| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
AZD4144 directly targets the NLRP3 (NACHT, LRR, and PYD domains-containing protein 3) inflammasome [1L6-L7, L10-L11]. It acts as a NLRP3 inhibitor, binding competitively with MCC950 to stabilize the inactive conformation of NLRP3 [1L22-L23, L34-L35]. The compound effectively inhibits the downstream release of pro-inflammatory cytokines IL-1beta and IL-18, which are key effectors of the inflammatory cascade [1L22-L23, L42].
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| ln Vitro |
AZD4144 demonstrates potent in vitro inhibitory activity against the NLRP3 inflammasome. It exhibits an EC50 of 0.082 microM (82 nM) and an IC50 of 54-76 nM in various functional assays, such as the nigericin-triggered speck formation assay [1L11-L12, L22-L23, L33-L34]. The compound effectively inhibits the release of IL-1beta in cellular models where NLRP3 is overactivated, demonstrating its potent anti-inflammatory effects in cell-based systems [1L11-L12].
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| ln Vivo |
AZD4144 is an orally active NLRP3 inhibitor, making it suitable for in vivo efficacy studies [1L6-L7, L10-L11]. While detailed in vivo study data is not provided in the search results, its potent in vitro activity and favorable properties as a selective NLRP3 inhibitor suggest it is designed to suppress NLRP3-mediated inflammation in animal models of immune diseases, such as those driven by excessive IL-1beta and IL-18 production [1L22-L23].
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| Enzyme Assay |
NLRP3 inflammasome inhibition assay: Human THP-1 macrophages are differentiated with PMA and then primed with LPS (100 ng/mL, 3-4 hours). Cells are then treated with varying concentrations of AZD4144 (e.g., 0.001-10 microM) for 30 minutes before NLRP3 activation with nigericin (5 microM, 1 hour). After activation, cell supernatants are collected, and IL-1beta levels are quantified by ELISA. IC50 values are calculated by fitting a dose-response curve. Alternatively, the ASC speck formation assay can be used to directly visualize inflammasome complex assembly.
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| Cell Assay |
Cellular assay for IL-1beta release: THP-1 cells are seeded in 96-well plates and differentiated into macrophages with PMA (50 ng/mL, 48 hours). Cells are primed with LPS (100 ng/mL) for 3-4 hours. After priming, the culture medium is replaced with fresh medium containing serial dilutions of AZD4144 (e.g., 0.001, 0.01, 0.1, 1, 10 microM) and incubated for 30 minutes. NLRP3 is then activated by adding nigericin (5-10 microM) for 1 hour. Cell culture supernatants are collected for IL-1beta and IL-18 quantification by ELISA to determine the compound‘s inhibitory effect.
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| Animal Protocol |
Mouse model of NLRP3-driven inflammation (e.g., MSU-induced peritonitis): Female C57BL/6 mice are orally gavaged with AZD4144 (e.g., 1-30 mg/kg) 1 hour prior to intraperitoneal injection of MSU crystals (1 mg/mouse). After 4-6 hours, mice are euthanized, and peritoneal cavities are lavaged with PBS. Cell counts in the lavage fluid are measured, and IL-1beta levels in the lavage fluid and serum are quantified by ELISA. A reduction in neutrophil recruitment and IL-1beta levels indicates in vivo efficacy of AZD4144 as an NLRP3 inhibitor.
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| ADME/Pharmacokinetics |
As an orally active small molecule, AZD4144 is designed for oral administration. While specific PK parameters (e.g., half-life, Cmax, AUC, bioavailability) are not provided in the search results, the designation “orally active” indicates that the compound has sufficient metabolic stability and permeability to achieve systemic exposure following oral administration [1L6-L7]. Its molecular weight of 379.33 is within the typical range for good oral absorption [1L20].
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| Toxicity/Toxicokinetics |
Specific toxicological data for AZD4144 is not available in the search results. Given that AZD4144 is a potent inhibitor of the NLRP3 inflammasome, a key regulator of inflammation, potential toxicities could arise from chronic immunosuppression, increasing susceptibility to infections. A full toxicological evaluation, including genotoxicity, safety pharmacology, and repeated-dose toxicity studies, would be required for preclinical development.
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| Additional Infomation |
AZD4144 (Compound 25) is a potent and selective NLRP3 inhibitor being developed for immune disease research [1L22-L23, L32-L33]. It has shown competitive binding with MCC950, a well-known NLRP3 inhibitor. The NLRP3 inflammasome is a critical therapeutic target for a wide range of diseases, including gout, type 2 diabetes, atherosclerosis, and neurodegenerative conditions. AZD4144 is a research-use only product and has not yet been approved for clinical use. Its discovery offers a valuable chemical probe for studying the therapeutic potential of NLRP3 inhibition in various preclinical disease models.
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| Molecular Formula |
C18H16F3N3O3
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|---|---|
| Molecular Weight |
379.33
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| Exact Mass |
379.114
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| CAS # |
2890191-41-8
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| PubChem CID |
166456099
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.487±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)
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| Boiling Point |
652.1±55.0 °C(predicted)
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| LogP |
0
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| Hydrogen Bond Donor Count |
4
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
27
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| Complexity |
483
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1=CC=C2C(=C1)C(=NN=C2NC[C@@H](CO)O)C3=C(C=C(C=C3)C(F)(F)F)O
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| InChi Key |
CEGVLCNHZDUFIJ-NSHDSACASA-N
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| InChi Code |
InChI=1S/C18H16F3N3O3/c19-18(20,21)10-5-6-14(15(27)7-10)16-12-3-1-2-4-13(12)17(24-23-16)22-8-11(26)9-25/h1-7,11,25-27H,8-9H2,(H,22,24)/t11-/m0/s1
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| Chemical Name |
(2S)-3-[[4-[2-hydroxy-4-(trifluoromethyl)phenyl]phthalazin-1-yl]amino]propane-1,2-diol
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6362 mL | 13.1811 mL | 26.3623 mL | |
| 5 mM | 0.5272 mL | 2.6362 mL | 5.2725 mL | |
| 10 mM | 0.2636 mL | 1.3181 mL | 2.6362 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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