Danirixin

Alias: Danirixin; GSK-1325756; GSK1325756; GSK 1325756

Cat No.:V3796 Purity: ≥98%

COA Product Data Instructions for use SDS

Danirixin (formerly known asGSK-1325756; GSK1325756) is a novel, potent small molecule CXCR2 antagonist being developed as a potential anti-inflammatory drug for COPD.

Danirixin Chemical Structure CAS No.: 954126-98-8
Product category: CXCR

This product is for research use only, not for human use. We do not sell to patients.

Size	Price	Stock	Qty
5mg
10mg
25mg
50mg
100mg
250mg
Other Sizes

ADD TO CART CHECKOUT BULK INQUIRY

1-708-310-1919 sales@invivochem.com

Official Supplier of:

Business Relationship with 5000+ Clients Globally
Major Universities, Research Institutions, Biotech & Pharma
Citations by Top Journals: Nature, Cell, Science, etc.

Top Publications Citing lnvivochem Products

Nature 2021, 597(7874):119-125.

Cell 2020,183:1202-1218.e25.

Science Adv 2022: 8, eabm9427.

Nature 597, 119–125 (2021)

Cell Stem Cell 2020,26(6):845-861.e12.

Science Trans Med 2023,15(701):eadd7872.

STTT 2023,8(1):91.

Cell Reports 2023,42(4):112313

Science Trans Med 2023, 15: eadd7872.

Cancer Cell 2021,39(4):529-547.e7.

Cancer Discov 2022,12(4):1106-1127.

Immunity 2023,56(3):620-634.e11.

J Am Chem Soc 2022,144:21831-21836.

Cell 2020,183:1202-1218.e25.

Science Adv 2022:8,eabm9427.

Nature 2021,597(7874):119-125.

Cell 2020,183:1202-1218.e25.

PNAS Nexus 2022,1(3):pgac063.

ACS Nano 2023,17(10):9110-9125.

Biomaterial 2023 Sep16:302:122333.

Purity & Quality Control Documentation

Current batch：

Purity: ≥98%

COA

MSDS

Instructions

Product Description
Bioactivity & Protocols
Physicochemical Properties
Solubility Data
Calculators
Clinical Trial Information
Biological Data

Product Description

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.

Biological Activity I Assay Protocols (From Reference)

Targets

CXCL8-CXCR2 ( IC50 = 12.5 nM )

ln Vitro

In vitro activity: Danirixin has a great affinity for CXCR2, binding to human CXCR2 expressed in Chinese hamster ovary cells (CHO) with a negative log of the 50% inhibitory concentration (pIC50) of 7.9 and 78-fold selectivity over binding to CXCR1 expressed in CHO. With a KB of 6.5 nM and antagonist potency (pA2) of 8.44, danirixin is a competitive antagonist against CXCL8 in Ca2+-mobilization assays. It is also fully reversible in washout experiments over a 180-minute duration[1].

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].

Enzyme Assay

It is a selective, high-affinity and reversible antagonist of CXCR2 with IC50 of 12.5 nM for CXCL8.

Animal Protocol

10 mg, 25 mg, 50 mg, 100 mg, and 200 mg

There were no serious adverse events and no adverse events considered to be of clinical relevance. There were no withdrawals due to adverse events. Systemic exposure following single doses of danirixin 10 mg, 25 mg, 50 mg, 100 mg, and 200 mg increased with increasing dose. Engagement of pharmacology was demonstrated as inhibition of ex-vivo CXCL1-induced CD11b expression on peripheral blood neutrophils when compared to placebo (approximately 50% for 50 mg and 100 mg danirixin, and 72% at 200 mg). There was a 37% decrease in Cmax and a 16% decrease in AUC (0-∞) following administration of danirixin in the presence of food. Cmax also decreased by 65% when danirixin 100 mg was administered following omeprazole 40 mg once daily for 5 days. The AUC (0-∞) and Cmax were 50% lower in elderly subjects compared with younger subjects.

References

[1]. J Pharmacol Exp Ther . 2017 Aug;362(2):338-346.

[2]. BMC Pharmacol Toxicol. 2015, 16: 18.

[3]. Drug Metab Dispos . 2010 Mar;38(3):405-14.

[4]. Diabetes Obes Metab . 2010 Nov;12(11):1004-12.

[5]. Nutrients . 2021 Nov 15;13(11):4088.

These protocols are for reference only. InvivoChem does not independently validate these methods.

Physicochemical Properties

Molecular Formula

C19H21CLFN3O4S

Molecular Weight

441.90

Exact Mass

441.09

Elemental Analysis

C, 51.64; H, 4.79; Cl, 8.02; F, 4.30; N, 9.51; O, 14.48; S, 7.25

CAS #

954126-98-8

Related CAS #

954126-98-8

Appearance

Solid powder

SMILES

CC1=C(C=CC=C1F)NC(=O)NC2=C(C(=C(C=C2)Cl)S(=O)(=O)[C@H]3CCCNC3)O

InChi Key

NGYNBSHYFOFVLS-LBPRGKRZSA-N

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

Chemical Name

1-[4-chloro-2-hydroxy-3-[(3S)-piperidin-3-yl]sulfonylphenyl]-3-(3-fluoro-2-methylphenyl)urea

Synonyms

Danirixin; GSK-1325756; GSK1325756; GSK 1325756

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 Data

Solubility (In Vitro)

DMSO: ~8 mg/mL (~18.1 mM)

Water: <1mg/mL

Ethanol: <1mg/mL

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
(e.g. IP/IV/IM/SC)

Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)
*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)]
*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.
Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline)
Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline)
Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline)
Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline
Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil)
Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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
Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose
Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose
Oral Formulation 6: Mixing with food powders

Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.

(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.

Calculator

Mass

Concentration

Volume

Molecular Weight*

Calculate Reset

Molarity Calculator allows you to calculate the mass, volume, and/or concentration required for a solution, as detailed below:

Calculate the Mass of a compound required to prepare a solution of known volume and concentration
Calculate the Volume of solution required to dissolve a compound of known mass to a desired concentration
Calculate the Concentration of a solution resulting from a known mass of compound in a specific volume

See Example

An example of molarity calculation using the molarity calculator is shown below:
What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?

Enter 350.26 in the Molecular Weight (MW) box
Enter 10 in the Concentration box and choose the correct unit (mM)
Enter 5 in the Volume box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 17.513 mg appears in the Mass box. In a similar way, you may calculate the volume and concentration.

Concentration (Start)

Volume (Start)

Concentration (End)

Volume (End)

Calculate Reset

Dilution Calculator allows you to calculate how to dilute a stock solution of known concentrations. For example, you may Enter C1, C2 & V2 to calculate V1, as detailed below:

What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:

Enter 10 into the Concentration (Start) box and choose the correct unit (mM)
Enter 25 into the Concentration (End) box and select the correct unit (mM)
Enter 25 into the Volume (End) box and choose the correct unit (mL)
Click the “Calculate” button
The answer of 62.5 μL (0.1 ml) appears in the Volume (Start) box

Molecular formula

Total molecular weight

g/mol

Calculate Reset

Molecular Weight Calculator allows you to calculate the molar mass and elemental composition of a compound, as detailed below:

Note: Chemical formula is case sensitive: C12H18N3O4 c12h18n3o4
Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter the chemical/molecular formula and click the “Calculate’ button.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (or molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Volume (to add to vial)

Mass (in vial)

Desired Reconstitution Concentration

Calculate Reset

Reconstitution Calculator allows you to calculate the volume of solvent required to reconstitute your vial.

Enter the mass of the reagent and the desired reconstitution concentration as well as the correct units
Click the “Calculate” button
The answer appears in the Volume (to add to vial) box

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)

Dosage mg/kg

Average weight of animals g

Dosing volume per animal μL

Number of animals

Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)

% DMSO

% Tween 80

% ddH₂O

Calculate Reset

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.

Note： (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.

Clinical Trial Information

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

Biological Data

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.
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.