| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
The compound targets apolipoprotein B-100 (apoB-100) mRNA. Apolipoprotein B-100 is the major structural protein of LDL and VLDL particles and is essential for the assembly and secretion of these atherogenic lipoproteins. Mipomersen is a 20-base phosphorothioate ASO complementary to the apoB-100 mRNA. Upon binding, the duplex is recognized and cleaved by RNase H, leading to reduced apoB-100 mRNA levels, decreased apoB-100 protein synthesis, and consequently lower plasma LDL-cholesterol levels. Mipomersen primarily distributes to the liver, where apoB-100 is synthesized.
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| ln Vitro |
Apolipoprotein (apo) B is a large amphipathic protein that plays an important role in the functioning of human lipoproteins. Mipomersen is primarily distributed in the liver and reduces the production of apoB-100, the main structural protein of atherogenic lipoproteins, including low-density lipoprotein (LDL). This lowers heart disease LDL-cholesterol and apoB-100 concentrations. Additionally, ApoB-100 binds to the LDL receptor and facilitates the endocytosis of LDL [2].
In vitro, mipomersen demonstrates potent and sequence-specific reduction of apoB-100 mRNA and protein levels in hepatocytes. The compound also has anti-HCV effects, reducing the infectivity of hepatitis C virus (HCV), likely through off-target effects on viral RNA or host factors involved in viral replication. However, its primary mechanism and clinical utility are for lowering LDL cholesterol in patients with HoFH. |
| ln Vivo |
The in vivo efficacy of mipomersen was demonstrated in clinical trials. In patients with HoFH, subcutaneous administration of mipomersen (200 mg once weekly) resulted in significant reductions in LDL-cholesterol levels (approximately 25-30% reduction from baseline) compared to placebo. The drug is well tolerated with long-term use, though side effects such as injection site reactions and liver enzyme elevations are observed. Mipomersen is approved as an adjunct to lipid-lowering therapies for HoFH.
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| Enzyme Assay |
Mipomersen is an antisense oligonucleotide, not a classical enzyme inhibitor, so biochemical enzyme assays are not applicable. The target engagement is measured by quantifying apoB-100 mRNA levels in cells or liver tissue using qRT-PCR. The mechanism of action is confirmed by measuring apoB-100 protein levels in cell lysates or culture supernatants by ELISA or Western blot.
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| Cell Assay |
The cellular activity of mipomersen is assessed in primary human hepatocytes or HepG2 human hepatoma cells. Cells are seeded in 6-well plates and treated with varying concentrations of mipomersen (1-1000 nM) complexed with a transfection reagent (e.g., Lipofectamine 2000) for 24-48 hours, as ASOs are generally taken up by cells via endocytosis without the need for transfection, but efficiency may vary. After treatment, cells are harvested, and total RNA is extracted. ApoB-100 mRNA levels are measured by qRT-PCR using specific primers. Culture supernatants may be collected to measure apoB-100 protein secretion by ELISA. For HCV studies, Huh-7 cells or primary human hepatocytes are infected with HCV, and mipomersen is added to evaluate its effect on viral replication by measuring HCV RNA levels by qRT-PCR.
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| Animal Protocol |
In vivo animal studies were performed during drug development, typically using a high-cholesterol diet-fed mouse model or a human apoB transgenic mouse model. Female C57BL/6 mice are fed a high-fat/high-cholesterol diet for 4-6 weeks to induce hypercholesterolemia. Mipomersen is administered via subcutaneous injection at doses of 25-100 mg/kg once weekly for 4 weeks. Plasma lipid levels (total cholesterol, LDL cholesterol, triglycerides) are measured at baseline and weekly. Liver tissues are harvested at the end of the study for analysis of apoB-100 mRNA levels by qRT-PCR and histopathological assessment of hepatic steatosis.
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| ADME/Pharmacokinetics |
Mipomersen is administered by subcutaneous injection. In clinical studies, the elimination half-life is approximately 1-2 months, which supports once-weekly dosing. The drug is primarily distributed to the liver (accounting for ~70% of the dose) and to a lesser extent to the kidneys and other organs. Mipomersen is not orally bioavailable; it is degraded by nucleases in the gastrointestinal tract. The drug is cleared primarily by nucleases in the liver and kidney, and to a lesser extent by renal excretion.
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| Toxicity/Toxicokinetics |
Mipomersen has several known toxicities. The most common adverse events are injection site reactions (erythema, pain, swelling) occurring in approximately 75% of patients. More serious side effects include elevations in liver transaminases (ALT and AST), hepatic steatosis (fatty liver), and increased liver fat content, which can be detected by MRI. These liver effects are related to the accumulation of lipids in the liver as a result of reduced secretion of VLDL. Hepatotoxicity is dose-dependent and generally reversible upon discontinuation of therapy. Mipomersen carries a boxed warning for hepatotoxicity and is available only through a restricted distribution program.
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| References | |
| Additional Infomation |
Mipomersen (brand name: Kynamro) was approved by the U.S. FDA in 2013 for the treatment of homozygous familial hypercholesterolemia (HoFH), a rare genetic disorder characterized by extremely high LDL-cholesterol levels and premature cardiovascular disease. It is used as an adjunct to other lipid-lowering therapies (e.g., statins, ezetimibe, LDL apheresis) in patients with HoFH. Mipomersen is not approved for other types of hypercholesterolemia due to the risk of hepatotoxicity. As of the latest updates, it is available by prescription under a restricted distribution program and can be obtained as a research-grade chemical.
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| CAS # |
629167-92-6
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| Related CAS # |
Mipomersen;1000120-98-8
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| Appearance |
White to off-white solid powder
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
H2O : ~100 mg/mL (~13.17 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (13.17 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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