AZD8233
AZD8233 is an orally active antisense oligonucleotide targeting PCSK9 mRNA. AZD8233 highly specifically reduces PCSK9 mRNA. AZD8233 lowers LDL cholesterol. AZD8233 can be used in research on dyslipidemia.
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- CAS No.: 2604215-74-7
- Masse moléculaire:6920.84
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Activité biologique
Description
In Vitro
AZD8233 is highly specific to reducing PCSK9 mRNA in human cells, showing ≥10-fold IC50 selectivity over all other transcripts[1].
AZD8233 (5-134 nM; 8 h; 12 h post-transfection) silenced PCSK9 comparably to P-12c in human HepG2 cells at 5 nM, while P-12c exhibited markedly superior efficiency at higher doses[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:human HepG2 cells
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Concentration:5, 15, 44, and 134 nM
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Incubation Time:8 h (incubation); 12 h post-transfection (RNA analysis)
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Result:No numerical PCSK9 silencing value for AZD8233 alone was reported.
P-12c displayed comparable PCSK9 silencing efficacy to AZD8233 at 5 nM, while P-12c exhibited markedly superior efficiency at 15, 44, and 134 nM.
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:heterozygous human PCSK9 transgenic (huPCSK9 Tg) (male, 5 months old)[1]
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Dosage:0.25, 0.5, 1, 2.5, and 5 mg/kg
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Administration:s.c.; days 1, 5, 8, 15, and 23
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Result:Liver exposure increased dose-dependently.
Liver exposure of 4 µg/g (3 and 5 µg/g; 5th and 95th percentiles) was predicted to result in 80% reduction in plasma PCSK9.
A dose of AZD8233 0.5 mg/kg was required to reduce PCSK9 by 80%.
The liver exposure-PCSK9 model estimated IC50 = 2.0 µg/g (1.4 and 2.9 µg/g; 5th and 95th percentiles) and Hill coefficient h = 2.2 (1.6 and 3.8).
Concomitant dose-dependent reductions of human plasma PCSK9 and LDL cholesterol were observed.
Essai clinique
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 2604215-74-7
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Masse moléculaire 6920.84
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SMILES
[AZD8233]
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocole
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RNA extraction experimental
By lysing cells, releasing RNA, and removing impurities such as proteins and DNA, high-purity RNA products are finally obtained. The commonly used traditional method is the guanidine isothiocyanate/phenol/chloroform method (Trizol), which is suitable for a variety of animal materials including animal tissues, microorganisms, cultured cells, etc., and most plant materials.
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Research Protocol for Metabolic Diseases
AMP-activated protein kinase, AMPK, is a conserved cellular energy sensor that responds to reduced cellular energy status and coordinates metabolism by increasing ATP-generating catabolic pathways while suppressing ATP-consuming anabolic processes. In metabolic disease research, the AMPK pathway is experimentally relevant because it regulates hepatic lipid synthesis, fatty acid oxidation, glucose production, skeletal-muscle glucose disposal, mTORC1-linked biosynthesis, autophagy, mitochondrial homeostasis, and whole-body energy balance. The central pathway logic is that energy stress, metformin, exercise-like stimulation, or direct AMPK activators increase AMPKα Thr172 phosphorylation and downstream substrate phosphorylation, including ACC and RAPTOR. Phosphorylation of ACC suppresses lipogenesis and supports fatty acid oxidation, whereas phosphorylation of RAPTOR suppresses mTORC1 signaling and links cellular energy status to growth and protein synthesis control. The pathway is linked
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)