ISIS 626112
ISIS 626112 (ION-626112) is a blood-brain barrier-permeable MOE-gapmer antisense oligonucleotide and also an inhibitor of the Malat1 long non-coding RNA. ISIS 626112 triggers RNase H1-mediated cleavage and degradation of complementary Malat1 RNA. ISIS 626112 dose-dependently reduces Malat1 RNA levels in all tested central nervous system regions and major central nervous system cell types in mice, with glial cells showing higher sensitivity than neurons.
For research use only. We do not sell to patients.
- CAS No.: 2091995-55-8
- Molecular Weight:7152.75
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
In Vivo
ISIS 626112 (administered via a single intraspinal bolus injection at doses of 10–3000 μg) achieves widespread distribution across most regions of the rat central nervous system and reduces Malat1 RNA levels in a dose-dependent manner, with the striatum showing the least pronounced target downregulation[2].
ISIS 626112 (25 mg; intrathecal injection; single bolus on Days 1, 14 and 28) achieves widespread distribution across most central nervous system regions and ganglia in non-human primates, and reduces Malat1 RNA levels by 80%-90%[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6J (female, wild-type)[2]
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Dosage:1 μg, 3 μg, 10 μg, 30 μg, 100 μg, 300 μg, 700 μg
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Administration:i.c.v.; single bolus injection
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Result:Reduced Malat1 RNA dose-dependently across all tested CNS regions (spinal cord, brainstem, cortex, cerebellum, hippocampus, thalamus, hypothalamus, striatum), with reduction correlated to ASO tissue concentration.
Achieved widespread Malat1 RNA reduction across most CNS regions at 300 μg; in the cerebellum, reduced Malat1 RNA efficiently in Purkinje cells and the molecular layer but minimally in the granular layer.
Reduced Malat1 RNA dose-dependently in isolated cortical cell types, with ED50 values of 17 μg for astrocytes, 34 μg for oligodendrocytes, 71 μg for microglia, and 206 μg for neurons.
Showed no induction of microglial (Aif1) or astrocyte (Gfap) activation.
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Animal Model:Sprague-Dawley (male, adult, 0.25-0.35 kg, wild-type)[2]
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Dosage:10 μg, 30 μg, 100 μg, 300 μg, 1000 μg, 3000 μg
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Administration:i.t.; single bolus injection
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Result:Reduced Malat1 RNA dose-dependently across all tested CNS regions (lumbar cord, thoracic cord, cervical cord, multiple cortical regions, brainstem, thalamus, striatum, cerebellum, hippocampus, hypothalamus), with reduction correlated to ASO tissue concentration.
Achieved only 50% Malat1 RNA reduction in the striatum even at the highest dose tested.
Reduced Malat1 RNA efficiently in the cerebellum's molecular and Purkinje cell layers but modestly in the granular layer.
Showed no induction of microglial (Aif1) or astrocyte (Gfap) activation.
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Animal Model:Cynomolgus (female, adult, 2.4 kg, wild-type)[2]
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Dosage:25 mg
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Administration:i.t.; bolus injection on Day 1, 14, and 28
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Result:Achieved widespread ASO distribution across the CNS, with the highest tissue concentrations in cortical regions, followed by spinal cord (proximal: 25 μg/g, distal: 13 μg/g), pons, medulla, hippocampus, thalamus, amygdala, and cerebellar cortex; lower concentrations were seen in globus pallidus, caudate, and putamen.
Reduced Malat1 RNA by 80-90% in most CNS regions, consistent with ASO tissue concentration.
Reduced Malat1 RNA at the cellular level even in regions with lower whole-tissue ASO accumulation (globus pallidus, caudate, putamen).
Detected ASO accumulation and Malat1 RNA reduction in trigeminal ganglion and dorsal root ganglia at cervical, thoracic, and lumbar levels.
Showed no induction of microglial (Aif1) or astrocyte (Gfap) activation.
Chemical Information
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CAS No. 2091995-55-8
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Molecular Weight 7152.75
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SMILES
[ISIS 626112]
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Synonyms
ION-626112
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
ISIS 626112 Related Classifications
HY-159693 Related Classifications
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