NT-0527
Based on 1 Customer Validation
NT-0527 is a selective, orally active, and brain-permeable NLRP3 inflammasome inhibitor. NT-0527 can specifically block the formation of the NLRP3 inflammasome, resulting in the reduction in the maturation and release of IL-1β, exhibit inhibition on CYP2C19. NT-0527 displays anti-inflammatory activity in the mouse LPS (HY-D1056) /ATP (HY-B2176)-induced peritonitis model. NT-0527 can be used for the research of neuroinflammatory disorders (Parkinson's disease, Alzheimer's disease, amyotrophic lateral sclerosis) and peripheral inflammatory disorders (type II diabetes, atherosclerosis, gout, etc.) associated with NLRP3 inflammasome.
For research use only. We do not sell to patients.
- Purity : 99.80%
- CAS No.: 2771019-10-2
- Formula: C17H14ClFN4O2
- Molecular Weight:360.77
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocols
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
Description
IC50 & Target
[1]|
IL-1β 0.79 μM (IC50) |
CYP2C19 |
NLRP3 inflammasome |
In Vitro
NT-0527 (0.001-10 μM; 90 min) disrupts the formation of NLRP3 inflammasome and reduces IL-1β release in a dose-dependent manner in human PBMCs, with IC50 values of 0.062 μM, 0.087 μM and 0.040 μM for ATP, MSU (HY-B2130A) and CPPD stimulation, respectively[1].
NT-0527 (0.01-100 μM; 3.5 h) inhibits IL-1β production in a dose-dependent manner with a mean IC50 of 0.79 μM in human whole blood [1].
NT-0527 (250 nM, 1 μM; 30 min) significantly inhibits NLRP3-mediated IL-1β release in human PBMCs, acting as a specific NLRP3 inhibitor[1].
NT-0527 (5 μM) exhibits high passive permeability and an efflux ratio in Caco-2 monolayer cell model, and is not a substrate for efflux transporters[1].
NT-0527 (1 μM) shows extremely low intrinsic clearance in human liver microsomes and cryopreserved hepatocytes, while moderate to high intrinsic clearance in rat and mouse liver microsomes and cryopreserved hepatocytes, showing the metabolic clearance rate in human liver is much slower than that in rats and mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Parmacokinetics
| Species | Dose | Route | MRT | CLplasma | Vss | AUC0-inf | F |
|---|---|---|---|---|---|---|---|
| Cynomolgus Monkey[1] | 3 mg/kg | i.v. | 3.9 h | 6.3 mL/min/kg | 1.4 L/kg | 8200 ng·h/mL | 104 % |
| Cynomolgus Monkey[1] | 3 mg/kg | p.o. | 3.9 h | 6.3 mL/min/kg | 1.4 L/kg | 9700 ng·h/mL | 104 % |
| Mice[1] | 3 mg/kg | i.v. | 0.25 h | 42 mL/min/kg | 0.63 L/kg | 1200 ng·h/mL | 39 % |
| Mice[1] | 3 mg/kg | p.o. | 0.25 h | 42 mL/min/kg | 0.63 L/kg | 470 ng·h/mL | 39 % |
| Pig[1] | 1 mg/kg | i.v. | / | / | / | / | / |
| Pig[1] | 2 mg/kg | p.o. | / | / | / | / | / |
| Rat[1] | 3 mg/kg | i.v. | 0.58 h | 10 mL/min/kg | 0.36 L/kg | 4800 ng·h/mL | 50 % |
| Rat[1] | 3 mg/kg | p.o. | 0.58 h | 10 mL/min/kg | 0.36 L/kg | 2400 ng·h/mL | 50 % |
In Vivo
NT-0527 (10 mg/kg; oral gavage; single administration; 24 h) achieves an almost even distribution between blood and cerebrospinal fluid[1].
NT-0527 (1-100 mg/kg; oral gavage) dose-dependently inhibits peritoneal IL-1β production with significant effect at 10 mg/kg[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Male non-naïve cynomolgus monkeys were administered formulated in 0.5% methocel (400cp) and 0.2% Tween 80 in purified water[1].
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Dosage:10 mg/kg
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Administration:Oral gavage (p.o.); single administration; 24 h
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Result:Achieved an almost even distribution between blood and cerebrospinal fluid (CSF), demonstrating efficient central nervous system (CNS) penetration.
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Animal Model:Male SD rats (fed) were subjected to non-recovery anaesthesia and cannulated at the right carotid artery for hemi-brain perfusion[1].
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Dosage:5 μM
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Administration:Carotid artery perfusion; single administration; 0.25-0.5 min
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Result:Exhibited high brain permeability, which was significantly higher than the low-permeability sulfonylurea NLRP3 inhibitors CRID3 (0.09 μM) (HY-12815) and emlenoflast (0.25 μM) (HY-137245); the permeability was higher than the high-permeability control diazepam (4.3 μM).
- Cotton Pellet Granuloma
- Carrageenan-Induced Paw Edema
- Human pluripotent stem cell midbrain dopaminergic neuron differentiation
- Zymosan-Induced Peritonitis
- Research Protocol for Cardiovascular Diseases
- Research Protocol for Inflammation-related Diseases
- Research Protocol for Metabolic Diseases
- Pyroptosis Solutions
- Alzheimer’s Disease Modeling
Chemical Information
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CAS No. 2771019-10-2
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Appearance Solid
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Molecular Weight 360.77
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Formula C17H14ClFN4O2
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Color White to off-white
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SMILES
O=C1C2=CC=C(C=C2C3(CC3)CN1CC(NC4=NC=C(C=N4)F)=O)Cl
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month
Solvent & Solubility
In Vitro:
DMSO : 125 mg/mL (346.48 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Purity & Documentation
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Data Sheet (273 KB)
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SDS (252 KB)
- English - EN (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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Handling Instructions (2659 KB)
References
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.7718 mL | 13.8592 mL | 27.7185 mL | 69.2962 mL |
| 5 mM | 0.5544 mL | 2.7718 mL | 5.5437 mL | 13.8592 mL | |
| 10 mM | 0.2772 mL | 1.3859 mL | 2.7718 mL | 6.9296 mL | |
| 15 mM | 0.1848 mL | 0.9239 mL | 1.8479 mL | 4.6197 mL | |
| 20 mM | 0.1386 mL | 0.6930 mL | 1.3859 mL | 3.4648 mL | |
| 25 mM | 0.1109 mL | 0.5544 mL | 1.1087 mL | 2.7718 mL | |
| 30 mM | 0.0924 mL | 0.4620 mL | 0.9239 mL | 2.3099 mL | |
| 40 mM | 0.0693 mL | 0.3465 mL | 0.6930 mL | 1.7324 mL | |
| 50 mM | 0.0554 mL | 0.2772 mL | 0.5544 mL | 1.3859 mL | |
| 60 mM | 0.0462 mL | 0.2310 mL | 0.4620 mL | 1.1549 mL | |
| 80 mM | 0.0346 mL | 0.1732 mL | 0.3465 mL | 0.8662 mL | |
| 100 mM | 0.0277 mL | 0.1386 mL | 0.2772 mL | 0.6930 mL |
NT-0527 Related Classifications
HY-186072 Related Classifications
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Keywords
- NT-0527
- 2771019-10-2
- NT0527
- NT 0527
- NOD-like Receptor (NLR)
- Interleukin Related
- Cytochrome P450
- NLRP3 inflammasome inhibitor
- inhibition of IL-1β release
- inhibition of CYP2C19
- human peripheral blood mononuclear cells (PBMCs)
- human whole blood
- Caco-2 monolayer cells
- C57BL/6J mice
- SD rats
- cynomolgus monkeys
- Bama minipigs
- mouse LPS/ATP-induced peritonitis model
- rat in situ brain perfusion model
- cynomolgus monkey CSF exposure model
- Parkinson's disease
- Alzheimer's disease
- amyotrophic lateral sclerosis (ALS)
- type II diabetes
- atherosclerosis
- obesity
- gout
- asthma
- inflammatory bowel disease (IBD)
- Metabolic Disease
- Inhibitor
- inhibitor
- inhibit