| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
CXCR2 IL-8
CXCR2 (CXC chemokine receptor 2) and the IL-8 receptor. Elubricin tosylate is a potent and selective CXCR2 antagonist that blocks the binding of chemokines such as IL-8 (CXCL8) and other CXCR2 ligands (e.g., GROalpha, ENA-78). By blocking CXCR2, it inhibits neutrophil activation, shape change, and chemotaxis to sites of inflammation. |
|---|---|
| ln Vitro |
On neutrophils, elubbrixin shows a dose-dependent inhibitory effect[1].
In vitro, elubricin tosylate (SB-656933 tosylate) is a specific, competitive, reversible CXCR2 antagonist. It inhibits ex vivo neutrophil CD11b upregulation with an IC50 of 260.7 nM, and neutrophil shape change with an IC50 of 310.5 nM. It also blocks CXCR2-mediated calcium flux and chemotaxis in human neutrophils. These effects are selective for CXCR2 with minimal activity against other chemokine receptors. |
| ln Vivo |
In vivo, elubricin tosylate demonstrates anti-inflammatory activity in animal models of airway inflammation. It reduces ozone-induced airway inflammation in humans, as measured by decreased sputum neutrophil counts and reduced levels of inflammatory markers. In rodent models of lung inflammation, it decreases neutrophil recruitment to the airways, reduces cytokine levels, and improves lung function parameters.
|
| Enzyme Assay |
A radioligand binding assay is used to determine CXCR2 affinity. Membranes from CXCR2-expressing cells are incubated with a radiolabeled CXCR2 ligand (e.g., 125I-IL-8) in the presence of serially diluted elubricin tosylate (0.1-1000 nM). Bound radioactivity is measured by filtration and scintillation counting, and the Ki is calculated. For functional antagonism, a calcium flux assay is performed using CXCR2-expressing cells loaded with a calcium-sensitive dye.
|
| Cell Assay |
For in vitro neutrophil activation assays, human peripheral blood neutrophils are isolated from healthy donors by density gradient centrifugation. Neutrophils are pre-incubated with serially diluted elubricin tosylate (1-1000 nM) for 10 minutes, then stimulated with CXCL8/IL-8 (10-100 ng/mL) or other CXCR2 agonists. CD11b upregulation is measured by flow cytometry using a CD11b antibody. Shape change is quantified by forward scatter changes using flow cytometry. Chemotaxis is measured in a transwell chamber. Cell viability is assessed using trypan blue exclusion.
|
| Animal Protocol |
In an ozone-induced airway inflammation model in healthy human volunteers, elubricin tosylate is administered orally at doses of 100-800 mg. Subjects undergo ozone exposure to induce airway inflammation. Sputum induction is performed before and after ozone exposure, and sputum neutrophils are counted. Plasma and sputum levels of CXCR2 ligands (IL-8, GROalpha) are measured by ELISA. Lung function (FEV1) is assessed by spirometry. In rodent models, elubricin tosylate (10-50 mg/kg, oral) is administered before intratracheal LPS or cigarette smoke exposure.
|
| ADME/Pharmacokinetics |
Elubricin tosylate has a molecular weight of 635.51 g/mol and a formula of C24H25Cl2FN4O7S2. It is orally bioactive with good absorption. In humans, the half-life is approximately 6-10 hours, supporting twice-daily dosing. Cmax is dose-proportional, and the volume of distribution is moderate. The tosylate salt improves aqueous solubility and stability. It is soluble in DMSO.
|
| Toxicity/Toxicokinetics |
Detailed toxicological data for elubricin tosylate are not fully published. In clinical studies, it was generally well-tolerated, with the most common adverse events including mild gastrointestinal disturbances (nausea, diarrhea) and headache. As a CXCR2 antagonist, it may cause mild neutropenia by blocking neutrophil trafficking from the bone marrow, though this is typically reversible and not associated with increased infection rates. No significant organ toxicity has been reported.
|
| References |
|
| Additional Infomation |
Elubricin tosylate (SB-656933 tosylate) has been investigated in clinical trials for inflammatory diseases, including COPD and asthma. It has not received regulatory approval for any indication. It is available for research purposes to study the role of CXCR2 and neutrophil-mediated inflammation in respiratory diseases, and to explore CXCR2 antagonism as a therapeutic strategy for chronic inflammatory disorders.
|
| Molecular Formula |
C24H25CL2FN4O7S2
|
|---|---|
| Molecular Weight |
635.51
|
| Exact Mass |
634.053
|
| CAS # |
960495-43-6
|
| Related CAS # |
Elubrixin hydrochloride;688763-65-7;Elubrixin;688763-64-6
|
| PubChem CID |
23634419
|
| Appearance |
White to off-white solid powder
|
| LogP |
6.832
|
| Hydrogen Bond Donor Count |
5
|
| Hydrogen Bond Acceptor Count |
10
|
| Rotatable Bond Count |
5
|
| Heavy Atom Count |
40
|
| Complexity |
883
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC1=CC=C(C=C1)S(=O)(=O)O.C1CN(CCN1)S(=O)(=O)C2=C(C=CC(=C2O)NC(=O)NC3=C(C(=CC=C3)F)Cl)Cl
|
| InChi Key |
CJAUWWGOABMMJX-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C17H17Cl2FN4O4S.C7H8O3S/c18-10-4-5-13(23-17(26)22-12-3-1-2-11(20)14(12)19)15(25)16(10)29(27,28)24-8-6-21-7-9-24;1-6-2-4-7(5-3-6)11(8,9)10/h1-5,21,25H,6-9H2,(H2,22,23,26);2-5H,1H3,(H,8,9,10)
|
| Chemical Name |
1-(2-chloro-3-fluorophenyl)-3-(4-chloro-2-hydroxy-3-piperazin-1-ylsulfonylphenyl)urea;4-methylbenzenesulfonic acid
|
| 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 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)
|
| Solubility (In Vitro) |
DMSO: 125 mg/mL (196.69 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.27 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (3.27 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (3.27 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5735 mL | 7.8677 mL | 15.7354 mL | |
| 5 mM | 0.3147 mL | 1.5735 mL | 3.1471 mL | |
| 10 mM | 0.1574 mL | 0.7868 mL | 1.5735 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/NCT00551811
Conditions:Pulmonary Disease, Chronic ObstructiveLink: https://clinicaltrials.gov/ct2/show/NCT00504439
Conditions:Pulmonary Disease, Chronic ObstructiveProducts are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
