Size | Price | Stock | Qty |
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5mg |
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10mg |
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25mg |
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50mg |
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100mg |
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250mg |
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Other Sizes |
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Purity: ≥98%
Danirixin (formerly known as GSK-1325756; GSK1325756) is a novel, potent small molecule CXCR2 antagonist being developed as a potential anti-inflammatory drug for COPD. It is a selective, high-affinity and reversible CXCR2 antagonist with IC50 of 12.5 nM for CXCL8. Danirixin, an oral CXCR2 antagonist, has been shown to inhibit agonist-induced neutrophil activation in a dose-dependent manner after single and repeated once-daily oral administration. This suggests that the drug may be useful in treating inflammatory diseases where neutrophils predominate. In many acute and chronic inflammatory diseases, there is an important role for excessive neutrophil activation and presence. One key player in regulating neutrophil extravasation and activation is the CXCR2 chemokine receptor. One possible strategy for decreasing neutrophil migration and activation is selective antagonistic action on the CXCR2 receptor.
Targets |
CXCL8-CXCR2 ( IC50 = 12.5 nM )
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ln Vitro |
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ln Vivo |
Danirixin inhibits CD11b upregulation in rat and human whole-blood experiments measuring neutrophil activation by surface CD11b expression after CXCL2 (rat) or CXCL1 (human) challenge, with pIC50s of 6.05 and 6.3, respectively. With median effective doses (ED50s) of 1.4 and 16 mg/kg, respectively, daririxin administered orally also prevents the influx of neutrophils into the lung in vivo in rats after an aerosol lipopolysaccharide or ozone challenge[1].
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Enzyme Assay |
It is a selective, high-affinity and reversible antagonist of CXCR2 with IC50 of 12.5 nM for CXCL8.
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Animal Protocol |
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References |
Molecular Formula |
C19H21CLFN3O4S
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Molecular Weight |
441.90
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Exact Mass |
441.09
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Elemental Analysis |
C, 51.64; H, 4.79; Cl, 8.02; F, 4.30; N, 9.51; O, 14.48; S, 7.25
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CAS # |
954126-98-8
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Related CAS # |
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Appearance |
Solid powder
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SMILES |
CC1=C(C=CC=C1F)NC(=O)NC2=C(C(=C(C=C2)Cl)S(=O)(=O)[C@H]3CCCNC3)O
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InChi Key |
NGYNBSHYFOFVLS-LBPRGKRZSA-N
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InChi Code |
InChI=1S/C19H21ClFN3O4S/c1-11-14(21)5-2-6-15(11)23-19(26)24-16-8-7-13(20)18(17(16)25)29(27,28)12-4-3-9-22-10-12/h2,5-8,12,22,25H,3-4,9-10H2,1H3,(H2,23,24,26)/t12-/m0/s1
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Chemical Name |
1-[4-chloro-2-hydroxy-3-[(3S)-piperidin-3-yl]sulfonylphenyl]-3-(3-fluoro-2-methylphenyl)urea
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Synonyms |
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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 |
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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) |
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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 | 2.2630 mL | 11.3148 mL | 22.6296 mL | |
5 mM | 0.4526 mL | 2.2630 mL | 4.5259 mL | |
10 mM | 0.2263 mL | 1.1315 mL | 2.2630 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.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT02469298 | Completed | Drug: GSK1325756 (Danirixin) Drug: Oseltamivir Phosphate |
Virus Diseases | GlaxoSmithKline | June 1, 2015 | Phase 2 |
NCT03034967 | Completed | Drug: Danirixin Drug: Standard of care |
Pulmonary Disease, Chronic Obstructive |
GlaxoSmithKline | April 25, 2017 | Phase 2 |
NCT03457727 | Completed | Drug: Danirixin Drug: Omeprazole |
Pulmonary Disease, Chronic Obstructive |
GlaxoSmithKline | March 7, 2018 | Phase 1 |
NCT02453022 | Completed | Drug: Danirixin HBr 50 mg IR Tablet Drug: Danirixin FB 50 mg IR Tablet |
Pulmonary Disease, Chronic Obstructive |
GlaxoSmithKline | May 18, 2015 | Phase 1 |
NCT02130193 | Completed | Drug: Danirixin Drug: Placebo |
Pulmonary Disease, Chronic Obstructive |
GlaxoSmithKline | February 13, 2014 | Phase 2 |
Plot of inhibition of ex vivo CXCL1-induced CD11b expression versus whole blood concentration of danirixin for Study 1.BMC Pharmacol Toxicol.2015 Jun 20;16:18. th> |
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Mean pharmacokinetics concentration plot versus time for Study 2 (Fed versus Fasted, Elderly, Omeprazole Interaction).BMC Pharmacol Toxicol.2015 Jun 20;16:18. td> |
Adjusted geometric means of ratio to baseline ex vivo CXCL-induced CD11b expression (0–24 h) versus time for single dose Study 1 (FTIH): fractional increase from control (CXCL1 0 nM) with 95% CIs.BMC Pharmacol Toxicol.2015 Jun 20;16:18. td> |