Muvalaplin tetrahydrochloride
Based on 1 Customer Validation
Muvalaplin tetrahydrochloride (LY3473329 tetrahydrochloride) is an orally active small molecule apolipoprotein a (apolipoprotein a) inhibitor that binds to the KIV8 domain (Kd = 22 nM) and kringle IV domains 7 and 8, blocks the non-covalent interaction between apo (a) and apoB-100, and prevents Lp (a) assembly, thereby lowering circulating Lp (a) levels. Muvalaplin tetrahydrochloride can be used in research on atherosclerotic cardiovascular disease.
Nos produits utilisent uniquement pour la recherche. Nous ne vendons pas aux patients.
- Pureté : 99.55%
- CAS No.: 2565656-71-3
- Formule: C42H58Cl4N4O6
- Masse moléculaire:856.75
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Stockage:
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Activité biologique
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Chemical Information
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Solvant et solubilité
- Protocole
- Pureté et documentation
- Références
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Help & FAQs
Activité biologique
Description
IC50 & Target
[3]|
apo(a) |
apoB |
In Vitro
Muvalaplin tetrahydrochloride (LY3473329 tetrahydrochloride) (2 h) effectively inhibits the formation of Lp (a) particles with an IC50 of 0.09 nM[3].
Muvalaplin tetrahydrochloride does not affect plasmin activity and reduces Lp (a) formation in a cell-free in vitro assembly assay[1].
Muvalaplin tetrahydrochloride selectively binds to the apo (a) KIV8 domain with a Kd of 22 nM, demonstrating selectivity over the KIV2 domain[3].
Muvalaplin tetrahydrochloride (0.001-1000 µM; 15 h) does not directly modulate plasminogen activation or plasmin activity in human platelet-poor plasma[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
Parmacokinetics
| Species | Dose | Route | Plasma Concentration | AUC0-96 | Cmax | Tmax |
|---|---|---|---|---|---|---|
| Mice[3] | 1 mg/kg | p.o. | 28.4 nM | / | / | / |
| Mice[3] | 3 mg/kg | p.o. | 97.3 nM | / | / | / |
| Mice[3] | 10 mg/kg | p.o. | 215 nM | / | / | / |
| Mice[3] | 30 mg/kg | p.o. | 264 nM | / | / | / |
| Monkey[3] | 1 mg/kg | p.o. | / | 35,800 nM·h | 911 nM | 7 h |
| Monkey[3] | 10 mg/kg | p.o. | / | 207,000 nM·h | 3,470 nM | 0.5 h |
| Monkey[3] | 100 mg/kg | p.o. | / | 294,000 nM·h | 4,850 nM | 1 h |
In Vivo
Muvalaplin tetrahydrochloride (1-100 mg/kg; p.o.; twice daily; 5 days) reduces Lp (a) levels in Lp (a) transgenic mice with an ED50 of 3 mg/kg and a maximum reduction of 92%[3].
Muvalaplin tetrahydrochloride (1-100 mg/kg; p.o.; q.d.; 14 days) reduces median Lp (a) levels by up to 71% in cynomolgus monkeys[3].
Muvalaplin tetrahydrochloride (3.2-31.6 mg/kg; p.o.; QD; 4 days) reduces plasma plasmin activity and plasminogen protein levels in rats in a dose-dependent manner[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Lp(a) double transgenic mice (B6.SJL-Tg(APOB)1102Sgy Tg(Alb-LPA)32Arte; female; 7-17 months)[3]
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Dosage:1, 3, 10, 30, and 100 mg/kg
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Administration:p.o.; BID; 5 days
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Result:Reduced Lp(a) levels with an absolute ED50 of 3 mg/kg.
Achieved a maximum Lp(a) reduction of 92% after five days of BID oral dosing.
Increased plasma levels of LY3473329-HCl salt in a dose-dependent manner.
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Animal Model:Macaca fascicularis (female or male; 2.0-5.0 kg)[3]
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Dosage:1, 10, and 100 mg/kg
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Administration:p.o.; QD; 14 days
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Result:Reduced median Lp(a) levels in a dose-dependent manner by up to 71% in the 100 mg/kg once daily (QD) cohort, compared with baseline.
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Animal Model:Sprague Dawley (male; 8-9 weeks old; average body weight 310 g)[3]
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Dosage:3.2, 10.5, and 31.6 mg/kg
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Administration:p.o.; QD; 4 days
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Result:Decreased plasma plasmin activity.
Decreased plasma levels of plasminogen protein in a dose-dependent manner.
Chemical Information
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CAS No. 2565656-71-3
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Appearance Solid
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Masse moléculaire 856.75
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Formule C42H58Cl4N4O6
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Color White to off-white
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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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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Solvant et solubilité
In Vitro:
H2O : ≥ 100 mg/mL (116.72 mM)
* "≥" means soluble, but saturation unknown.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Protocole
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Research Protocol for Cardiovascular Diseases
Cardiovascular disease can be modeled as maladaptive cardiac remodeling, where ischemic injury or pressure overload activates inflammatory signaling, fibroblast activation, extracellular-matrix deposition, cardiomyocyte hypertrophy, vascular remodeling, and progressive ventricular dysfunction. The TGF-β/SMAD axis is a central profibrotic pathway after myocardial injury and pressure overload, while innate immune and cytokine pathways regulate leukocyte recruitment, scar formation, and adverse remodeling. Key unresolved questions include which inflammatory signals are reparative versus harmful, when fibrosis is protective versus maladaptive, and whether pathway inhibition improves function without weakening necessary infarct healing or compensatory remodeling.
Pureté et documentation
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Fiche technique (282 KB)
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SDS (252 KB)
- English - EN (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Instruction de manipulation (2659 KB)
Références
[2]. Nicholls SJ, et al. Muvalaplin, an Oral Small Molecule Inhibitor of Lipoprotein(a) Formation: A Randomized Clinical Trial. JAMA. 2023 Sep 19;330(11):1042-1053. [Content Brief]
[3]. Diaz N, et al. Discovery of potent small-molecule inhibitors of lipoprotein(a) formation. Nature. 2024 May;629(8013):945-950. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| H2O | 1 mM | 1.1672 mL | 5.8360 mL | 11.6720 mL | 29.1800 mL |
| 5 mM | 0.2334 mL | 1.1672 mL | 2.3344 mL | 5.8360 mL | |
| 10 mM | 0.1167 mL | 0.5836 mL | 1.1672 mL | 2.9180 mL | |
| 15 mM | 0.0778 mL | 0.3891 mL | 0.7781 mL | 1.9453 mL | |
| 20 mM | 0.0584 mL | 0.2918 mL | 0.5836 mL | 1.4590 mL | |
| 25 mM | 0.0467 mL | 0.2334 mL | 0.4669 mL | 1.1672 mL | |
| 30 mM | 0.0389 mL | 0.1945 mL | 0.3891 mL | 0.9727 mL | |
| 40 mM | 0.0292 mL | 0.1459 mL | 0.2918 mL | 0.7295 mL | |
| 50 mM | 0.0233 mL | 0.1167 mL | 0.2334 mL | 0.5836 mL | |
| 60 mM | 0.0195 mL | 0.0973 mL | 0.1945 mL | 0.4863 mL | |
| 80 mM | 0.0146 mL | 0.0730 mL | 0.1459 mL | 0.3648 mL | |
| 100 mM | 0.0117 mL | 0.0584 mL | 0.1167 mL | 0.2918 mL |
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Muvalaplin tetrahydrochloride Related Classifications
HY-46749 Related Classifications
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