DT-Web

DB05528 - Mipomersen


Identification
Name Mipomersen
Accession Number DB05528
Type small molecule
Description Mipomersen sodium, which was known as the investigational drug, isis-301012, is the salt form of a synthetic phosphorothioate oligonucleotide. Mipomersen sodium prevents the formation of apo B-100, resulting in a decrease in the levels of apolipoprotein B (apo B), low density lipoprotein (LDL), and total cholesterol. Mipomersen is indicated in patients with homozygous familial hypercholesterolemia as an adjunct to diet and other lipid-lowering medications. It is marketed under the brand name Kynamro in the United States, and the FDA label includes a black box warning of hepatoxicity. Specifically, elevations in the liver enzymes, i.e. transaminases, and in liver fat (hepatic steatosis) have been reported. Due to this serious risk of liver toxicity, mipomersen sodium is only available to patients under the restricted program called Kynamro(TM) Risk Evaluation and Mitigation Strategy program.
Structure
MOL SDF PDB SMILES InChI
Categories (*)
Molecular Weight Not Available
Groups approved
Monoisotopic Weight Not Available
Pharmacology
Indication Used in patients with homozygous familial hypercholesterolemia as an adjunct to diet and other lipid-lowering medications.
Mechanism of action Mipomersen binds to the mRNA that codes for apoB-100. This binding leads to double-stranded RNA, which is degraded by RNase H and prevents translation of the mRNA to form the apo B-100 protein.
Absorption The maximum mipomersen concentration is reached in about 3-4 hours after subcutaneous injection. Additionally the bioavailability of mipomersn is dose-dependant and ranges from 54%-78%.
Protein binding Plasma protein binding for mipomersen is greater than or equal to 90%.
Biotransformation Mipomersem is metabolized by endonucleases. Once degraded into shorter oligonucleotides, it is metabolized further by exonucleases.
Route of elimination 24 hours after mipomersem administration, less than 4% of mipomersem and/or it's metabolites were excreted in the urine.
Toxicity The FDA label includes a black box warning of mipomersem induced hepatoxicity. Other less serious adverse effects include nausea, headache, fatigue, local injection site reactions, and flu-like symptoms.
Affected organisms
  • Humans and other mammals
Interactions
Drug Interactions
Drug Mechanism of interaction
Ethanol The combination of these drugs will likely enhance mipomersen related hepatotoxicity. Therefore patients using both these drugs, should limit their alcohol to a daily maximum of 1 drink (or equivalent).
Food Interactions
  • Limit alcohol to a daily maximum of 1 drink (or equivalent) while using mipomersen sodium.

Targets


ApoB-100 mRNA
Name ApoB-100 mRNA
Gene Name Not Available
Pharmacological action yes
Actions binder
References
  • Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. - Pubmed
  • FDA label. -
DTHybrid score Not Available

Predictions


Id Partner name Gene Name Score
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