product name SB225002
Description: SB225002 is a novel, potent, and selective CXCR2 antagonist with IC50 of 22 nM for inhibiting interleukin IL-8 binding to CXCR2, it shows > 150-fold selectivity over the other 7-TMRs tested. SB225002 promotes mitotic catastrophe in chemo-sensitive and -resistant ovarian cancer cells independent of p53 status in vitro. SB225002 induces apoptosis in both wild-type and p53-deficient ovarian cancer (OVCA) cells through alternative mechanisms.
References: J Biol Chem. 1998 Apr 24;273(17):10095-8; Cancer Res. 2006 Mar 15;66(6):3071-7; Surgery. 2014 Apr;155(4):640-9.
352.14
Formula
C13H10BrN3O4
CAS No.
182498-32-4
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 70 mg/mL (198.7 mM)
Water: <1 mg/mL
Ethanol: 3 mg/mL warmed (8.5 mM)
Solubility (In vivo)
2% DMSO+Castor oil: 10mg/mL
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19409543
| In Vitro |
In vitro activity: In vitro, SB225002 inhibits GROα-stimulated calcium mobilization, and potently inhibits human and rabbit neutrophil chemotaxis induced by both IL-8 and GROalpha. SB 225002 substantially reduces the levels of phosphorylated ERK1/2, and decreases cell proliferation in WHCO1 cells. SB225002 also shows the antitumor activity as a microtubule inhibitor. Kinase Assay: Assays are performed in 96-well microtiter plates where the reaction mixture contains 1.0 μg/ml membrane protein in 20 mM Bis-Tris-propane, pH 8.0, with 1.2 mM MgSO4, 0.1 mM EDTA, 25 mM NaCl, and 0.03% CHAPS and SB 225002 (10 mM stock in Me2SO) added at the indicated concentrations, the final Me2SO concentration is <1% under standard binding conditions. Binding is initiated by addition of 0.25 nM 125I-IL-8 (2,200 Ci/mmol). After 1-h incubation at room temperature the plate is harvested using a Tomtec 96-well harvester onto a glass fiber filtermat blocked with 1% polyethyleneimine, 0.5% BSA and washed three times with 25 mM NaCl, 10 mM Tris·HCl, 1 mM MgSO4, 0.5 mM EDTA, 0.03% CHAPS, pH 7.4. The filter is dried, sealed in a sample bag containing 10 ml of Wallac 205 Betaplate liquid scintillation fluid, and counted with a Wallac 1205 Betaplate liquid scintillation counter. Cell Assay: Three esophageal squamous cell carcinoma cell lines WHCO1, WHCO5, and WHCO6 originally established from surgical biopsies of primary esophageal squamous cell carcinomas are cultured in DMEM containing 10% FCS at 37°C in a humidified atmosphere of 5% CO2. MTT assays are carried out using the Cell Proliferation kit I. Briefly, 1.5 × 103 cells are plated in 96-well plates in a final volume of 180 μL DMEM per well. SB 225002 (antagonist of CXCR2, 400 nM) is added to cells and 0.001% DMSO (solvent) is added as a control. After the indicated incubation period, 18 μL of the MTT labeling reagent (final concentration 0.5 mg/mL) is added to each well and incubated for 4 hours in a humidified atmosphere. One hundred eighty microliters of the solubilization solution are added to each well and the plates were left overnight at 37°C. The spectrophotometric absorbance of samples is measured at 595 nm using a microtiter plate reader. |
|---|---|
| In Vivo | In rabbits, SB225002 selectively blocks IL-8-induced neutrophil margination. In mouse intrahepatic cholangiocellular carcinoma model, SB225002 (1 mg/kg i.p.) suppresses the growth of transplanted subcutaneous tumors. In addition, SB225002 also displays long-lasting antinociceptive effects, and reduces TNBS-induced colitis in mouse models. |
| Animal model | Rabbits |
| Formulation & Dosage | Dissolved in DMSO; 5.5 μg/kg/min; Cannula in the external jugular vein |
| References | J Biol Chem. 1998 Apr 24;273(17):10095-8; Cancer Res. 2006 Mar 15;66(6):3071-7; Surgery. 2014 Apr;155(4):640-9. |
