WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H206586
CAS#: 473727-83-2
Description: Navarixin, also known as SCH527123, PS291822 and MK-7123, is a potent CXCR2 antagonist. SCH-527123 shows antitumor activity and sensitizes cells to oxaliplatin in preclinical colon cancer models. SCH-527123 showed concentration-dependent antiproliferative effects in HCT116, Caco2, and their respective IL-8-overexpressing variants colorectal cancer cell lines. CH-527123 was able to suppress CXCR2-mediated signal transduction as shown through decreased phosphorylation of the NF-κB/mitogen-activated protein kinase (MAPK)/AKT pathway. SCH-527123 treatment decreased tumor growth and microvessel density when compared with vehicle-treated tumors.
Hodoodo Cat#: H206586
Name: Navarixin
CAS#: 473727-83-2
Chemical Formula: C21H23N3O5
Exact Mass: 397.16
Molecular Weight: 397.430
Elemental Analysis: C, 63.47; H, 5.83; N, 10.57; O, 20.13
Related CAS #: 862464-58-2 (hydrate) 473727-83-2
Synonym: SCH527123; SCH-527123; SCH 527123; MK-7123; MK7123; MK 7123; PS291822; PS-291822; PS 291822; Navarixin monohydrate; Navarixin
IUPAC/Chemical Name: (R)-2-hydroxy-N,N-dimethyl-3-((2-((1-(5-methylfuran-2-yl)propyl)amino)-3,4-dioxocyclobut-1-en-1-yl)amino)benzamide
InChi Key: IXBYSXNOKFHHDR-QGZVFWFLSA-N
InChi Code: 1S/C23H26N2O5/c1-5-7-17(18-11-10-13(2)30-18)24-19-16(21(27)22(19)28)12-14-8-6-9-15(20(14)26)23(29)25(3)4/h6,8-11,17,24,26H,5,7,12H2,1-4H3/t17-/m1/s1
SMILES Code: O=C(N(C)C)C1=CC=CC(NC2=C(N[C@@H](C3=CC=C(C)O3)CC)C(C2=O)=O)=C1O
Appearance: White to off-white 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: Soluble in DMSO (>40mg/mL)
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: | Navarixin (SCH 527123) is a potent, allosteric and orally active antagonist of both CXCR1 and CXCR2, with Kd values of 41 nM for cynomolgus CXCR1 and 0.20 nM, 0.20 nM, 0.08 nM for mouse, rat and cynomolgus monkey CXCR2, respectively. |
In vitro activity: | Sch527123 inhibited chemokine binding to (and activation of) CXCR1 and CXCR2 in an insurmountable manner and, as such, is categorized as an allosteric antagonist. Sch527123 inhibited neutrophil chemotaxis and myeloperoxidase release in response to CXCL1 and CXCL8 but had no effect on the response of these cells to C5a or formyl-methionyl-leucyl-phenylalanine. The pharmacological specificity of Sch527123 was confirmed by testing in a diversity profile against a panel of enzymes, channels, and receptors. To measure compound affinity, Sch527123 was characterized in both equilibrium and nonequilibrium binding analyses. Sch527123 binding to CXCR1 and CXCR2 was both saturable and reversible. Although Sch527123 bound to CXCR1 with good affinity (K(d) = 3.9 +/- 0.3 nM), the compound is CXCR2-selective (K(d) = 0.049 +/- 0.004 nM). Taken together, these data show that Sch527123 represents a novel, potent, and specific CXCR2 antagonist with potential therapeutic utility in a variety of inflammatory conditions. Reference: J Pharmacol Exp Ther. 2007 Aug;322(2):477-85. https://jpet.aspetjournals.org/content/322/2/477.long |
In vivo activity: | Oral treatment with Sch527123 blocked pulmonary neutrophilia (ED(50) = 1.2 mg/kg) and goblet cell hyperplasia (32-38% inhibition at 1-3 mg/kg) in mice following the intranasal lipopolysaccharide (LPS) administration. In rats, Sch527123 suppressed the pulmonary neutrophilia (ED(50) = 1.8 mg/kg) and increase in bronchoalveolar lavage (BAL) mucin content (ED(50) =<0.1 mg/kg) induced by intratracheal (i.t.) LPS. Sch527123 also suppressed the pulmonary neutrophilia (ED(50) = 1.3 mg/kg), goblet cell hyperplasia (ED(50) = 0.7 mg/kg), and increase in BAL mucin content (ED(50) = <1 mg/kg) in rats after i.t. administration of vanadium pentoxide. In cynomolgus monkeys, Sch527123 reduced the pulmonary neutrophilia induced by repeat bronchoscopy and lavage (ED(50) = 0.3 mg/kg). Therefore, Sch527123 may offer benefit for the treatment of inflammatory lung disorders in which pulmonary neutrophilia and mucus hypersecretion are important components of the underlying disease pathology. Reference: J Pharmacol Exp Ther. 2007 Aug;322(2):486-93. https://jpet.aspetjournals.org/content/322/2/486.long |
Solvent | Max Conc. mg/mL | Max Conc. mM | |
---|---|---|---|
Solubility | |||
Soluble in DMSO | 50.0 | 125.80 |
The following data is based on the product molecular weight 397.43 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.
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. Gonsiorek W, Fan X, Hesk D, Fossetta J, Qiu H, Jakway J, Billah M, Dwyer M, Chao J, Deno G, Taveras A, Lundell DJ, Hipkin RW. Pharmacological characterization of Sch527123, a potent allosteric CXCR1/CXCR2 antagonist. J Pharmacol Exp Ther. 2007 Aug;322(2):477-85. doi: 10.1124/jpet.106.118927. Epub 2007 May 11. PMID: 17496166. 2. Ning Y, Labonte MJ, Zhang W, Bohanes PO, Gerger A, Yang D, Benhaim L, Paez D, Rosenberg DO, Nagulapalli Venkata KC, Louie SG, Petasis NA, Ladner RD, Lenz HJ. The CXCR2 antagonist, SCH-527123, shows antitumor activity and sensitizes cells to oxaliplatin in preclinical colon cancer models. Mol Cancer Ther. 2012 Jun;11(6):1353-64. doi: 10.1158/1535-7163.MCT-11-0915. Epub 2012 Mar 5. PMID: 22391039. 3. Chapman RW, Minnicozzi M, Celly CS, Phillips JE, Kung TT, Hipkin RW, Fan X, Rindgen D, Deno G, Bond R, Gonsiorek W, Billah MM, Fine JS, Hey JA. A novel, orally active CXCR1/2 receptor antagonist, Sch527123, inhibits neutrophil recruitment, mucus production, and goblet cell hyperplasia in animal models of pulmonary inflammation. J Pharmacol Exp Ther. 2007 Aug;322(2):486-93. doi: 10.1124/jpet.106.119040. Epub 2007 May 11. PMID: 17496165. 4. Ning Y, Labonte MJ, Zhang W, Bohanes PO, Gerger A, Yang D, Benhaim L, Paez D, Rosenberg DO, Nagulapalli Venkata KC, Louie SG, Petasis NA, Ladner RD, Lenz HJ. The CXCR2 antagonist, SCH-527123, shows antitumor activity and sensitizes cells to oxaliplatin in preclinical colon cancer models. Mol Cancer Ther. 2012 Jun;11(6):1353-64. doi: 10.1158/1535-7163.MCT-11-0915. Epub 2012 Mar 5. PMID: 22391039. |
In vitro protocol: | 1. Gonsiorek W, Fan X, Hesk D, Fossetta J, Qiu H, Jakway J, Billah M, Dwyer M, Chao J, Deno G, Taveras A, Lundell DJ, Hipkin RW. Pharmacological characterization of Sch527123, a potent allosteric CXCR1/CXCR2 antagonist. J Pharmacol Exp Ther. 2007 Aug;322(2):477-85. doi: 10.1124/jpet.106.118927. Epub 2007 May 11. PMID: 17496166. 2. Ning Y, Labonte MJ, Zhang W, Bohanes PO, Gerger A, Yang D, Benhaim L, Paez D, Rosenberg DO, Nagulapalli Venkata KC, Louie SG, Petasis NA, Ladner RD, Lenz HJ. The CXCR2 antagonist, SCH-527123, shows antitumor activity and sensitizes cells to oxaliplatin in preclinical colon cancer models. Mol Cancer Ther. 2012 Jun;11(6):1353-64. doi: 10.1158/1535-7163.MCT-11-0915. Epub 2012 Mar 5. PMID: 22391039. |
In vivo protocol: | 1. Chapman RW, Minnicozzi M, Celly CS, Phillips JE, Kung TT, Hipkin RW, Fan X, Rindgen D, Deno G, Bond R, Gonsiorek W, Billah MM, Fine JS, Hey JA. A novel, orally active CXCR1/2 receptor antagonist, Sch527123, inhibits neutrophil recruitment, mucus production, and goblet cell hyperplasia in animal models of pulmonary inflammation. J Pharmacol Exp Ther. 2007 Aug;322(2):486-93. doi: 10.1124/jpet.106.119040. Epub 2007 May 11. PMID: 17496165. 2. Ning Y, Labonte MJ, Zhang W, Bohanes PO, Gerger A, Yang D, Benhaim L, Paez D, Rosenberg DO, Nagulapalli Venkata KC, Louie SG, Petasis NA, Ladner RD, Lenz HJ. The CXCR2 antagonist, SCH-527123, shows antitumor activity and sensitizes cells to oxaliplatin in preclinical colon cancer models. Mol Cancer Ther. 2012 Jun;11(6):1353-64. doi: 10.1158/1535-7163.MCT-11-0915. Epub 2012 Mar 5. PMID: 22391039. |
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