| Name | CP-105696 |
| Description | CP-105696 is a potent and selective leukotriene B4 (LTB4) receptor antagonist used to study allograft rejection. |
| In vitro | CP-105696 is a structurally novel, selective, and potent LTB4 receptor antagonist. In vitro, it inhibits [3H]LTB4 (0.3 nM) binding to high-affinity LTB4 receptors on human neutrophils with an IC50 of 8.42±0.26 nM and acts as a noncompetitive antagonist. It noncompetitively inhibits LTB4 (5 nM)-mediated human neutrophil chemotaxis with an IC50 of 5.0±2.0 nM. For low-affinity receptors on neutrophils, CP-105696 acts as a competitive antagonist according to Scatchard analyses. Additionally, it competitively inhibits LTB4-mediated CD11b upregulation on human neutrophils (pA2=8.03±0.19). At 10 μM, CP-105696 does not inhibit human neutrophil chemotaxis or CD11b upregulation mediated by other G-protein coupled receptors (e.g., C5a, IL-8, PAF). In isolated human monocytes, it inhibits LTB4 (5 nM)-mediated Ca2+ mobilization with an IC50 of 940±70 nM[2]. |
| In vivo | At a dose of 50 mg/kg/day for 28 days, B10.BR (H2k) allografts transplanted into C57Bl/6 (H2b) recipients show significant protection, with mean survival time of 27±20 days (n=10) compared to control grafts' 12±6 days (n=14); P=0.0146. Using an induction protocol (day -1 to day 3), CP-105696 at 100 mg/kg/day significantly prolongs allograft survival to 33±23 days (n=9; P=0.0026), whereas at 10 mg/kg/day, it does not (18±16 days; n=8; P=0.1433). Syngeneic grafts exhibit indefinite survival (n=11). Immunohistological evaluation of allografts at rejection reveals a mononuclear cell infiltrate primarily composed of CD3+ and CD11b+ (Mac-1+) cells, which are infrequent in syngeneic grafts. Allografts from mice treated with CP-105696 at 50 or 100 mg/kg/day show a selective reduction in β2-integrin (Mac-1) expression on monocytes/macrophages, as indicated by CD11b staining density compared with allograft controls[1]. |
| Storage | Shipping with blue ice/Shipping at ambient temperature. |
| Solubility Information | DMSO : 80 mg/mL (186.69 mM), Sonication is recommended.
10% DMSO+40% PEG300+5% Tween 80+45% Saline : 3.3 mg/mL (7.7 mM), Sonication is recommended.
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| Keywords | plusmn | LTB4 | CP-105696 | CP105696 | CP 105696 |
| Inhibitors Related | Montelukast sodium | L 674573 | Olsalazine disodium | Pirodomast | Pranlukast | CGP 35949 | Bestatin | Tebufelone | ABT-080 | LTβR-IN-1 | Darbufelone mesylate | Ticolubant |
| Related Compound Libraries | Bioactive Compound Library | ReFRAME Related Library | Inhibitor Library | Immunology/Inflammation Compound Library | Bioactive Compounds Library Max | GPCR Compound Library |
United States
