mipomersen   Click here for help

GtoPdb Ligand ID: 7364

Synonyms: ISIS 301012 parent acid | isis-301012 | Kynamro®
Approved drug
mipomersen is an approved drug (FDA (2013))
Compound class: Nucleic acid
Comment: Mipomersen is a synthetic phosphorothioate antisense oligonucleotide (ASO) that is designed to block hepatic production of apolipoprotein B-100 as a mechanism to reduce levels of very low-density lipoprotein (vLDL) and LDL. It is a second generation 2′-O-methoxyethyl containing ASO that is formulated as a sodium adduct for clinical administration.
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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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.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES COCCOC1C(SP(=O)(OCC2OC(CC2SP(=O)(OCC2OC(CC2SP(=O)(OCC2OC(CC2SP(=O)(OCC2OC(CC2SP(=O)(OCC2OC(CC2SP(=O)(OCC2OC(CC2SP(=O)(OCC2OC(CC2SP(=O)(OCC2OC(CC2SP(=O)(OCC2OC(CC2SP(=O)(OCC2OC(CC2SP(=O)(OCC2OC(C(C2SP(=O)(OCC2OC(C(C2SP(=O)(OCC2OC(C(C2SP(=O)(OCC2OC(C(C2SP(=O)(OCC2OC(C(C2O)OCCOC)n2cc(C)c(nc2=O)N)[O-])OCCOC)n2cc(C)c(nc2=O)N)[O-])OCCOC)n2cnc3c2ncnc3N)[O-])OCCOC)n2cc(C)c(nc2=O)N)[O-])OCCOC)n2cnc3c2nc(N)[nH]c3=O)[O-])n2cc(C)c(nc2=O)N)[O-])n2cc(C)c(=O)[nH]c2=O)[O-])n2cc(C)c(=O)[nH]c2=O)[O-])n2cc(C)c(nc2=O)N)[O-])n2cnc3c2nc(N)[nH]c3=O)[O-])n2cc(C)c(=O)[nH]c2=O)[O-])n2cc(C)c(nc2=O)N)[O-])n2cc(C)c(=O)[nH]c2=O)[O-])n2cnc3c2nc(N)[nH]c3=O)[O-])n2cnc3c2ncnc3N)[O-])C(OC1n1cc(C)c(nc1=O)N)COP(=O)(SC1C(COP(=O)(SC2C(COP(=O)(SC3C(COP(=O)(SC4C(CO)OC(C4OCCOC)n4cnc5c4nc(N)[nH]c5=O)[O-])OC(C3OCCOC)n3cc(C)c(nc3=O)N)[O-])OC(C2OCCOC)n2cc(C)c(nc2=O)N)[O-])OC(C1OCCOC)n1cc(C)c(=O)[nH]c1=O)[O-]
Isomeric SMILES COCCO[C@@H]1[C@H](SP(=O)(OC[C@H]2O[C@H](C[C@@H]2SP(=O)(OC[C@H]2O[C@H](C[C@@H]2SP(=O)(OC[C@H]2O[C@H](C[C@@H]2SP(=O)(OC[C@H]2O[C@H](C[C@@H]2SP(=O)(OC[C@H]2O[C@H](C[C@@H]2SP(=O)(OC[C@H]2O[C@H](C[C@@H]2SP(=O)(OC[C@H]2O[C@H](C[C@@H]2SP(=O)(OC[C@H]2O[C@H](C[C@@H]2SP(=O)(OC[C@H]2O[C@H](C[C@@H]2SP(=O)(OC[C@H]2O[C@H](C[C@@H]2SP(=O)(OC[C@H]2O[C@H]([C@@H]([C@@H]2SP(=O)(OC[C@@H]2O[C@@H]([C@H]([C@H]2SP(=O)(OC[C@@H]2O[C@@H]([C@H]([C@H]2SP(=O)(OC[C@@H]2O[C@@H]([C@H]([C@H]2SP(=O)(OC[C@@H]2O[C@@H]([C@H]([C@H]2O)OCCOC)n2cc(C)c(nc2=O)N)[O-])OCCOC)n2cc(C)c(nc2=O)N)[O-])OCCOC)n2cnc3c2ncnc3N)[O-])OCCOC)n2cc(C)c(nc2=O)N)[O-])OCCOC)n2cnc3c2nc(N)[nH]c3=O)[O-])n2cc(C)c(nc2=O)N)[O-])n2cc(C)c(=O)[nH]c2=O)[O-])n2cc(C)c(=O)[nH]c2=O)[O-])n2cc(C)c(nc2=O)N)[O-])n2cnc3c2nc(N)[nH]c3=O)[O-])n2cc(C)c(=O)[nH]c2=O)[O-])n2cc(C)c(nc2=O)N)[O-])n2cc(C)c(=O)[nH]c2=O)[O-])n2cnc3c2nc(N)[nH]c3=O)[O-])n2cnc3c2ncnc3N)[O-])[C@H](O[C@H]1n1cc(C)c(nc1=O)N)COP(=O)(S[C@@H]1[C@@H](COP(=O)(S[C@@H]2[C@@H](COP(=O)(S[C@@H]3[C@@H](COP(=O)(S[C@@H]4[C@@H](CO)O[C@H]([C@@H]4OCCOC)n4cnc5c4nc(N)[nH]c5=O)[O-])O[C@H]([C@@H]3OCCOC)n3cc(C)c(nc3=O)N)[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 TZRFSLHOCZEXCC-HIVFKXHNSA-A

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
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Summary of Clinical Use Click here for help
Used as an adjunct to diet and other lipid-lowing medications in the treatment of homozygous familial hypercholesterolemia. Kynamro was the first systemically administered ASO to be approved by the FDA.
Mechanism Of Action and Pharmacodynamic Effects Click here for help
Mipomersen is a cholesterol-reducing antisense therapeutic. It targets the messenger RNA for apolipoprotein B. Mipomersen binds to the mRNA of one of apolipoprotein B's isoforms, Apo B-100 (Uniprot P04114). The resulting double-stranded RNA is degraded by RNase H, preventing translation of the mRNA and formation of the apo B-100 protein. Mipomersen binds at nucleotide positions 3249-3268 relative to the published sequence provided in GenBank accession number NM_000384.
External links Click here for help
For extended ADME data see the following:

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