
Approved drug
volanesorsen is an approved drug (EMA (2019))
Compound class: Synthetic organic
Comment: Volanesorsen is an antisense oligonucleotide (ASO) designed to reduce levels of apolipoprotein C-III (APOC3) in patients with elevated blood triglyceride levels [2]. Reducing triglycerides via APOC3 could be beneficial in patients with inherited hypertriglyceridemia (e.g. those with familial chylomicronemia syndrome, FCS) [1]. The role of APOC3 in hypertriglyceridemia and the effects APOC3 ASO use are reviewed in [3].
HELM annotation for this RNA (from PubChem) is RNA1{[MOE](A).[sp][MOE](G).[sp][MOE]([5meC]).[sp][MOE](T).[sp][MOE](T).[sp][dR]([5meC]).[sp][dR](T).[sp][dR](T).[sp][dR](G).[sp][dR](T).[sp][dR]([5meC]).[sp][dR]([5meC]).[sp][dR](A).[sp][dR](G).[sp][dR]([5meC]).[sp][MOE](T).[sp][MOE](T).[sp][MOE](T).[sp][MOE](A).[sp][MOE](T)}$$$$.
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 130
Hydrogen bond donors 44
Rotatable bonds 156
Topological polar surface area 3216.79
Molecular weight 7160.03
XLogP 6.58
No. Lipinski's rules broken 4
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 COCCO[C@@H]1[C@H](OP(=S)(OC[C@H]2O[C@H](C[C@@H]2OP(=S)(OC[C@H]2O[C@H](C[C@@H]2OP(=S)(OC[C@H]2O[C@H](C[C@@H]2OP(=S)(OC[C@H]2O[C@H](C[C@@H]2OP(=S)(OC[C@H]2O[C@H](C[C@@H]2OP(=S)(OC[C@H]2O[C@H](C[C@@H]2OP(=S)(OC[C@H]2O[C@H](C[C@@H]2OP(=S)(OC[C@H]2O[C@H](C[C@@H]2OP(=S)(OC[C@H]2O[C@H](C[C@@H]2OP(=S)(OC[C@H]2O[C@H](C[C@@H]2OP(=S)(OC[C@H]2O[C@H]([C@@H]([C@@H]2OP(=S)(OC[C@H]2O[C@H]([C@@H]([C@@H]2OP(=S)(OC[C@H]2O[C@H]([C@@H]([C@@H]2OP(=S)(OC[C@H]2O[C@H]([C@@H]([C@@H]2OP(=S)(OC[C@H]2O[C@H]([C@@H]([C@@H]2O)OCCOC)n2cc(C)c(=O)[nH]c2=O)O)OCCOC)n2cnc3c2ncnc3N)O)OCCOC)n2cc(C)c(=O)[nH]c2=O)O)OCCOC)n2cc(C)c(=O)[nH]c2=O)O)OCCOC)n2cc(C)c(=O)[nH]c2=O)O)n2cc(C)c(nc2=O)N)O)n2cnc3c2nc(N)[nH]c3=O)O)n2cnc3c2ncnc3N)O)n2cc(C)c(nc2=O)N)O)n2cc(C)c(nc2=O)N)O)n2cc(C)c(=O)[nH]c2=O)O)n2cnc3c2nc(N)[nH]c3=O)O)n2cc(C)c(=O)[nH]c2=O)O)n2cc(C)c(=O)[nH]c2=O)O)n2cc(C)c(nc2=O)N)O)[C@H](O[C@H]1n1cc(C)c(=O)[nH]c1=O)COP(=S)(O[C@@H]1[C@@H](COP(=S)(O[C@@H]2[C@@H](COP(=S)(O[C@@H]3[C@@H](COP(=S)(O[C@@H]4[C@@H](CO)O[C@H]([C@@H]4OCCOC)n4cnc5c4ncnc5N)O)O[C@H]([C@@H]3OCCOC)n3cnc4c3nc(N)[nH]c4=O)O)O[C@H]([C@@H]2OCCOC)n2cc(C)c(nc2=O)N)O)O[C@H]([C@@H]1OCCOC)n1cc(C)c(=O)[nH]c1=O)O
Isomeric SMILES COCCO[C@@H]1[C@H](OP(=S)(OC[C@H]2O[C@H](C[C@@H]2OP(=S)(OC[C@H]2O[C@H](C[C@@H]2OP(=S)(OC[C@H]2O[C@H](C[C@@H]2OP(=S)(OC[C@H]2O[C@H](C[C@@H]2OP(=S)(OC[C@H]2O[C@H](C[C@@H]2OP(=S)(OC[C@H]2O[C@H](C[C@@H]2OP(=S)(OC[C@H]2O[C@H](C[C@@H]2OP(=S)(OC[C@H]2O[C@H](C[C@@H]2OP(=S)(OC[C@H]2O[C@H](C[C@@H]2OP(=S)(OC[C@H]2O[C@H](C[C@@H]2OP(=S)(OC[C@H]2O[C@H]([C@@H]([C@@H]2OP(=S)(OC[C@H]2O[C@H]([C@@H]([C@@H]2OP(=S)(OC[C@H]2O[C@H]([C@@H]([C@@H]2OP(=S)(OC[C@H]2O[C@H]([C@@H]([C@@H]2OP(=S)(OC[C@H]2O[C@H]([C@@H]([C@@H]2O)OCCOC)n2cc(C)c(=O)[nH]c2=O)O)OCCOC)n2cnc3c2ncnc3N)O)OCCOC)n2cc(C)c(=O)[nH]c2=O)O)OCCOC)n2cc(C)c(=O)[nH]c2=O)O)OCCOC)n2cc(C)c(=O)[nH]c2=O)O)n2cc(C)c(nc2=O)N)O)n2cnc3c2nc(N)[nH]c3=O)O)n2cnc3c2ncnc3N)O)n2cc(C)c(nc2=O)N)O)n2cc(C)c(nc2=O)N)O)n2cc(C)c(=O)[nH]c2=O)O)n2cnc3c2nc(N)[nH]c3=O)O)n2cc(C)c(=O)[nH]c2=O)O)n2cc(C)c(=O)[nH]c2=O)O)n2cc(C)c(nc2=O)N)O)[C@H](O[C@H]1n1cc(C)c(=O)[nH]c1=O)COP(=S)(O[C@@H]1[C@@H](COP(=S)(O[C@@H]2[C@@H](COP(=S)(O[C@@H]3[C@@H](COP(=S)(O[C@@H]4[C@@H](CO)O[C@H]([C@@H]4OCCOC)n4cnc5c4ncnc5N)O)O[C@H]([C@@H]3OCCOC)n3cnc4c3nc(N)[nH]c4=O)O)O[C@H]([C@@H]2OCCOC)n2cc(C)c(nc2=O)N)O)O[C@H]([C@@H]1OCCOC)n1cc(C)c(=O)[nH]c1=O)O
InChI Key IJUQCWMZCMFFJP-GQSLRNSLSA-N
References
1. Gaudet D, Brisson D, Tremblay K, Alexander VJ, Singleton W, Hughes SG, Geary RS, Baker BF, Graham MJ, Crooke RM et al.. (2014)
Targeting APOC3 in the familial chylomicronemia syndrome.
N Engl J Med, 371 (23): 2200-6. [PMID:25470695]
2. Graham MJ, Lee RG, Bell 3rd TA, Fu W, Mullick AE, Alexander VJ, Singleton W, Viney N, Geary R, Su J et al.. (2013)
Antisense oligonucleotide inhibition of apolipoprotein C-III reduces plasma triglycerides in rodents, nonhuman primates, and humans.
Circ Res, 112 (11): 1479-90. [PMID:23542898]
3. Lee RG, Crosby J, Baker BF, Graham MJ, Crooke RM. (2013)
Antisense technology: an emerging platform for cardiovascular disease therapeutics.
J Cardiovasc Transl Res, 6 (6): 969-80. [PMID:23856914]
4. Paik J, Duggan S. (2019)
Volanesorsen: First Global Approval.
Drugs, 79 (12): 1349-1354. [PMID:31301033]