CNB-001
CNB-001 is a potent and orally active 5-lipoxygenase (5-LOX) inhibitor. CNB-001 can decreases 5-LOX expression and increase proteasome activity. CNB-001 can inhibit accumulation of soluble Amyloid-β and ubiquitinated aggregated proteins. CNB-001 can inhibit apoptosis, ROS production and stabilize mitochondrial membrane potential. CNB-001 can reduce insulin resistance and increase glucose uptake. CNB-001 also exhibits anti-ischemic, anti-inflammatory effects. CNB-001 can be used for the researches of inflammation, neurological and metabolic disease, such as Alzheimer's disease, stroke and diabetes.
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- No. CAS: 1019110-87-2
- Fòrmula: C27H24N2O4
- Peso molecular:440.49
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Almacenamiento:
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
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Actividad biológica
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Chemical Information
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Actividad biológica
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5-LOX 70 nM (IC50) |
15-LOX |
CNB-001 (1 μM, 24-96 h) inhibits and promotes the clearance of Aβ aggregation in MC65 cells[1].
CNB-001 (1 μM, 48 h) activates three proteasome activities (chymotrypsin-like, trypsin-like, caspase-like) and degrades Aβ in MC65 cells[1].
CNB-001 (1 μM, 1-24 h) induces eIF2α (Ser51) phosphorylation and increases ATF4 expression in MC65 cells[1].
CNB-001 (1 μM, 1-24 h) inhibits 5-lipoxygenase (5-LOX, IC50 = 70 nM) and increases S523 phosphorylation and decreases S271 phosphorylation of 5-LOX in MC65 cells[1].
CNB-001 inhibits leukotriene B4 (LTB4) production in human peripheral blood mononuclear lymphocytes (PBML) with an IC50 of 0.076 μM[2].
CNB-001 (0-2 μM) inhibits 15-LOX in rabbit reticulocytes[2].
NB-001 (0.5-15 μM, 24 h) exhibits a half-toxic concentration (TC50) of 15.3 μM in quiescent C2C12 myotubes[3].
CNB-001 (1 μM, 12 h) reverses Palmitic acid (HY-N0830)-induced insulin resistance and restores insulin-stimulated glucose uptake in C2C12 myotubes[3].
CNB-001 protects SK-N-SH human neuroblastoma cells against Rotenone (HY-B1756)-induced neurotoxicity by inhibiting intracellular ROS generation, apoptosis and stabilizing mitochondrial membrane potential[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:MC65 cells
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Concentration:1 μM
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Incubation Time:1, 2, 4 and 6 h
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Result:Increased S523 phosphorylation and decreases S271 phosphorylation of 5-LOX.
CNB-001 (500 mg/kg, p.o., 30 mins before Aβ1-42 injection) completely reverses the contextual memory impairment in mice injected with Aβ1-42[1].
CNB-001 (5-50 mg/kg, i.v., 5 or 60 mins post-embolization) improves behavioral deficits in New Zealand white rabbits with embolic stroke[2].
CNB-001 (10 mg/kg, i.v., 5 mins after MCAO) reduces infarct expansion in cynomolgus monkeys with permanent middle cerebral artery occlusion (MCAO)[2].
CNB-001 (40 mg/kg, i.p., daily except weekends for 20-22 weeks) alleviates high-fat diet-induced obesity and insulin resistance in C57BL/6J mice[3].
CNB-001 (24 mg/kg, i.p., daily from day 1 to day 7) mitigates motor impairments and neurotoxicity in MPTP-induced Parkinson’s disease (PD) mice[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:APPswe/PS1E9 transgenic models[1]
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Dosage:25 mg/kg diet
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Administration:Orally administration, daily for 6 months
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Result:Increased arm alternation choices.
Increased eIF2α phosphorylation, ATF4 and HSP90 expression in the hippocampus.
Reduced soluble Aβ1-42 (50%) and ubiquitinated aggregated proteins.
Increased the expression of synapse-associated proteins (phosphorylated synapsin-1, Pro-BDNF, Homer1).
Decreased the expression of clusterin and 5-LOX (>40%).
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Animal Model:New Zealand white rabbits with embolic stroke[2]
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Dosage:5-50 mg/kg 1 h post-embolization and 10 mg/kg 5 min post-embolization
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Administration:Intravenously injection
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Result:Increased P50 (clot burden causing 50% neurological dysfunction) by 74%.
Decreased COX-2 and 5-LOX expression, and increased BDNF levels in ipsilateral cortical tissues.
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Animal Model:High-fat diet-induced obesity and insulin resistance in C57BL/6J mice models[3]
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Dosage:40 mg/kg
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Administration:Intraperitoneally injection, daily except weekends for 20-22 weeks
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Result:Reduced body weight gain (without altering food intake).
Decreased serum triglyceride and interleukin-6 (IL-6) levels.
Improved glucose tolerance (lowers IPGTT AUC) and insulin sensitivity (lowers IPITT AUC).
Restored insulin-stimulated glucose uptake in gastrocnemius muscle.
Upregulated insulin signaling molecules (p-IR, p-Akt) and downregulates protein-tyrosine phosphatase 1B (PTP1B) and phospho-eIF2α in skeletal muscle.
Attenuated hepatic steatosis (reduces liver triglycerides and Oil Red O-stained fat droplets), and increased energy expenditure (without changing respiratory exchange ratio, RER).
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Animal Model:MPTP-induced Parkinson’s disease (PD) mice[4]
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Dosage:24 mg/kg
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Administration:Intraperitoneally injection, daily from day 1 to day 7
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Result:Reduced runway crossing time and foot slip errors in the narrow beam test.
Shortened fixed posture duration and reduced latency to shift four limbs.
Restored striatal dopamineand its metabolites (DOPAC, HVA) levels.
Decreased nitrite and citrulline accumulation.
Downregulated pro-inflammatory factors (TNF-α, IL-1β, IL-6, iNOS, GFAP, COX-2) and pro-apoptotic markers (Bax, cytochrome C, cleaved caspase-3).
Upregulated anti-apoptotic Bcl-2, and increased dopamine transporter (DAT) immunoreactivity in the substantia nigra (SN) and striatum (ST).
Chemical Information
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No. CAS 1019110-87-2
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Appearance Solid
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Peso molecular 440.49
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Fòrmula C27H24N2O4
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Color White to off-white
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SMILES
OC1=CC=C(C=C1OC)/C=C/C2=NN(C3=CC=CC=C3)C(/C=C/C4=CC(OC)=C(O)C=C4)=C2
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Pureza y Documentación
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Ficha de datos (281 KB)
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SDS (252 KB)
- Français - FR (252 KB)
- Deutsch - DE (252 KB)
- Norwegian - NO (252 KB)
- Español - ES (252 KB)
- Swedish - SV (252 KB)
- Italian - IT (252 KB)
- Korean - KR (252 KB)
- Portuguese - PT (252 KB)
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Instrucciones de manejo (2659 KB)
Referencias
[1]. Valera E, et al. Modulation of 5-lipoxygenase in proteotoxicity and Alzheimer's disease. J Neurosci. 2013 Jun 19;33(25):10512-25. [Content Brief]
[2]. Lapchak PA, et al. CNB-001, a pleiotropic drug is efficacious in embolized agyrencephalic New Zealand white rabbits and ischemic gyrencephalic cynomolgus monkeys. Exp Neurol. 2019 Mar;313:98-108. [Content Brief]
[3]. Panzhinskiy E, et al. Novel curcumin derivative CNB-001 mitigates obesity-associated insulin resistance. J Pharmacol Exp Ther. 2014 May;349(2):248-57. [Content Brief]
[4]. Jayaraj RL, et al. CNB-001, a novel pyrazole derivative mitigates motor impairments associated with neurodegeneration via suppression of neuroinflammatory and apoptotic response in experimental Parkinson's disease mice. Chem Biol Interact. 2014 Sep 5;220:149-57. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
CNB-001 Related Classifications
HY-158204 Related Classifications
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