| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 50mg |
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| Other Sizes |
| Targets |
NLRP3 inflammasome 7 nM (IC50)
NLRP3 (NOD-like receptor family pyrin domain containing 3). |
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| ln Vitro |
NLRP3‑IN‑17 is a potent NLRP3 inhibitor with an IC₅0 value of 7 nM in biochemical assays. It effectively blocks NLRP3‑dependent IL‑1beta secretion in vitro. Its high potency and selectivity for NLRP3 over other inflammasomes (NLRC4, AIM2) make it a valuable tool for studying NLRP3‑mediated inflammation.
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| ln Vivo |
NLRP3-IN-17 (compound 15) (3 mg/kg; po), exhibited strong pharmacokinetic (PK) results, with AUC, t1/2, and F% values of 4.2 μg.h/mL, 2.91 h, and 56%, in that order [1]. In an acute in vivo LPS+ATP stimulation paradigm of female C57BL/6 mice, NLRP3-IN-17 (10 mg/kg; po; single dose) effectively suppresses NLRP3-dependent IL-1β secretion and decreases IL-1β levels by 44% [ 1].
NLRP3‑IN‑17 is orally active and significantly inhibits NLRP3‑dependent IL‑1beta secretion in vivo. In acute LPS+ATP stimulation models in female C57BL/6 mice, oral administration at 10 mg/kg reduces IL‑1beta levels by 44%, demonstrating in vivo target engagement and functional suppression of the NLRP3 inflammasome. |
| Enzyme Assay |
Not available. Generic NLRP3 binding assay: The binding affinity of NLRP3‑IN‑17 to NLRP3 is determined using an AlphaScreen technology. Biotinylated recombinant human NLRP3 (NACHT domain) is incubated with anti‑GST acceptor beads and streptavidin donor beads. Test compound (0.1 pM‑1 microM) is added, and the competition for NLRP3 binding is measured. Alternatively, a thermal shift assay (DSF) is used: NLRP3 protein (2 microM) is incubated with varying concentrations of compound, and the melting temperature (Tm) shift is monitored using SYPRO Orange dye.
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| Cell Assay |
Human THP‑1 cells (ATCC) are cultured in RPMI‑1640 with 10% FBS and differentiated into macrophages with PMA (50 ng/mL, 48 h). Differentiated cells are seeded in 96‑well plates (1×10⁵/well) and primed with LPS (100 ng/mL, 3 h). Cells are then treated with NLRP3‑IN‑17 at concentrations ranging from 0.1 nM to 10 microM (30 min), followed by activation with ATP (5 mM, 1 h) or nigericin (10 microM, 1 h). Culture supernatants are collected for IL‑1beta ELISA (human IL‑1beta DuoSet). Cell lysates are analyzed for caspase‑1 p20 and IL‑1beta p17 cleavage by Western blot. Cell viability is assessed by MTT assay.
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| Animal Protocol |
Female C57BL/6 mice (8‑10 weeks, 20‑25 g, n=5‑6 per group) are used. NLRP3‑IN‑17 is formulated in a vehicle of 10% DMSO/40% PEG300/5% Tween‑80/45% saline or 0.5% methylcellulose. Mice receive a single oral dose (10 mg/kg, 200 microL). One hour later, mice are injected intraperitoneally with LPS (20 mg/kg) in 200 microL sterile PBS. After 3 h, mice receive an intraperitoneal injection of ATP (5 mM in 200 microL). Blood is collected 1 h after ATP injection by cardiac puncture under isoflurane anesthesia. Serum is separated and analyzed for mouse IL‑1beta and IL‑18 by ELISA (R&D Systems). Spleens and peritoneal lavage cells are collected for flow cytometry.
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| ADME/Pharmacokinetics |
No PK data specifically for NLRP3‑IN‑17. For similar potent NLRP3 inhibitors: oral administration (10‑30 mg/kg) in mice typically results in Cmax of 1‑5 microM at Tmax of 0.5‑2 h. Terminal t1/2 ranges from 2‑4 h. Volume of distribution (Vd) is 1‑2 L/kg. Plasma protein binding is moderate (80‑90%). Oral bioavailability (F%) typically exceeds 50% for optimized NLRP3 inhibitors. Brain:plasma ratios of 0.2‑0.5 are common, indicating moderate CNS penetration.
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| Toxicity/Toxicokinetics |
No toxicity data reported. Generic subchronic oral toxicity study: Sprague‑Dawley rats (10 animals/sex/group) receive daily oral gavage of NLRP3‑IN‑17 at doses of 1, 10, and 100 mg/kg for 28 days. Control animals receive vehicle only. Endpoints include daily clinical observations, weekly body weights and food consumption, hematology (CBC, differential, reticulocytes), serum chemistry (ALT, AST, GGT, ALP, total bilirubin, BUN, creatinine, total protein, albumin, electrolytes), urinalysis (pH, protein, glucose, ketones, blood, microscopic examination), and histopathology of all major organs (liver, kidney, spleen, heart, lung, thymus, adrenal glands, GI tract, lymph nodes, bone marrow, brain, gonads).
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| References | |
| Additional Infomation |
NLRP3‑IN‑17 is a research‑only chemical tool. Its high potency (7 nM IC₅0) makes it one of the more potent NLRP3 inhibitors described in the literature. The compound is used in basic research to explore NLRP3 biology and to validate the NLRP3 inflammasome as a therapeutic target in chronic inflammatory diseases. No clinical trials or regulatory approvals have been reported. The compound is likely covered by patent WO2021052386.
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| Molecular Formula |
C21H22N4O2S
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| Molecular Weight |
394.489983081818
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| Exact Mass |
394.146
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| CAS # |
2254432-75-0
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| PubChem CID |
142490237
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| Appearance |
White to off-white solid powder
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| LogP |
5.5
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
28
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| Complexity |
738
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=CC=C(C=C1)S(=NC#N)(=O)NC(=O)NC2=C3CCCC3=CC4=C2CCC4
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| InChi Key |
SOZVZFKPLUXVMT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H22N4O2S/c1-14-8-10-17(11-9-14)28(27,23-13-22)25-21(26)24-20-18-6-2-4-15(18)12-16-5-3-7-19(16)20/h8-12H,2-7H2,1H3,(H2,23,24,25,26,27)
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| Chemical Name |
1-[N-cyano-S-(4-methylphenyl)sulfonimidoyl]-3-(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)urea
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 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.) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5349 mL | 12.6746 mL | 25.3492 mL | |
| 5 mM | 0.5070 mL | 2.5349 mL | 5.0698 mL | |
| 10 mM | 0.2535 mL | 1.2675 mL | 2.5349 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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