CP-105,696

中文名称:

CP-105,696

中文同义词:

英文名称:

CP-105,696

英文同义词:

CP-105,696;1-[(3S,4R)-4-hydroxy-3-[(4-phenylphenyl)methyl]-3,4-dihydro-2H-chromen-7-yl]cyclopentane-1-carboxylic acid;1-((3S,4R)-3-([1,1-biphenyl]-4-ylmethyl)-4-hydroxychroman-7-yl)cyclopentane-1-carboxylic acid;CP 105696; CP105696; CP-105696; UNII-Z7354TW4BM; PFIZER 105696;Pfizer 105696;UNII-Z7354TW4BM;Cyclopentanecarboxylic acid, 1-[(3S,4R)-3-([1,1-biphenyl]-4-ylmethyl)-3,4-dihydro-4-hydroxy-2H-1-benzopyran-7-yl]-;CP-105,696 >=98% (HPLC)

CAS号:

158081-99-3

分子式:

C28H28O4

分子量:

428.52

EINECS号:

相关类别:

API

Mol文件:

158081-99-3.mol

沸点 

651.2±55.0 °C(Predicted)

密度 

1.252±0.06 g/cm3(Predicted)

储存条件 

room temp

形态

powder

酸度系数(pKa)

4.35±0.20(Predicted)

颜色

white to beige

生物活性

CP-105696 是一个有效的、白三烯 B4 (LTB4) 受体的选择性拮抗剂，其 IC50 值为 8.42 nM。

靶点

LTB 4 8.42±0.26 nM (IC 50 )

LTB 4 8.42±0.26 nM (IC 50 )

体外研究

CP-105696 is a structurally novel, selective and potent LTB 4 receptor antagonist. In vitro, CP-105696 inhibits [ 3 H]LTB 4 (0.3 nM) binding to high-affinity LTB 4 receptors on human neutrophils with an lC 50 value of 8.42±0.26 nM. Scatchard analyses of [ 3 H]LTB 4 binding to these high-affinity receptors indicate that CP-105696 acts as a noncompetitive antagonist. CP-105696 inhibits human neutrophil chemotaxis mediated by LTB 4 (5 nM) in a noncompetitive manner with an IC 50 value of 5.0±2.0 nM. Scatchard analyses of [ 3 H]LTB 4 binding to low-affinity receptors on neutrophils indicate that CP-105696 acts as a competitive antagonist at this receptor, and inhibition of LTB 4 -mediated CD11b upregulation on human neutrophils is competitively inhibited by CP-105696 (pA 2 =8.03±0.19). CP-105696 at 10 μM does not inhibit either human neutrophil chemotaxis or CD11b upregulation mediated through alternate (i.e., C5a, lL-8, PAF) G-protein coupled chemotactic factor receptors. In isolated human monocytes, LTB 4 (5 nM)-mediated Ca 2+ mobilization is inhibited by CP-105696 with an lC 50 value of 940±70 nM.

体内研究

At a dose of 50 mg/kg/day (28 days), B10.BR (H2k) allografts transplanted into C57Bl/6 (H2b) recipients are significantly protected, as reflected by the mean survival time versus control grafts (27±20 days [n=10] vs. 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 (33±23 days [n=9]; P=0.0026), but CP-105696 at 10 mg/kg/day does not (18±16 days [n=8]; P=0.1433). Syngeneic grafts survive indefinitely (n=11). Immunohistological evaluation of allografts at rejection reveals a mononuclear cell infiltrate composed primarily 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 demonstrat a selective reduction in β2-integrin (Mac-1) expression on monocytes/macrophages, as demonstrated by CD11b staining density compared with allograft controls.