| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
NLRP3
NLRP3. |
|---|---|
| ln Vitro |
Selnolast inhibits NLRP3 inflammasome activation with high potency. In human THP‑1 macrophages, it blocks nigericin‑induced IL‑1beta secretion with sub‑micromolar IC₅0 values. It does not inhibit NLRC4 or AIM2 inflammasomes, demonstrating selectivity for the NLRP3 pathway.
|
| ln Vivo |
Selnolast shows in vivo efficacy in preclinical models of NLRP3‑driven inflammation. In mouse models of cryopyrin‑associated periodic syndromes (CAPS) and ulcerative colitis, oral administration reduces IL‑1beta levels, attenuates tissue inflammation, and improves disease scores. It is being investigated for systemic inflammatory diseases such as ulcerative colitis and chronic obstructive pulmonary disease.
|
| Enzyme Assay |
Not available. Generic NLRP3 inhibitor binding assay: NLRP3 protein is expressed and purified from E. coli or insect cells. A fluorescence polarization (FP) or TR‑FRET assay is used to measure displacement of a labeled probe from the NLRP3 NACHT domain. Alternatively, binding affinity (KD) is determined by SPR or isothermal titration calorimetry (ITC) using purified NLRP3 protein and Selnolast concentrations ranging from 0.1 nM to 10 microM.
|
| Cell Assay |
Human THP‑1 monocytes are differentiated into macrophages with PMA (100 nM, 48 h). Cells are seeded in 96‑well plates, primed with LPS (200 ng/mL, 3 h), treated with Selnolast (0‑10 microM, 30 min), then activated with nigericin (10 microM, 1 h) or ATP (5 mM, 1 h). Supernatants are collected for human IL‑1beta ELISA. Cell viability is assessed by CCK‑8 or ATP‑luminescence to ensure that IL‑1beta reduction is not due to cytotoxicity. Caspase‑1 activity in cell lysates is measured using a fluorogenic substrate (Ac‑YVAD‑AFC).
|
| Animal Protocol |
Selnolast is formulated in a suitable vehicle (e.g., 0.5% methylcellulose or 10% DMSO/40% PEG300/5% Tween‑80/45% saline) and administered orally to mice (10‑30 mg/kg). For the DSS‑induced colitis model: female C57BL/6 mice receive 2.5% DSS in drinking water for 7 days to induce colitis. Selnolast is given daily by oral gavage starting on day 0. Disease activity index (body weight loss, stool consistency, fecal bleeding), colon length, and histological scores are evaluated. Colonic IL‑1beta, TNF‑alpha, and IL‑6 levels are measured by ELISA.
|
| ADME/Pharmacokinetics |
No PK data reported for Selnolast. For structurally related NLRP3 inhibitors, oral administration (10‑30 mg/kg) in mice typically achieves Cmax of 0.5‑5 microM within 0.5‑2 h (Tmax). Terminal half‑life (t1/2) ranges from 2‑6 h. Volume of distribution (Vd) is moderate (1‑3 L/kg), suggesting extravascular distribution. Plasma protein binding is usually high (>90%). Metabolic stability in liver microsomes (mouse, rat, human) is often assessed to predict clearance.
|
| Toxicity/Toxicokinetics |
No toxicity data specifically for Selnolast. For NLRP3 inhibitors in development, subchronic (28‑day) oral toxicity studies in rats (25‑150 mg/kg/day) evaluate target organs (liver, kidneys, bone marrow). Hematological parameters (white blood cell counts, platelet counts) are monitored for signs of myelosuppression. Histopathology may reveal thymic atrophy or lymphoid depletion due to anti‑inflammatory effects on immune tissues.
|
| References |
[1]. Cooper, Matthew, et al. Novel sulfonamidocarboxamide compounds as NLRP3 inhibitors and their preparation. Patent. WO2019008025.
|
| Additional Infomation |
Selnoflast is a small molecule drug. The International Nonproprietary Name (INN) stem "-noflast" in its name indicates that Selnoflast is an inhibitor of the NLRP3 inflammasome protein. Selnoflast is currently being investigated in the clinical trial NCT05924243 (a study RO7486967 investigating the safety, tolerability, pharmacokinetics, and pharmacodynamics of Selnoflast in patients with early-stage idiopathic Parkinson's disease). The monoisotopic molecular weight of Selnoflast is 391.19 Da.
Selnolast is an investigational NLRP3 inhibitor with no FDA or EMA approval to date. It has been evaluated in early‑phase clinical studies for systemic inflammatory conditions and possibly Alzheimer's disease. The compound was originally developed by Inflazome and later licensed to Roche. Further clinical development status remains uncertain as of current literature. |
| Molecular Formula |
C20H29N3O3S
|
|---|---|
| Molecular Weight |
391.5276
|
| Exact Mass |
391.192
|
| CAS # |
2260969-36-4
|
| Related CAS # |
Selnoflast calcium;2887416-19-3;Selnoflast potassium
|
| PubChem CID |
137402358
|
| Appearance |
White to off-white solid powder
|
| LogP |
3.7
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
27
|
| Complexity |
619
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
S(C1([H])C([H])([H])C([H])([H])N(C([H])([H])C([H])([H])[H])C([H])([H])C1([H])[H])(N([H])C(N([H])C1=C2C([H])([H])C([H])([H])C([H])([H])C2=C([H])C2C([H])([H])C([H])([H])C([H])([H])C=21)=O)(=O)=O
|
| InChi Key |
OHIFQOUPTWBQLE-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C20H29N3O3S/c1-2-23-11-9-16(10-12-23)27(25,26)22-20(24)21-19-17-7-3-5-14(17)13-15-6-4-8-18(15)19/h13,16H,2-12H2,1H3,(H2,21,22,24)
|
| Chemical Name |
1-(1-ethylpiperidin-4-yl)sulfonyl-3-(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)urea
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO: 5 mg/mL (12.77 mM)
1M NaOH: 3.33 mg/mL (8.51 mM; adjust pH to 12 with 1M NaOH) |
|---|---|
| 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 | 2.5541 mL | 12.7704 mL | 25.5408 mL | |
| 5 mM | 0.5108 mL | 2.5541 mL | 5.1082 mL | |
| 10 mM | 0.2554 mL | 1.2770 mL | 2.5541 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/NCT07448038
Conditions:AtherosclerosisLink: https://clinicaltrials.gov/ct2/show/NCT05924243
Conditions:Parkinson DiseaseProducts are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
