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

MK-7123, Sch-527123, CXCR2/CXCR1 Antagonist

FDS (Fiches de données de sécurité), certificats d’analyse (CoA) et de qualité (CoQ), dossiers, brochures et autres documents disponibles.

Synonymes: 2-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

Primary Target: CXCR2
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      Aperçu

      Replacement Information

      Tableau de caractéristiques principal

      CAS #Empirical Formula
      473727-83-2C₂₁H₂₃N₃O₅
      Description
      Overview

      This product has been discontinued.



      A 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
      Quality LevelMQ100
      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
      Global Trade Item Number
      Référence GTIN
      532283 0

      Documentation

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

      Titre

      Fiche de données de sécurité des matériaux (FDS) 

      Références bibliographiques

      Aperçu de la référence bibliographique
      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

      Titre
      NPI Flyer- Epigenetics and Nuclear Function Feature
      New Products - Antibodies, Small Molecule, Inhibitors

      Informations techniques

      Titre
      White Paper: Further considerations of antibody validation and usage.
      Fiche technique

      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 Protect from light
      +2°C to +8°C
      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.