RN-0001
RN-0001 is an inhibitor of Calcineurin and cyclophilin (Cyp), with Ki values of 4.1 nM and 12.0 nM against CypA and CypD, respectively, and an EC50 of 916 nM for CypD. RN-0001 binds directly to CypD, inhibits the peptidyl-prolyl cis-trans isomerase activities of CypD and CypA, and prevents CypD-dependent mitochondrial permeability transition pore opening. RN-0001 improves mitochondrial function, reduces ROS production, inhibits the expression of lipogenic markers, blocks the nuclear translocation of NF-κB p65, and decreases the release of activated caspase-3 and cytochrome c. RN-0001 can be used in the research of alcohol-associated liver disease.
For research use only. We do not sell to patients.
- CAS No.: 252731-57-0
- Formula: C66H120N12O13
- Molecular Weight:1289.73
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
Description
In Vitro
RN-0001 (multiple concentrations; 30 min ambient temperature, 15 min 30°C reaction) exhibits weak direct calcineurin inhibition (IC50 = 2276 nM) and moderately enhanced inhibition when complexed with cyclophilin A (IC50 = 1551 nM) in a cell-free assay[1].
RN-0001 (multiple concentrations) preserves mitochondrial calcium retention capacity with an EC50 of 916 nM in a cell-free isolated mitochondrial assay[1].
RN-0001 (multiple concentrations) has reduced immunosuppressive activity, inhibiting IL-2 release with an EC50 of 347.90 nM in a cell-based immune cell assay[1].
RN-0001 (0.01-10 μM; 24 h) improves viability in ethanol-injured AML12 hepatocytes (IC50 = 102.7 μM) and RAW264.7 macrophages (IC50 = 60.73 μM) in a concentration-dependent manner, with superior efficacy to Debio-025 at matching doses[1].
RN-0001 (0.01-10 μM; 24 h) concentration-dependently reduces LDH release, apoptosis, and aberrant expression of lipogenic, inflammatory, oxidative stress, and apoptotic proteins in ethanol-injured AML12 hepatocytes[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:AML12 cells
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Concentration:0.01, 0.1, 1 and 10 μM
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Incubation Time:24 h
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Result:Reduced cell apoptosis.
Parmacokinetics
In Vivo
RN-0001 (10 mg/kg; i.p.; once every 2 days; for 90 consecutive days) is well tolerated and causes no adverse effects in healthy mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6J (male, 7 weeks old, NIAAA chronic-plus-binge ethanol feeding model)[1]
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Dosage:10 mg/kg
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Administration:i.p.; daily
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Result:Partially reversed alcohol-induced weight loss.
Reduced serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides (TG), and total cholesterol (TC).
Decreased serum pro-inflammatory cytokines TNF-α and IL-6.
Normalized liver weight/body weight ratio.
Reduced liver free fatty acid (FFA) and TG levels.
Decreased hepatic fat droplet accumulation and macrophage infiltration, resulting in a lower NAFLD Activity Score (NAS).
Reversed aberrations in key proteins involved in mitochondrial function (DRP1, FIS1, MFN1, MFN2, OPA1), oxidative stress (CYP2E1, iNOS), antioxidation (p-NRF2, NRF2, SOD1, CAT), and apoptosis (cleaved caspase-3, Cyto C, Bcl2, BAX).
Reduced mitochondrial swelling post-ethanol exposure.
- RNA extraction experimental
- Cytoplasmic-Nuclear Fractionated Protein Extraction
- Mitochondrial membrane-potential fluorescent assay
- ROS/oxidative-stress fluorescent staining
- Mitochondrial membrane-potential and mitochondrial mass staining
- Transepithelial/transendothelial electrical resistance assay
- Apoptosis Solutions
- Research Protocol for Inflammation-related Diseases
Chemical Information
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CAS No. 252731-57-0
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Molecular Weight 1289.73
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Formula C66H120N12O13
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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)
Keywords
- RN-0001
- 252731-57-0
- RN0001
- RN 0001
- Cyclophilin
- Reactive Oxygen Species (ROS)
- NF-κB
- Caspase
- Apoptosis
- Nuclear factor-κB
- Nuclear factor-kappaB
- NF-κB p65
- AML12 hepatocytes
- alcohol-associated liver disease
- reactive oxygen species
- peptidyl-prolyl cis-trans isomerase
- CypA
- mitochondrial permeability transition pore
- cytochrome c
- CypD
- cleaved caspase-3
- Inhibitor
- inhibitor
- inhibit