| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 25mg | |||
| Other Sizes |
Purity: =98.59%
| Targets |
NLRP3[1]
NLRP3 (NOD-like receptor family pyrin domain containing 3). |
|---|---|
| ln Vitro |
Usnoflast inhibits NLRP3 inflammasome activation in vitro, blocking the release of IL‑1beta from LPS‑primed and ATP‑ or nigericin‑stimulated macrophages. It does not directly inhibit caspase‑1 or NLRC4 inflammasome, demonstrating selectivity for NLRP3.
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| ln Vivo |
Usnoflast (ZYIL1) is orally active and suppresses NLRP3 inflammasome activation in vivo. In mouse models of NLRP3‑driven inflammation (e.g., LPS‑induced systemic inflammation or MSU crystal‑induced peritonitis), oral administration reduces IL‑1beta levels in serum and peritoneal lavage fluid, and attenuates neutrophil infiltration.
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| Enzyme Assay |
Not available. Generic NLRP3 binding assay: HEK293T cells are co‑transfected with NLRP3, ASC, and pro‑caspase‑1 expression plasmids. Cell lysates are incubated with test compound (0‑100 microM) in reaction buffer, and ASC oligomerization or NLRP3‑ASC interaction is assessed by co‑immunoprecipitation or proximity ligation assay. Alternatively, purified NLRP3 protein is used in surface plasmon resonance (SPR) to measure direct binding affinity.
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| Cell Assay |
Mouse primary bone marrow‑derived macrophages (BMDMs) or THP‑1 cells are seeded in 96‑well plates, primed with LPS (100 ng/mL, 3‑4 h), then treated with test compound (0.01‑10 microM) for 30 min, followed by stimulation with NLRP3 activators: ATP (5 mM, 1 h) or nigericin (10 microM, 1 h). Supernatants are collected and IL‑1beta levels are quantified by ELISA. Cell lysates are analyzed for caspase‑1 p20 cleavage by Western blot to confirm inflammasome inhibition.
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| Animal Protocol |
Usnoflast is administered orally to C57BL/6 mice (8‑10 weeks) at doses of 10‑50 mg/kg in a suitable vehicle. For MSU crystal‑induced peritonitis model: mice receive intraperitoneal injection of MSU crystals (1 mg) 30 min after compound administration. After 4‑6 h, peritoneal lavage fluid is collected for neutrophil count, IL‑1beta, and IL‑18 ELISA. For LPS‑induced systemic inflammation: mice receive LPS (5 mg/kg, i.p.) after oral compound; serum is collected 4‑6 h later for cytokine analysis.
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| ADME/Pharmacokinetics |
No PK data specifically for Usnolast. For similar NLRP3 inhibitors: Oral administration (10‑20 mg/kg) in mice yields Cmax around 1‑3 microM, Tmax 0.5‑2 h, and terminal t1/2 of 2‑4 h. Plasma protein binding is moderate (70‑90%). Oral bioavailability is typically >50% for optimized NLRP3 inhibitors. Brain penetration may be limited for many NLRP3 inhibitors due to efflux transporters.
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| Toxicity/Toxicokinetics |
No toxicity data specifically reported for Usnolast. For structurally related NLRP3 inhibitors, generic safety assessment includes: repeated oral dosing in rats (25‑200 mg/kg/day for 28 days) with monitoring of body weight, food consumption, hematology, serum chemistry (ALT, AST, creatinine, BUN), and histopathology (liver, kidney, spleen, heart, lung). Organ weight changes and signs of immunosuppression are key endpoints.
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| References | |
| Additional Infomation |
NLRP3 inflammasome inhibitors
Usnolast is a research‑stage NLRP3 inhibitor with no approved therapeutic indications. It is structurally classified as a substituted sulfonylurea derivative (patent WO2020148619). The compound may have potential in neuroinflammatory disorders due to its ability to suppress NLRP3 activation, but clinical development status remains unconfirmed. |
| Molecular Formula |
C21H29N3O3S
|
|---|---|
| Molecular Weight |
403.538264036179
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| Exact Mass |
403.192
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| CAS # |
2455519-86-3
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| PubChem CID |
154648184
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| Appearance |
White to off-white solid powder
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| LogP |
3.6
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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 |
4
|
| Heavy Atom Count |
28
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| Complexity |
712
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C[C@@]1(CCCN1C)/C=C/S(=O)(=O)NC(=O)NC2=C3CCCC3=CC4=C2CCC4
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| InChi Key |
HAMGPBKPACGWND-ZOXUKVPXSA-N
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| InChi Code |
InChI=1S/C21H29N3O3S/c1-21(10-5-12-24(21)2)11-13-28(26,27)23-20(25)22-19-17-8-3-6-15(17)14-16-7-4-9-18(16)19/h11,13-14H,3-10,12H2,1-2H3,(H2,22,23,25)/b13-11+/t21-/m1/s1
|
| Chemical Name |
1-[(E)-2-[(2R)-1,2-dimethylpyrrolidin-2-yl]ethenyl]sulfonyl-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 |
| 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 | 2.4781 mL | 12.3903 mL | 24.7807 mL | |
| 5 mM | 0.4956 mL | 2.4781 mL | 4.9561 mL | |
| 10 mM | 0.2478 mL | 1.2390 mL | 2.4781 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.
Link: https://clinicaltrials.gov/ct2/show/NCT07023835
Conditions:Amyotrophic Lateral Sclerosis (ALS)Link: https://clinicaltrials.gov/ct2/show/NCT05981040
Conditions:Amyotrophic Lateral SclerosisLink: https://clinicaltrials.gov/ct2/show/NCT05186051
Conditions:Cryopyrin Associated Periodic Syndrome
Title:A Clinical Study to Evaluate the Safety, Tolerability and Pharmacokinetics and Pharmacodynamics of ZYIL1 Following Oral Administration in Healthy Volunteers
Status:Completed
updateDate:2021-11-16
Ctid:NCT04972188
Link: https://clinicaltrials.gov/ct2/show/NCT04972188
Conditions:HealthyLink: https://clinicaltrials.gov/ct2/show/NCT04731324
Conditions:HealthyProducts are for research use only; We do not sell to patients
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