| 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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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 )
C-X-C chemokine receptor type 2 (CXCR2) (Ki = 0.4 nM for human CXCR2; IC₅₀ = 0.8 nM for inhibiting CXCL8 binding to human CXCR2; IC₅₀ = 1.2 nM for inhibiting CXCR2-mediated calcium mobilization); C-X-C chemokine receptor type 1 (CXCR1) (Ki = 35 nM for human CXCR1; IC₅₀ = 42 nM for inhibiting CXCL8 binding to human CXCR1); >1000-fold selectivity over CXCR3, CXCR4, CCR1, CCR2, CCR5, CCR7, 5-HT receptors, adrenergic receptors (Ki > 1000 nM for all) [1][3] |
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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].
Mouse LPS-induced acute lung injury (ALI) model: Intraperitoneal administration of Danirixin (1, 3, 10 mg/kg) 1 hour before LPS challenge dose-dependently reduced lung inflammation. It decreased BALF neutrophil counts (by 45%, 68%, 82%), MPO activity (by 40%, 65%, 78%), and lung tissue levels of IL-6, TNF-α, and CXCL1 (by 50–75% at 10 mg/kg). Histological analysis showed reduced alveolar edema and inflammatory cell infiltration [1] - Diet-induced obese (DIO) mouse model: Oral administration of Danirixin (10, 30 mg/kg, once daily for 12 weeks) improved glucose tolerance (AUC reduced by 30% and 45%), increased insulin sensitivity (HOMA-IR reduced by 35% and 50%), and reduced visceral adipose tissue (VAT) mass (by 20% and 32%). It also decreased VAT inflammation, as evidenced by 40–55% lower infiltration of CD11b+F4/80+ macrophages and reduced levels of IL-6, TNF-α in VAT [4] - Rat carrageenan-induced paw edema model: Oral administration of Danirixin (3, 10, 30 mg/kg) 1 hour before carrageenan injection dose-dependently reduced paw edema (by 35%, 55%, 70%) and hyperalgesia (mechanical withdrawal threshold increased by 40%, 60%, 75% at 4 hours post-injection) [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.
CXCR2/CXCR1 radioligand binding assay: Membranes from human CXCR2- or CXCR1-expressing HEK293 cells were suspended in binding buffer (Tris-HCl, MgCl₂, 0.1% BSA). Danirixin was serially diluted (0.001–1000 nM) and mixed with membranes and tritiated CXCL8. The mixture was incubated at 25°C for 120 minutes, then filtered through pre-wetted glass fiber filters to separate bound and free ligands. Radioactivity was measured by liquid scintillation counting, and Ki/IC₅₀ values were calculated via nonlinear regression analysis of displacement curves [1][3] - Calcium mobilization assay: CXCR2-expressing CHO cells were loaded with a calcium-sensitive fluorescent dye (Fura-2 AM) for 45 minutes at 37°C. Danirixin (0.001–100 nM) was preincubated with cells for 20 minutes, followed by stimulation with CXCL8 (10 nM). Fluorescence intensity (excitation 340/380 nm, emission 510 nm) was measured in real-time using a microplate reader, and IC₅₀ values were derived from dose-response curves [1] - Receptor selectivity assay: Membranes from cells expressing other chemokine receptors (CXCR3, CXCR4, CCR1, etc.) or GPCRs (5-HT receptors, adrenergic receptors) were prepared as described. Danirixin was tested at concentrations up to 10 μM, and binding affinity (Ki) was determined to assess selectivity [3] |
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| Cell Assay |
Human neutrophil chemotaxis assay: Neutrophils were isolated from human peripheral blood by density gradient centrifugation and resuspended in RPMI 1640 medium. Danirixin (0.01–100 nM) was mixed with neutrophils, which were added to the upper chamber of a transwell insert (5 μm pore size). CXCL8, CXCL1, or CXCL5 (10 nM each) was added to the lower chamber, and the plate was incubated at 37°C with 5% CO₂ for 2 hours. Migrated neutrophils were counted using a hemocytometer, and inhibition rates were calculated relative to vehicle controls [1]
- Human adipocyte inflammation assay: Human visceral adipocytes were seeded in 6-well plates (2×10⁵ cells/well) and differentiated for 14 days. Cells were pretreated with Danirixin (1, 5, 10 μM) for 1 hour, then stimulated with LPS (1 μg/mL) for 24 hours. Total RNA was extracted to measure cytokine/chemokine mRNA levels by qPCR, and culture supernatants were collected to detect protein levels by ELISA. For signaling analysis, cells were lysed in RIPA buffer with inhibitors, and proteins were analyzed by western blot using antibodies against phospho-NF-κB p65, phospho-ERK1/2, total NF-κB p65, total ERK1/2, and GAPDH [5] - Neutrophil activation assay: Human neutrophils were pretreated with Danirixin (10 nM) for 15 minutes, then activated with TNF-α (10 ng/mL) for 30 minutes. Expression of CD11b (activation marker) was measured by flow cytometry, and superoxide anion production was detected by chemiluminescence [1] |
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| Animal Protocol |
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| ADME/Pharmacokinetics |
In rats: After oral administration (10 mg/kg), the peak plasma concentration (Cₘₐₓ) was 2.1 μg/mL, the time to peak concentration (Tₘₐₓ) was 1.0 h, the terminal half-life (t₁/₂) was 7.5 h, the volume of distribution (Vd) was 2.8 L/kg, and the oral bioavailability was 68%. The clearance (CL) after intravenous administration (5 mg/kg) was 0.31 L/h/kg [3] In dogs: After oral administration (10 mg/kg), the peak plasma concentration (Cₘₐₓ) was 2.7 μg/mL, the time to peak concentration (Tₘₐₓ) was 1.5 h, the half-life (t₁/₂) was 9.2 h, the volume of distribution (Vd) was 2.5 L/kg, and the oral bioavailability was 75%. Intravenous injection (5 mg/kg) showed a CL of 0.25 L/h/kg [3]
- Tissue distribution: In rats, 2 hours after oral administration (10 mg/kg), dannisin was distributed in the lungs (tissue/plasma ratio = 3.2), liver (2.9), spleen (2.5), kidneys (2.3) and visceral adipose tissue (1.9); the concentration in brain tissue was lower (tissue/plasma ratio = 0.2) [3] - Excretion: 72 hours after intravenous injection (5 mg/kg) in rats, 70% of the dose was excreted in the urine (35% as the original drug and 35% as metabolites), and 20% was excreted in the feces (8% as the original drug and 12% as metabolites) [3] - Metabolism: In humans, the main metabolic pathways include oxidation and glucuronidation, and no toxic metabolites were detected in liver microsomal studies [3] |
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| Toxicity/Toxicokinetics |
Plasma protein binding: As determined by ultrafiltration, the plasma protein binding of Daniloxine was 95% in human plasma, 93% in rat plasma, and 94% in canine plasma [3]. Acute toxicity: In rats and dogs, the oral LD₅₀ was >300 mg/kg. In a 7-day acute study, no significant toxicity (convulsions, respiratory depression, weight loss, death) was observed at doses up to 150 mg/kg [2]. Subchronic toxicity: In a 28-day repeated oral administration study in rats (10, 30, 100 mg/kg/day), the compound did not cause significant changes in body weight, food intake, hematological parameters (erythrocytes, leukocytes, platelets) or liver and kidney function (ALT, AST, creatinine, BUN). No histopathological abnormalities were found in major organs (liver, kidney, heart, lung, spleen) [2]
- Drug interactions: In vitro studies have shown that no inhibitory effect on cytochrome P450 enzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, CYP3A4) was observed at concentrations up to 10 μM [3] - No genotoxicity: At concentrations up to 100 μM, Daniroxine did not induce Ames test mutations or human lymphocyte chromosomal aberrations [2] |
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| References | |||
| Additional Infomation |
Danirixin has been used in clinical trials for the treatment of viral diseases, nutritional status, lung diseases, chronic obstructive pulmonary disease and infections, respiratory syncytial virus, and basic scientific research. Danirixin is a potent, highly selective, orally bioavailable CXCR2 antagonist with weak cross-reactivity to CXCR1 and has been developed for the treatment of inflammatory and metabolic diseases [1][3]. Its core mechanism of action includes selectively competitively blocking CXCR2, inhibiting the binding of pro-inflammatory chemokines (CXCL1, CXCL5, CXCL8) and subsequent neutrophil recruitment/activation, and inhibiting pro-inflammatory signaling pathways (NF-κB, ERK1/2) in target tissues (lung, adipose tissue) [1][5]. Preclinical data support its potential therapeutic use in acute lung injury, obesity-related metabolic disorders (insulin resistance, type 2 diabetes), etc. Relieves inflammatory pain by reducing tissue inflammation and improving metabolic homeostasis [1][4] - This compound has good drug-like properties: high oral bioavailability (68-75% in preclinical animal models), long half-life (7.5-9.2 hours), target tissue distribution (lung, adipose tissue), low toxicity, and no significant risk of drug interaction [3] - The high selectivity of Danirixin for CXCR2 minimizes off-target effects on CXCR1 or other GPCRs, thereby reducing the risk of unintended immunomodulation [1][3]
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| Molecular Formula |
C19H21CLFN3O4S
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| Molecular Weight |
441.90
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| Exact Mass |
441.092
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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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| PubChem CID |
24780598
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| Appearance |
White to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Boiling Point |
533.1±50.0 °C at 760 mmHg
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| Flash Point |
276.2±30.1 °C
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| Vapour Pressure |
0.0±1.5 mmHg at 25°C
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| Index of Refraction |
1.638
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| LogP |
3.93
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
29
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| Complexity |
677
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| Defined Atom Stereocenter Count |
1
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| SMILES |
S([C@@H]1CNCCC1)(C1C(Cl)=CC=C(NC(=O)NC2C=CC=C(F)C=2C)C=1O)(=O)=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. |
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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. |
 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. |
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