| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| Other Sizes |
| Targets |
Muvalaplin tetrahydrochloride targets lipoprotein(a) (Lp(a)), a low-density lipoprotein (LDL)-like particle containing apolipoprotein(a) (apo(a)) covalently linked to apolipoprotein B-100. Elevated Lp(a) is a genetically determined, independent risk factor for atherosclerotic cardiovascular disease, aortic stenosis, and thrombosis. Muvalaplin is designed to block the assembly of Lp(a) by inhibiting the interaction between apo(a) and apoB-100, thereby reducing circulating Lp(a) levels.
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| ln Vitro |
Specific in vitro activity data for Muvalaplin tetrahydrochloride is not provided. As an inhibitor of Lp(a) assembly, it would be evaluated in cell-based or cell-free assays measuring the interaction between apo(a) and apoB-100. The compound is reported to be orally active and is being developed for cardiovascular indications. The tetrahydrochloride salt enhances water solubility and oral absorption.
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| ln Vivo |
Muvalaplin tetrahydrochloride is an orally active Lp(a) inhibitor. While specific in vivo data is not provided, the compound is in development for the treatment of elevated Lp(a) levels. In animal models, it would be expected to reduce circulating Lp(a) levels in a dose-dependent manner. The development of this compound represents a novel therapeutic approach to reducing cardiovascular risk in patients with elevated Lp(a).
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| Enzyme Assay |
Not applicable. Muvalaplin tetrahydrochloride is a drug in development, and its activity is measured in cell-based assays or in vivo models. For binding studies, a surface plasmon resonance (SPR) or fluorescence polarization (FP) assay could be used to measure the binding of Muvalaplin to apo(a) or apoB-100. However, specific protocols are not provided in the search results.
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| Cell Assay |
The cellular activity of Muvalaplin tetrahydrochloride can be assessed in HepG2 cells, which express both apo(a) and apoB-100. Procedure: HepG2 cells are seeded in 6-well plates (2×10⁵ cells/well) and treated with varying concentrations of Muvalaplin tetrahydrochloride (0.1-1000 nM) for 24-48 hours. Cell culture supernatants are collected, and Lp(a) levels are quantified by a specific Lp(a) ELISA. Cell viability is assessed by MTT assay. A reduction in Lp(a) levels in the culture supernatant indicates inhibition of Lp(a) assembly. IC50 values are calculated from dose-response curves.
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| Animal Protocol |
The in vivo efficacy can be evaluated in a transgenic mouse model expressing human apo(a) and apoB-100. Procedure: Female transgenic mice expressing both human apo(a) and apoB-100 (6-8 weeks, n=10 per group) are administered Muvalaplin tetrahydrochloride orally at doses of 10, 30, and 100 mg/kg once daily for 4 weeks. Control groups receive vehicle only. Blood samples are collected at baseline and weekly for serum Lp(a) measurement by ELISA. At study endpoint, mice are euthanized, and plasma lipid profiles (total cholesterol, LDL-C, HDL-C, triglycerides) are measured. A reduction in serum Lp(a) levels compared to baseline and vehicle control indicates efficacy.
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| ADME/Pharmacokinetics |
Muvalaplin tetrahydrochloride is orally active, indicating good oral bioavailability. As a small molecule with a molecular weight of 856.75 g/mol, it is relatively large, but the tetrahydrochloride salt may enhance solubility and absorption. Specific PK parameters (t½, Cmax, AUC) are not provided. The compound is in development, and further PK studies are ongoing.
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| Toxicity/Toxicokinetics |
Specific toxicology data for Muvalaplin tetrahydrochloride is not provided. As a novel inhibitor of Lp(a) assembly, its safety profile is under investigation. Potential off-target effects may include modulation of other lipoprotein pathways or hepatotoxicity. Since the compound is in clinical development, full safety data from preclinical and clinical studies would be required to establish its safety profile.
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| References | |
| Additional Infomation |
Muvalaplin tetrahydrochloride (LY3473329) is an orally active small molecule inhibitor of lipoprotein(a) (Lp(a)) assembly, currently in clinical development. Elevated Lp(a) is a major, genetically determined, independent risk factor for cardiovascular disease, affecting approximately 20% of the population. There are no approved pharmacotherapies specifically targeting Lp(a). Muvalaplin represents a novel approach to reducing this residual cardiovascular risk by inhibiting the interaction between apolipoprotein(a) and apoB-100, thereby preventing Lp(a) formation. This product is for research use only and is not an approved drug.
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| Molecular Formula |
C42H58CL4N4O6
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|---|---|
| Molecular Weight |
856.75
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| CAS # |
2565656-71-3
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| Related CAS # |
Muvalaplin; 2565656-70-2
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| Appearance |
White to off-white solid powder
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| SMILES |
OC([C@H]([C@H]1CCNC1)CC2=CC(CN(CC3=CC(C[C@@H]([C@H]4CCNC4)C(O)=O)=CC=C3)CC5=CC(C[C@@H]([C@H]6CCNC6)C(O)=O)=CC=C5)=CC=C2)=O.[H]Cl.[H]Cl.[H]Cl.[H]Cl
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| Synonyms |
LY3473329 tetrahydrochloride
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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: (1). Please store this product in a sealed and protected environment, 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 : ~133.33 mg/mL (~155.62 mM; with ultrasonication (<60°C))
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1672 mL | 5.8360 mL | 11.6720 mL | |
| 5 mM | 0.2334 mL | 1.1672 mL | 2.3344 mL | |
| 10 mM | 0.1167 mL | 0.5836 mL | 1.1672 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
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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