ARI-809
ARI-809 (CP-744809) is a highly selective, orally active aldose reductase inhibitor with an IC50 of 1 nM. ARI-809 blocks excessive glucose flux through the polyol pathway. ARI-809 normalizes elevated sorbitol and fructose levels in sciatic nerve tissues of diabetic rat models, inhibits sorbitol accumulation in lens tissues, and brings elevated urinary albumin excretion close to normal. ARI-809 can be used in diabetes research.
For research use only. We do not sell to patients.
- CAS No.: 463976-07-0
- Formula: C13H9ClN2O4S
- Molecular Weight:324.74
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
In Vitro
ARI-809 (CP-744809) shows high selectivity for aldose reductase over related dehydrogenases, with the lowest off-target potency against aldehyde reductase (IC50 = 930 nM) and minimal activity against alcohol, fructose, and sorbitol dehydrogenases[1].
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 | Bioavailability | Cmax | T1/2 |
|---|---|---|---|---|---|
| Rat[1] | 2 mg/kg | p.o. | 98 % | 5 μg/mL | 26 h |
In Vivo
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:CD Sprague Dawley (male, 175-225 g, streptozotocin-induced)[1]
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Dosage:0.2 mg/kg (acute sciatic nerve sorbitol normalization); 0.8 mg/kg (acute sciatic nerve fructose normalization; chronic sciatic nerve sorbitol normalization); 4.0 mg/kg (chronic sciatic nerve fructose normalization)
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Administration:oral gavage; single doses at 4,7,24h post-streptozotocin (acute); once daily for 5 days (chronic)
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Result:Achieved an ED50 of 0.2 mg/kg for normalization of elevated sciatic nerve sorbitol levels in acute test.
Achieved an ED50 of 0.8 mg/kg for normalization of elevated sciatic nerve fructose levels in acute test.
Achieved an ED90 of 0.8 mg/kg for normalization of elevated sciatic nerve sorbitol levels in chronic test.
Achieved an ED90 of 4.0 mg/kg for normalization of elevated sciatic nerve fructose levels in chronic test.
Potently suppressed elevated lens sorbitol levels, with greater efficacy than comparator agents including zopolrestat.
Produced near-normalization of 2.5-fold elevated urinary albumin output in a diabetic rat model.
Chemical Information
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CAS No. 463976-07-0
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Molecular Weight 324.74
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Formula C13H9ClN2O4S
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SMILES
O=C1C=CC(S(=O)(C2=C(C)C3=CC(Cl)=CC=C3O2)=O)=NN1
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Synonyms
CP-744809
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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.
Protocols
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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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
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)