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MedKoo Cat#: 319712 | Name: Danirixin
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Description:

WARNING: This product is for research use only, not for human or veterinary use.

Danirixin, also known as GSK1325756, is a potent, high-affinity, selective and reversible CXCR2 antagonist in development for treatment of chronic obstructive pulmonary disease. The dose-dependent inhibition of agonist-induced neutrophil activation following single and repeated once daily oral administration of danirixin suggests that this CXCR2 antagonist may have benefit in neutrophil-predominant inflammatory diseases.

Chemical Structure

Danirixin
Danirixin
CAS#954126-98-8

Theoretical Analysis

MedKoo Cat#: 319712

Name: Danirixin

CAS#: 954126-98-8

Chemical Formula: C19H21ClFN3O4S

Exact Mass: 441.0925

Molecular Weight: 441.90

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

Price and Availability

Size Price Availability Quantity
5mg USD 90.00 Ready to ship
10mg USD 150.00 Ready to ship
25mg USD 250.00 Ready to ship
50mg USD 450.00 Ready to ship
100mg USD 750.00 Ready to ship
200mg USD 1,250.00 Ready to ship
500mg USD 2,650.00 Ready to Ship
1g USD 4,250.00 Ready to Ship
2g USD 6,450.00 Ready to Ship
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Related CAS #
No Data
Synonym
GSK1325756; GSK-1325756; GSK 1325756; Danirixin;
IUPAC/Chemical Name
(S)-1-(4-chloro-2-hydroxy-3-(piperidin-3-ylsulfonyl)phenyl)-3-(3-fluoro-2-methylphenyl)urea
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
SMILES Code
ClC(C(S([C@H]1CCCNC1)(=O)=O)=C2O)=CC=C2NC(NC3=CC=CC(F)=C3C)=O
Appearance
Solid powder
Purity
>98% (or refer to the Certificate of Analysis)
Shipping Condition
Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition
Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility
DMSO 5mg/mL with warm and sonication
Shelf Life
>2 years if stored properly
Drug Formulation
This drug may be formulated in DMSO
Stock Solution Storage
0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code
2934.99.9001
More Info
Biological target:
Danirixin is a selective, and reversible CXCR2 antagonist, with IC50 of 12.5 nM for CXCL8.
In vitro activity:
Using CT26 tumor tissues, the DC activation genes were analyzed by qRT-PCR, and the results supported the relationship between CXCL8 and DCs activation marker in TCGA cohort. As expected, expression of DCs activation genes such as CD54, CD83 and CD86 were declined significantly in the group treated with danirixin in comparison to the untreated group (Figure 6A). To further validate the finding on danirixin inhibit DCs infiltration, transwell migration assays were carried out. Flow cytometric analyses showed a significant decrease of DCs among total splenocytes migrating toward CT26 cell culture supernatant fluids after treated with danirixin (Figure 6C). Reference: Front Immunol. 2021; 12: 667177. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138166/
In vivo activity:
To test the differential contributions of immune and tumor components to progression, three CRC cell lines, CT26, MC38 and HCT116, were used. In vivo treatment with danirixin (antagonists of CXCR2) promoted tumor progression in animal models established with CT26 cells. Danirixin was found to promote tumor growth in CT26 model, but not reparixin treated mouse in either CT26 or MC38 model (Figure 5A). CXCR2 antagonism may function via an immune component, with CXCR2 antagonist treatment in mice resulting in reduced activated DCs and correlating with decreased Interferon gamma (IFN-γ) or Granzyme B expressed CD8+ T cells. Reference: Front Immunol. 2021; 12: 667177. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8138166/
Solvent mg/mL mM
Solubility
DMSO 5.0 0.00
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 441.90 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol:
1. Li E, Yang X, Du Y, Wang G, Chan DW, Wu D, Xu P, Ni P, Xu D, Hu Y. CXCL8 Associated Dendritic Cell Activation Marker Expression and Recruitment as Indicators of Favorable Outcomes in Colorectal Cancer. Front Immunol. 2021 May 7;12:667177. doi: 10.3389/fimmu.2021.667177. PMID: 34025668; PMCID: PMC8138166.
In vitro protocol:
1. Li E, Yang X, Du Y, Wang G, Chan DW, Wu D, Xu P, Ni P, Xu D, Hu Y. CXCL8 Associated Dendritic Cell Activation Marker Expression and Recruitment as Indicators of Favorable Outcomes in Colorectal Cancer. Front Immunol. 2021 May 7;12:667177. doi: 10.3389/fimmu.2021.667177. PMID: 34025668; PMCID: PMC8138166.
In vivo protocol:
1. Li E, Yang X, Du Y, Wang G, Chan DW, Wu D, Xu P, Ni P, Xu D, Hu Y. CXCL8 Associated Dendritic Cell Activation Marker Expression and Recruitment as Indicators of Favorable Outcomes in Colorectal Cancer. Front Immunol. 2021 May 7;12:667177. doi: 10.3389/fimmu.2021.667177. PMID: 34025668; PMCID: PMC8138166.
1: Su S, Hou C, Tang Q. Inhibition of chemokine receptor CXCR2 attenuates postoperative peritoneal adhesion formation. Surgery. 2024 Apr;175(4):1081-1088. doi: 10.1016/j.surg.2023.12.018. Epub 2024 Jan 27. PMID: 38281854. 2: Falter J, Lohmeier A, Eberl P, Stoerr EM, Koskimäki J, Falter L, Rossmann J, Mederer T, Schmidt NO, Proescholdt M. CXCR2-Blocking Has Context-Sensitive Effects on Rat Glioblastoma Cell Line Outgrowth (S635) in an Organotypic Rat Brain Slice Culture Depending on Microglia-Depletion (PLX5622) and Dexamethasone Treatment. Int J Mol Sci. 2023 Nov 27;24(23):16803. doi: 10.3390/ijms242316803. PMID: 38069130; PMCID: PMC10706712. 3: Zhou M, Ma Y, Chiang CC, Rock EC, Luker KE, Luker GD, Chen YC. High- Throughput Cellular Heterogeneity Analysis in Cell Migration at the Single-Cell Level. Small. 2023 Feb;19(6):e2206754. doi: 10.1002/smll.202206754. Epub 2022 Nov 30. PMID: 36449634; PMCID: PMC9908848. 4: Oh KK, Adnan M, Cho DH. New Insight into Drugs to Alleviate Atopic March via Network Pharmacology-Based Analysis. Curr Issues Mol Biol. 2022 May 18;44(5):2257-2274. doi: 10.3390/cimb44050153. PMID: 35678682; PMCID: PMC9164039. 5: Mohan D, Keir HR, Richardson H, Mayhew D, Boyer J, van der Schee MP, Allsworth MD, Miller BE, Tal-Singer R, Chalmers JD. Exhaled volatile organic compounds and lung microbiome in COPD: a pilot randomised controlled trial. ERJ Open Res. 2021 Oct 4;7(4):00253-2021. doi: 10.1183/23120541.00253-2021. PMID: 34616836; PMCID: PMC8488227. 6: Llanos-Paez C, Ambery C, Yang S, Tabberer M, Beerahee M, Plan EL, Karlsson MO. Improved Decision-Making Confidence Using Item-Based Pharmacometric Model: Illustration with a Phase II Placebo-Controlled Trial. AAPS J. 2021 Jun 2;23(4):79. doi: 10.1208/s12248-021-00600-1. PMID: 34080077; PMCID: PMC8172506. 7: Li E, Yang X, Du Y, Wang G, Chan DW, Wu D, Xu P, Ni P, Xu D, Hu Y. CXCL8 Associated Dendritic Cell Activation Marker Expression and Recruitment as Indicators of Favorable Outcomes in Colorectal Cancer. Front Immunol. 2021 May 7;12:667177. doi: 10.3389/fimmu.2021.667177. PMID: 34025668; PMCID: PMC8138166. 8: Nie G, Cao X, Mao Y, Lv Z, Lv M, Wang Y, Wang H, Liu C. Tumor-associated macrophages-mediated CXCL8 infiltration enhances breast cancer metastasis: Suppression by Danirixin. Int Immunopharmacol. 2021 Jun;95:107153. doi: 10.1016/j.intimp.2020.107153. Epub 2021 Mar 5. PMID: 33677254. 9: Keir HR, Richardson H, Fillmore C, Shoemark A, Lazaar AL, Miller BE, Tal- Singer R, Chalmers JD, Mohan D. CXCL-8-dependent and -independent neutrophil activation in COPD: experiences from a pilot study of the CXCR2 antagonist danirixin. ERJ Open Res. 2020 Nov 10;6(4):00583-2020. doi: 10.1183/23120541.00583-2020. PMID: 33263062; PMCID: PMC7682717. 10: Lloyd RS, Hingle MI, Bloomer JC, Charles SJ, Butler JM, Paul A, Zhu X, Miller B, D'Amico D, Donald A, Tal-Singer R, Ambery C. Negative Food Effect of Danirixin: Use of PBPK Modelling to Explore the Effect of Formulation and Meal Type on Clinical PK. Pharm Res. 2020 Oct 29;37(12):233. doi: 10.1007/s11095-020-02948-z. PMID: 33123802. 11: Lazaar AL, Miller BE, Donald AC, Keeley T, Ambery C, Russell J, Watz H, Tal- Singer R; for 205724 Investigators. CXCR2 antagonist for patients with chronic obstructive pulmonary disease with chronic mucus hypersecretion: a phase 2b trial. Respir Res. 2020 Jun 12;21(1):149. doi: 10.1186/s12931-020-01401-4. PMID: 32532258; PMCID: PMC7291447. 12: Iida T, Matsuzawa Y, Ogura H, Nagakubo T, Wakamatsu A, Ambery C, Miller BE, Lazaar AL, Numachi Y. Evaluation of the Safety, Tolerability, Pharmacokinetics, and Food Effect of Danirixin Hydrobromide Tablets in Japanese Healthy Elderly Participants. Clin Pharmacol Drug Dev. 2019 Nov;8(8):1081-1087. doi: 10.1002/cpdd.693. Epub 2019 May 6. PMID: 31056840. 13: Madan A, Chen S, Yates P, Washburn ML, Roberts G, Peat AJ, Tao Y, Parry MF, Barnum O, McClain MT, Roy-Ghanta S. Efficacy and Safety of Danirixin (GSK1325756) Co-administered With Standard-of-Care Antiviral (Oseltamivir): A Phase 2b, Global, Randomized Study of Adults Hospitalized With Influenza. Open Forum Infect Dis. 2019 Apr 3;6(4):ofz163. doi: 10.1093/ofid/ofz163. PMID: 31041358; PMCID: PMC6483311. 14: Roberts G, Chen S, Yates P, Madan A, Walker J, Washburn ML, Peat AJ, Soucie G, Kerwin E, Roy-Ghanta S. Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Tolerability, and Clinical Effect of Danirixin in Adults With Acute, Uncomplicated Influenza. Open Forum Infect Dis. 2019 Apr 22;6(4):ofz072. doi: 10.1093/ofid/ofz072. PMID: 31024969; PMCID: PMC6476494. 15: Uddin M, Watz H, Malmgren A, Pedersen F. NETopathic Inflammation in Chronic Obstructive Pulmonary Disease and Severe Asthma. Front Immunol. 2019 Feb 5;10:47. doi: 10.3389/fimmu.2019.00047. PMID: 30804927; PMCID: PMC6370641. 16: Lazaar AL, Miller BE, Tabberer M, Yonchuk J, Leidy N, Ambery C, Bloomer J, Watz H, Tal-Singer R. Effect of the CXCR2 antagonist danirixin on symptoms and health status in COPD. Eur Respir J. 2018 Oct 4;52(4):1801020. doi: 10.1183/13993003.01020-2018. PMID: 30139779. 17: Busch-Petersen J, Carpenter DC, Burman M, Foley J, Hunsberger GE, Kilian DJ, Salmon M, Mayer RJ, Yonchuk JG, Tal-Singer R. Danirixin: A Reversible and Selective Antagonist of the CXC Chemokine Receptor 2. J Pharmacol Exp Ther. 2017 Aug;362(2):338-346. doi: 10.1124/jpet.117.240705. Epub 2017 Jun 13. PMID: 28611093. 18: Bloomer JC, Ambery C, Miller BE, Connolly P, Garden H, Henley N, Hodnett N, Keel S, Kreindler JL, Lloyd RS, Matthews W, Yonchuk J, Lazaar AL. Identification and characterisation of a salt form of Danirixin with reduced pharmacokinetic variability in patient populations. Eur J Pharm Biopharm. 2017 Aug;117:224-231. doi: 10.1016/j.ejpb.2017.03.023. Epub 2017 Apr 3. PMID: 28385615. 19: Gross N. The COPD Pipeline, XXVIII. Chronic Obstr Pulm Dis. 2015 Jul 14;2(3):259-263. doi: 10.15326/jcopdf.2.3.2015.0149. PMID: 28848847; PMCID: PMC5556888. 20: Miller BE, Mistry S, Smart K, Connolly P, Carpenter DC, Cooray H, Bloomer JC, Tal-Singer R, Lazaar AL. The pharmacokinetics and pharmacodynamics of danirixin (GSK1325756)--a selective CXCR2 antagonist --in healthy adult subjects. BMC Pharmacol Toxicol. 2015 Jun 20;16:18. doi: 10.1186/s40360-015-0017-x. PMID: 26092545; PMCID: PMC4475328.