532283 CXCR2 Antagonist IV, Sch527123 - CAS 473727-83-2 - Calbiochem

532283
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      Overview

      Replacement Information

      Key Specifications Table

      Empirical FormulaCAS #
      C₂₁H₂₃N₃O₅ 473727-83-2

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      5.32283.0001
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          Glass bottle 5 mg
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          Description
          OverviewA cell-permeable, orally active, non-toxic, cyclobutenedione compound with anti-inflammatory properties. Acts as a specific, high-affinity, and potent allosteric antagonist of CXCR2 (IC50 = 2.6 nM for human; Kd = 49, 200, and 80 pM for human, rat, and cynomolgus, respectively). Also exhibits high potency against CXCR1 (IC50 = 36 nM for human, Kd = 3.9 and 41 nM for human and cynomolgus, respectively). Displays excellent selectivity over CXCR3, CCR5, and a large panel of GPCRs, enzymes and ion channels (~ 10 µM). Potently inhibits CXCL1- and CXCL8-induced chemotaxis in human neutrophils (hPMN; IC50 < 1 nM and 16 nM, respectively). Shown to suppress pulmonary neutrophilia (ED50 = 1.3 mg/kg), goblet cell hyperplasia (ED50 = 700 mg/kg), and increase bronchoalveolar lavage (BAL) mucin content (ED50 ≤ 1 mg/kg) in rats subjected to vanadium pentoxide induced pulmonary inflammation. Inhibits melanoma cell proliferation (~ 1 mg/ml) by suppressing the phosphorylation of ERK1/2. Diminishes the invasive potential of melanoma cells and blocks angiogenesis in mice (100 mg/kg, p.o., q.d for 21 days). Exhibits desirable pharmacokinetic properties.

          Please note that the molecular weight for this compound is batch-specific due to variable water content.
          Catalogue Number532283
          Brand Family Calbiochem®
          Synonyms2-Hydroxy-N,N-dimethyl-3-((2-((1(R)-(5-methyl-2-furanyl)propyl)amino)-3,4-dioxo-1-cyclobuten-1-yl)amino)benzamide, (R)-2-Hydroxy-N,N-dimethyl-3-(2-(1-(5-methylfuran-2-yl)propylamino)-3,4-dioxocyclobut-1-enylamino)benzamide, CXCR1 Antagonist, MK-7123, Sch-N, Sch-527123
          References
          ReferencesSeiberling, M., et al. 2013. Int. Immunopharmacol. 17, 178.
          Salchow, K., et al. 2010. Br. J. Pharmacol. 159, 1429.
          Singh, S., et al. 2009. Clin. Cancer Res. 15, 2380.
          Chapman, R.W., et al. 2007. J. Pharmacol. Exp. Ther. 322, 486.
          Gonsiorek, W., et al. 2007. J. Pharmacol. Exp. Ther. 322, 477.
          Dwyer, M.P., et al. 2006. J. Med. Chem. 49, 7603.
          Product Information
          CAS number473727-83-2
          FormYellow solid
          Hill FormulaC₂₁H₂₃N₃O₅
          Chemical formulaC₂₁H₂₃N₃O₅
          ReversibleY
          Applications
          Biological Information
          Primary TargetCXCR2
          Secondary targetCXCR1
          Purity≥97% by HPLC
          Physicochemical Information
          Cell permeableY
          Dimensions
          Materials Information
          Toxicological Information
          Safety Information according to GHS
          Safety Information
          Product Usage Statements
          Storage and Shipping Information
          Ship Code Ambient Temperature Only
          Toxicity Standard Handling
          Storage +2°C to +8°C
          Protect from Light Protect from light
          Do not freeze Ok to freeze
          Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
          Packaging Information
          Packaged under inert gas Packaged under inert gas
          Transport Information
          Supplemental Information
          Specifications

          Documentation

          CXCR2 Antagonist IV, Sch527123 - CAS 473727-83-2 - Calbiochem SDS

          Title

          Safety Data Sheet (SDS) 

          References

          Reference overview
          Seiberling, M., et al. 2013. Int. Immunopharmacol. 17, 178.
          Salchow, K., et al. 2010. Br. J. Pharmacol. 159, 1429.
          Singh, S., et al. 2009. Clin. Cancer Res. 15, 2380.
          Chapman, R.W., et al. 2007. J. Pharmacol. Exp. Ther. 322, 486.
          Gonsiorek, W., et al. 2007. J. Pharmacol. Exp. Ther. 322, 477.
          Dwyer, M.P., et al. 2006. J. Med. Chem. 49, 7603.

          Brochure

          Title
          NPI Flyer- Epigenetics and Nuclear Function Feature (EMD)
          New Products - Antibodies, Small Molecule, Inhibitors

          Technical Info

          Title
          White Paper: Further considerations of antibody validation and usage. (EMD)
          Data Sheet

          Note that this data sheet is not lot-specific and is representative of the current specifications for this product. Please consult the vial label and the certificate of analysis for information on specific lots. Also note that shipping conditions may differ from storage conditions.

          Revision19-December-2014 JSW
          Synonyms2-Hydroxy-N,N-dimethyl-3-((2-((1(R)-(5-methyl-2-furanyl)propyl)amino)-3,4-dioxo-1-cyclobuten-1-yl)amino)benzamide, (R)-2-Hydroxy-N,N-dimethyl-3-(2-(1-(5-methylfuran-2-yl)propylamino)-3,4-dioxocyclobut-1-enylamino)benzamide, CXCR1 Antagonist, MK-7123, Sch-N, Sch-527123
          DescriptionA cell-permeable orally available (plasma Cmax/AUC/dose = 17.0 µM/31.5 µM h-10-24 h/25 mg kg-1/mouse; 5.0 µM/23.0 µM h-10-48 h/10 mg kg-1/rat; 0.9 µM/4.0 µM h-10-48 h/3 mg kg-1/Cynomolgus monkey) cyclobutenedione compound that targets CXCR2 intracellular allosteric site via high affinity interaction (Kd = 49 pM/human, 80 pM/Cynomolgus monkey, 200 pM/ mouse & rat) in a reversible and slowly dissociating manner (k2 = 0.00058 min-1; t1/2 ≈ 22 h; human CXCR2), while exhibiting much reduced affinity toward CXCR1 (Kd = 3.9 nM/human & 41 nM/Cynomolgus monkey) due to a much faster dissociation rate (k2 = 0.141 min-1; t1/2 ≈ 5 min; human CXCR1) and displaying no significant efficacy toward a large panel of GPCRs, enzymes, and ion channels (IC50 >10 µM), including CXCR3 & CCR5. Likewise, Sch527123 is shown exhibit much higher potency against CXCR2- than CXCR1-mediated chemotaxis of Ba/F3 transfectants (IC50/ligand/CXCR2 species = 2.8 nM/3 nM hCXCL8/monkey, 3.4 nM/3 nM rCINC-3/rat, 5.6 nM/mCXCR2/3 nM mMIP-2, <<3 nM/0.1 to 60 nM hCXCL8/human; % inhibition/[Sch527123]/ligand/CXCR1 species = 35%/300 nM/3 nM hCXCL8/ human & 50%/9.667 µM/3 nM hCXCL8/monkey) without affecting C5a- or fMLP-induced human neutrophil chemotaxis. Oral administration is shown to effectively reduce pulmonary neutrophilia in vivo among LPS- or V2O5-treated mice & rats (ED50 1.3 to 1.8 mg/kg), as well as among Cynomolgus monkeys receiving repeat bronchoscopy & lung lavage (ED50 0.3 mg/kg). Also reported to inhibit hCXCL8-dependent human melanoma A375SM chemotaxis & invasion (79% & 69% inhibition, respectively, with 10 ng/mL = 25 nM Sch527123; overnight at 37 °C;10 ng/mL hCXCL8) and effectively suppress A375SM proliferation both in cultures in vitro (31% inhibition by MTT assay post 72 h treatment with 1 µg/mL = 2.5 µM Sch527123) and in mice in vivo (79% inhibition on D50 post cancer cells injection; 100 mg/kg/d p.o. D1 through D22) with concomitant increased apoptotic cells (203% of control) and decreased microvessel density in tumor tissues (55% of control).
          FormYellow solid
          Intert gas (Yes/No) Packaged under inert gas
          CAS number473727-83-2
          Chemical formulaC₂₁H₂₃N₃O₅
          Purity≥97% by HPLC
          SolubilityDMSO (50 mg/ml). Use only fresh DMSO for reconstitution.
          Storage +2°C to +8°C
          Protect from light
          Do Not Freeze Ok to freeze
          Special InstructionsFollowing reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.
          Toxicity Standard Handling
          ReferencesSeiberling, M., et al. 2013. Int. Immunopharmacol. 17, 178.
          Salchow, K., et al. 2010. Br. J. Pharmacol. 159, 1429.
          Singh, S., et al. 2009. Clin. Cancer Res. 15, 2380.
          Chapman, R.W., et al. 2007. J. Pharmacol. Exp. Ther. 322, 486.
          Gonsiorek, W., et al. 2007. J. Pharmacol. Exp. Ther. 322, 477.
          Dwyer, M.P., et al. 2006. J. Med. Chem. 49, 7603.