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Purity: ≥98%
Navarixin (formerly known as MK-7123; SCH527123; PS291822) is a novel potent and specific allosteric antagonist of CXCR1 and CXCR2 with antitumor and anti-inflammatory activity and is able to sensitize cells to oxaliplatin in preclinical colon cancer models. Its Kd values are 41 nM for cynomolgus CXCR1 and 0.20 nM, 0.20 nM, and 0.08 nM for cynomolgus monkey CXCR2, mouse, and rat, respectively. Navarixin exhibited reversible and saturable binding to CXCR1 and CXCR2. Navarixin exhibited good affinity towards CXCR1 (K(d) = 3.9 +/- 0.3 nM); however, it is selective towards CXCR2 (K(d) = 0.049 +/- 0.004 nM). All of the information combined indicates that Navarixin is a new, strong, and targeted CXCR2 antagonist that may be used therapeutically to treat a range of inflammatory diseases.
| Targets |
125I-CXCL8-CXCR2 ( IC50 = 0.97 nM ); Cynomolgus CXCR2 ( Kd = 0.08 nM ); Mouse CXCR2 ( Kd = 0.2 nM ); Rat CXCR2 ( Kd = 0.2 nM ); 125I-CXCL8-CXCR1 ( IC50 = 43 nM ); Cynomolgus CXCR1 ( Kd = 41 nM )
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| Enzyme Assay |
Navarixin, formerly known as MK-7123, SCH527123, or PS291822, is a novel, potent, and specific allosteric antagonist of CXCR1 and CXCR2 that exhibits antitumor activity. In preclinical models of colon cancer, it has the ability to sensitize cells to oxaliplatin. Its Kd values are 41 nM for cynomolgus CXCR1 and 0.20 nM, 0.20 nM, and 0.08 nM for cynomolgus monkey CXCR2, mouse, and rat, respectively. Navarixin exhibited reversible and saturable binding to CXCR1 and CXCR2.
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| Cell Assay |
The assay buffer (phenol red free-RPMI 1640 supplemented with 2% FBS) is used to resuspend recombinant cells at a density of 1×106/mL. The same assay buffer containing 5% FBS is used to resuscend human neutrophils at a density of 2 × 106/mL. High affinity is only exhibited by CXCL1 by CXCR2; however, CXCL8 exhibits high affinity for both CXCR1 and CXCR2. Filter is placed over the bottom wells of disposable microchemotaxis plates after 30 μL of chemoattractants diluted in assay buffer are poured into them. Navarixin (1–300 nM) is preincubated for 90 minutes in a CO2 incubator with cells. On each spot on the filter, cell aliquots (25 μL) are applied. After incubation, the filters are taken out (90 minutes for BaF/3 cells and 30 minutes for PMN in a CO2 incubator). A Microlite luminometer plate is used to observe the migrated cells in the bottom wells. Each well is then filled with 25 μL of ATPlite one-step. The luminescence intensity is measured with a luminometer following a 10-minute incubation period at room temperature.
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| Animal Protocol |
Mice: The mice utilized are male BALB/c strains weighing 20–25 grams. Isotonic (0.9%) saline (50 μL) is injected intraperitoneally into control mice. When administered orally by gavage two hours prior to and four hours following each intranasal administration of lipopolysaccharide (LPS), napraxixin (0.1–10 mg/kg, p.o.) is suspended in 0.4% methylcellulose. 0.4% methylcellulose (10 mL/kg) is given to control animals. Four Navarixin or vehicle dosages are administered in total[1].
Rats: We utilize male 200 g Sprague-Dawley rats. A volume of 100 μL of isotonic saline is given to control animals. Orally administered two hours prior to the LPS challenge, navixin (0.1-3 mg/kg, p.o.) is suspended in a 0.4% methylcellulose vessel. 10 mL/kg of oral methylcellulose is given to control rats. In these experiments, either the vehicle or Navarixin is administered once[1]. |
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| References |
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| Molecular Formula |
C21H23N3O5
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| Molecular Weight |
397.43
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| Exact Mass |
397.16
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| Elemental Analysis |
C, 63.47; H, 5.83; N, 10.57; O, 20.13
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| CAS # |
473727-83-2
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| Related CAS # |
862464-58-2 (hydrate); 473727-83-2
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| Appearance |
White to off-white solid powder
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| SMILES |
CC[C@H](C1=CC=C(O1)C)NC2=C(C(=O)C2=O)NC3=CC=CC(=C3O)C(=O)N(C)C
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| InChi Key |
RXIUEIPPLAFSDF-CYBMUJFWSA-N
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| InChi Code |
InChI=1S/C21H23N3O5/c1-5-13(15-10-9-11(2)29-15)22-16-17(20(27)19(16)26)23-14-8-6-7-12(18(14)25)21(28)24(3)4/h6-10,13,22-23,25H,5H2,1-4H3/t13-/m1/s1
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| Chemical Name |
2-hydroxy-N,N-dimethyl-3-[[2-[[(1R)-1-(5-methylfuran-2-yl)propyl]amino]-3,4-dioxocyclobuten-1-yl]amino]benzamide
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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) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.29 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 25.0 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: 2.5 mg/mL (6.29 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 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: ≥ 2.5 mg/mL (6.29 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: ≥ 2.5 mg/mL (6.29 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 5: ≥ 2.5 mg/mL (6.29 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.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. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5162 mL | 12.5808 mL | 25.1617 mL | |
| 5 mM | 0.5032 mL | 2.5162 mL | 5.0323 mL | |
| 10 mM | 0.2516 mL | 1.2581 mL | 2.5162 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 |
| NCT00684593 | Completed | Drug: Navarixin 10 mg Other: Placebo |
Psoriasis | Merck Sharp & Dohme LLC | June 1, 2007 | Phase 2 |
| NCT00688467 | Completed | Drug: Navarixin Drug: Placebo |
Asthma | Merck Sharp & Dohme LLC | June 1, 2008 | Phase 2 |
| NCT01006616 | Completed | Drug: Navarixin Drug: Placebo Drug: Rescue medication |
COPD | Merck Sharp & Dohme LLC | October 1, 2009 | Phase 2 |
| NCT00632502 | Completed | Drug: Navarixin Drug: Placebo Drug: Rescue medication |
Neutrophilic Asthma | Merck Sharp & Dohme LLC | May 1, 2008 | Phase 2 |
| NCT03473925 | Completed | Drug: Navarixin Biological: Pembrolizumab |
Solid Tumors Non-small Cell Lung Cancer |
Merck Sharp & Dohme LLC | April 10, 2018 | Phase 2 |
 CXCR2 mRNA expression in colorectal cancer HCT116 and E2 xenografts and the influence of CXCR2 knockdown in colorectal cancer on growth of cells treated with oxaliplatin.Mol Cancer Ther.2012 Jun;11(6):1353-64. |
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 SCH-527123 decreases cell proliferation, migration, and invasion and increases apoptosis in colorectal cancer cells.Mol Cancer Ther.2012 Jun;11(6):1353-64. |
 SCH-527123 combined with oxaliplatin synergistically suppresses colorectal cancer cell proliferation and survival.Mol Cancer Ther.2012 Jun;11(6):1353-64. |
 SCH-527123 in combination with oxaliplatin modulates protein expression of IL-8, PARP, BCL-2/BAX, and decreased NF-κB/Akt/MAPK signaling activity in colorectal cancer cells.Mol Cancer Ther.2012 Jun;11(6):1353-64. |
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 Antitumor activity of SCH-527123 combined with oxaliplatin in HCT116 and E2 xenografts.Mol Cancer Ther.2012 Jun;11(6):1353-64. |
 SCH-527123 in combination with oxaliplatin significantly suppressed NF-κB/Akt/MAPK downstream signaling and angiogenic activity in HCT116 and E2 xenografts.Mol Cancer Ther.2012 Jun;11(6):1353-64. |
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