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.
商品は「研究用試薬」です。人や動物の医療用・臨床診断用・食品用の製品ではありません。
研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- 純度: 95.96%
- CAS 番号: 2572991-83-2
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保管条件:
-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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生物活性
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化学情報
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
生物活性
製品説明
体外実験
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.
体内実験
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).
臨床実験
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
化学情報
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CAS 番号 2572991-83-2
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性状 Solid
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Color White to off-white
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SMILES
[Mivelsiran]
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別名
ALN-APP
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
-20°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
純度とドキュメンテーション
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データシート (282 KB)
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SDS (252 KB)
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- Portuguese - PT (252 KB)
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取扱説明書 (2242 KB)
参考文献
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
Mivelsiran 関連分類
HY-177646 関連分類
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