Mivelsiran
Based on 1 Customer Validation
Mivelsiran (ALN-APP) is an siRNA targeting the β-amyloid precursor protein (APP). Mivelsiran induces sequence-specific degradation of APP mRNA via RNA interference, thereby reducing the levels of APP protein and downstream amyloid cleavage products. Mivelsiran reduces β-amyloid protein levels in the brain, alleviates neuroinflammation, and attenuates microglial proliferation. Mivelsiran can be used for research on early-onset Alzheimer's disease.
Para uso exclusivo en investigación. No vendemos a pacientes.
- Pureza: 95.96%
- No. CAS: 2572991-83-2
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Almacenamiento:
-20°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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Actividad biológica
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Chemical Information
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Help & FAQs
Actividad biológica
Descripciòn
In Vitro
Mivelsiran does not induce cytokine release or immune activation in ex vivo human whole blood[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Mivelsiran (60-120 µg; i.c.v.; single dose) suppresses APP expression, reduces neuroinflammation, and normalizes hyperactive behavior in cerebrovascular amyloid Nos2−/− (CVN) Alzheimer's disease mice[1].
Mivelsiran (300 µg; i.c.v.; two doses at 3 and 6 months, single dose at 8 months) reduces amyloid beta levels, neuroinflammatory markers, and abnormal anxiety-like behavior in 5xFAD Alzheimer's disease mice when administered early, while late intervention does not improve behavioral deficits despite reducing pathological markers[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Sprague Dawley (male)[1]
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Dosage:0.07 mg; 0.3 mg; 0.9 mg
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Administration:i.t.; single dose; monthly for 5 consecutive months
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Result:Reduced SOD1 mRNA to below 50% in the thoracic spinal cord, cerebellum, and frontal cortex at day 28 for all single doses.
Reduced SOD1 mRNA to 25% of control levels across thoracic spinal cord, cerebellum, and frontal cortex with the 0.9 mg dose.
Maintained silencing exceeding 50% for over three months in most CNS regions (spinal cord segments, cerebellum, frontal cortex, temporal cortex, hippocampus) with the 0.9 mg dose.
Maintained silencing above 50% for five months in the spinal cord and frontal cortex with the 0.9 mg dose.
Produced positive silencing effects over five months with the 0.3 mg monthly dosing regimen.
Showed cranial distribution via cerebrospinal fluid, reaching the cortex, hippocampus, olfactory bulb, and brainstem, with uptake observed in neurons, astrocytes, and microglia.
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Animal Model:Cynomolgus Monkey[1]
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Dosage:45 mg; 60 mg
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Administration:i.t.; single dose
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Result:Achieved 70-80% knockdown of target mRNA across multiple CNS regions with the 60 mg dose.
Reached maximal silencing within one week, sustained above 75% for ~2.5 months, declined to 50% by 4.5 months, and returned near baseline by 9 months with the 60 mg dose.
Reduced cerebrospinal fluid levels of soluble APPα (sAPPα) and soluble APPβ (sAPPβ) to below 25% for up to two months, and below 50% for five months with both doses.
Showed no treatment-related microscopic neuropathology in the brain, spinal cord, or dorsal root ganglia.
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Animal Model:Homozygous Tg-hAPPSwDl/mNos2−/− (CVN) (6-12 months old)[1]
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Dosage:60 µg; 120 µg
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Administration:i.c.v.; single dose
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Result:Reduced APP expression (mRNA and peptide levels) at 30 days post-administration with the 60 µg dose.
Suppressed APP mRNA in the ventral cortex for 60 days with the 120 µg dose, with effects observed in other brain regions over extended time points.
Showed a non-statistically significant reduction in Aβ40 immunostaining in the cortex and hippocampus.
Showed a statistically significant reduction in Iba1 immunostaining (microgliosis) in the cortex and hippocampus compared to untreated controls.
Exhibited reduced distance traveled and rearing frequency in the open field test, indicating mitigated hyperactivity.
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Animal Model:5xFAD (transgenic, expressing five familial Alzheimer's disease mutations)[1]
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Dosage:300 µg
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Administration:i.c.v.; two doses at 3 and 6 months; single dose at 8 months
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Result:Significantly decreased cortical Aβ40 and Aβ42 levels with early intervention (two doses at 3 and 6 months).
Reduced plasma neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) levels with early intervention (two doses at 3 and 6 months).
Produced a dose-dependent decrease in time spent in the open arms of the elevated plus maze, with the robust early intervention group exhibiting behavior comparable to healthy controls at 8 and 12 months.
Reduced Aβ40, Aβ42, NfL, and GFAP levels with late intervention (single dose at 8 months).
Did not normalize elevated plus maze behavior with late intervention (single dose at 8 months).
Ensayo clínico
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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No. CAS 2572991-83-2
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Appearance Solid
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Color White to off-white
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SMILES
[Mivelsiran]
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Synonyms
ALN-APP
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
-20°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Pureza y Documentación
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Ficha de datos (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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Instrucciones de manejo (2242 KB)
Referencias
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Mivelsiran Related Classifications
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