Disease relevance of SR27417

• Stasis-induced thrombosis performed in the rabbit jugular vein was enhanced in a dose-dependent manner by the prior i.v. administration of LPS (0.05 to 100 micrograms/ kg, i.v.). SR 27417 administered simultaneously with LPS prevented thrombus formation with an ED50 value of 0.1 +/- 0.04 mg/kg [1].
• These results confirm that PAF plays a major role in the development of cutaneous anaphylaxis and that SR 27417 may be an effective prophylactic drug [2].
• SR 27417, a potent PAF receptor antagonist injected iv, reduced venous thrombosis in a dose-dependent manner (14, 29 and 63% inhibition after 1, 3 and 6 mg/kg respectively) [3].
• Effect of SR 27417, a novel PAF antagonist on antigen-induced hypotension in the rat [4].
• These results therefore confirm that PAF plays a major role in septic shock and that SR 27417 may be an effective prophylactic as well as a potent curative drug [5].

High impact information on SR27417

• CT-induced CHO elongation was blocked by specific PAF receptor antagonists, BN52021 and SR27417 [6].
• We report that the specific PAF receptor antagonists BN 52021 and SR 27417 inhibit the effects of cholera toxin on intestinal secretion in rabbit ileal loops in vivo and on the cytoskeleton of Chinese hamster ovary cells in vitro [7].
• In human colonic PCmsrc cells transformed by c-src oncogene, the hepatocyte growth factor (HGF)-dependent invasiveness of collagen gels was abolished by 0.1 microM PAF and restored by the PAF-R antagonists WEB2086 and SR27417 [8].
• SR 27417, a PAF receptor antagonist, blocked PAF-induced kappa B binding activity but not that induced by tumor necrosis factor-alpha (TNF alpha) [9].
• SR 27417, the first member of a newly developed PAF antagonist series, competitively displaced [3H]PAF from its binding sites on guinea-pig tracheal epithelial cells with a Ki of 100 +/- 3 pM (n = 3) [10].

Chemical compound and disease context of SR27417

• In guinea pigs, yangambin inhibited PAF-induced thrombocytopenia but did not affect leukocytopenia whereas SR 27417 afforded complete protection against both PAF-induced thrombocytopenia and leukocytopenia [11].

Biological context of SR27417

• SR 27417 potently inhibited PAF-induced aggregation of rabbit and human platelets in vitro (IC50 = 0.10 and 0.50 nM, respectively) but had no effect on the action of other platelet-aggregating agents [12].
• SR 27417 displayed marked in vitro inhibition of PAF-induced oxidative burst in guinea pig macrophages (IC50 = 32 nM) [12].
• Inhibitory effects of SR 27417 were determined at thirteen different concentrations (0.1-400 nM) by using the dose-response curves of PAF on calf platelet aggregation [13].

Anatomical context of SR27417

• In conclusion, these data suggest that tracheal epithelial cells contain PAF-specific receptors and indicate that SR 27417 is an extremely potent PAF-receptor antagonist, as well as being a suitable radioligand for labelling PAF receptors on intact cells [10].
• In conclusion, these data indicate that SR 27417 appears to be one of the most potent PAF receptor antagonists yet described, as well as a suitable radioligand for labelling PAF receptors on intact blood cells [14].
• Effect of SR 27417 on the binding of [3H]PAF to rabbit and human platelets and human polymorphonuclear leukocytes [15].
• In addition, a dose of apafant (1.5 mg/kg) that showed almost maximal effect when given 30 min before PAF, had lost most of its protective action by 3 h, while SR 27417 at a comparably effective dose (0.5 mg/kg) retained substantial ability to prevent gut lesions in all the GI tract segments investigated, 18 h after administration [16].
• The platelet-specific agonist collagen (1 microg/mL) increased leukocyte CD11b expression from 2.94+/-0.52 to 3.81+/-0.58 (P:<0. 05); this was not inhibited by the thromboxane A(2) receptor antagonist ICI 192.605 or the PAF antagonist SR27417 [17].

Associations of SR27417 with other chemical compounds

• C16-PAF, lyso-PAF, enantio-PAF, SR 27417 and other PAF-receptor antagonists had Ki values which were nearly identical for both [3H]PAF and [3H]SR 27417, demonstrating that in guinea-pig tracheal epithelial cells they have the same binding sites [10].
• IC50 values for PAF-induced platelet aggregation were 80, 35, 50 and 1250 micrograms/kg, 1, 3, 24 and 72 h after oral intake of SR 27417 respectively [18].

Gene context of SR27417

• Biochemical and pharmacological activities of SR 27417, a highly potent, long-acting platelet-activating factor receptor antagonist [12].

Analytical, diagnostic and therapeutic context of SR27417

• After i.v. or oral administration (1 and 5 mg/kg respectively) SR 27417 had an extended duration of activity (between 72 and 96 h) [2].

References