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Chemical Compound Review

SureCN1651408     ethyl4-methyl-2-[methyl-[4- [(8-methyl-4,7...

Synonyms: BB 882, AC1L1U2C, AC1Q63YV, 139133-26-9, UNII-H14917M9YW
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Disease relevance of BB 882

  • PATIENTS: A total of 290 patients with predicted severe acute pancreatitis previously studied in a trial of lexipafant, recruited from 78 hospitals through 18 centres in the UK [1].
  • Systemic sepsis affected fewer patients in the lexipafant group (13/138 v 4/148; p=0.023) [2].
  • To examine the effects of BB-882, a novel potent PAF receptor antagonist, on general hemodynamics and regional flow distribution in a canine endotoxic shock model, 14 anesthetized and ventilated dogs received 2 mg/kg of Escherichia coli endotoxin intravenously (i.v.) followed by generous fluid resuscitation [3].
  • It is concluded that the PAF receptor antagonist lexipafant has no significant effect on SK-induced hypotension and does not facilitate an accelerated regimen of administration [4].
  • CONCLUSION: The PAF receptor antagonist BB-882 shows efficacy in treating inflammation in an animal model of acute colitis as evidenced by a dose-dependent fall in macroscopic mucosal damage, neutrophil infiltration and reduced generation of inflammatory mediators [5].

Psychiatry related information on BB 882

  • The observed trends toward improvement in neuropsychological test scores warrant the pursuit of a larger and longer efficacy trial to assess the impact of lexipafant on cognitive performance [6].

High impact information on BB 882

  • Hope or hype for lexipafant [7]?
  • METHODS: Data from the international phase III trial of the platelet-activating factor receptor-antagonist Lexipafant were used to develop a 4-variable prognostic model [8].
  • Interleukin 8, a marker of neutrophil activation, and E-selectin, a marker of endothelial damage, decreased more rapidly in the lexipafant group (both p<0.05); however, absolute values were not different between the two groups [2].
  • Treatment with lexipafant 30 min and 6h after pancreatitis reduced severity of pancreatitis-associated intestinal dysfunction, associated with a diminish in systemic concentrations of IL-1 and local leukocyte recruitment [9].
  • CONCLUSION: Treatment with lexipafant and monoclonal antibodies against ICAM-1 or PECAM-1 reduced the severity of pancreatitis-associated gut endothelial dysfunction, and decreased systemic concentrations of IL-1 and local leucocyte recruitment [10].

Chemical compound and disease context of BB 882


Biological context of BB 882


Anatomical context of BB 882


Associations of BB 882 with other chemical compounds

  • METHODS: Following the rectal instillation of formalin 0.75% into male New Zealand White (NZW) rabbits, 0.85 ml of aggregated immunoglobulin was administered i.v. Treatment groups (0.8 mg/kg, n = 6; 2.4 mg/kg, n = 13; 3.2 mg/kg, n = 10) were given bolus doses of BB-882 two-hourly i.v. (control group, n = 25) [5].
  • CONCLUSION: Treatment with NAC, lexipafant, and/or monoclonal antibodies against PECAM-1, inserted at a later stage of I/R, reduced the severity of I/R-associated intestinal dysfunction and decreased the systemic concentrations of IL-1 beta, local leukocyte recruitment (MPO), and partly restored plasma protease inhibitor levels [20].
  • METHODS: Fifty male Sprague-Dawley rats (200-225 g) were divided into five groups each containing 10 rats; group SO: Sham operation group; group I: hepatic ischaemia group; group IR: ischaemia-reperfusion (IR); group M: IR plus pretreatment with molsidomine; group L: IR plus pretreatment with lexipafant [21].
  • A number of PAF antagonists (apafant, lexipafant, BN-52021, SCH-37370, SR-27417, UR-12670) inhibited [3H]apafant binding with slopes near unity and with a rank order of potency in good agreement with their ability to inhibit PAF-induced rabbit platelet aggregation, suggesting that the sites labelled are functional PAF receptors [22].

Gene context of BB 882

  • Lexipafant treatment significantly reduced serum IL-8 (P = 0.038), and IL-6 declined on day 1 [23].
  • Plasma PMNE-alpha 1-AT complexes peaked on day 1; the gradual fall to baseline over 5 days observed in controls did not occur in patients given Lexipafant [23].
  • Furthermore, Lexipafant, a PAF-receptor (PAF-R) antagonist significantly suppressed the mRNA level and the secretion of apoM in HepG2 cells in a dose-dependent manner [16].
  • RESULTS: Pretreatment with lexipafant, a potent PAF receptor antagonist, significantly reduced the pancreatitis-induced increase in pancreatic endothelial barrier dysfunction, pancreatic leukocyte recruitment and serum levels of IL-1 beta, although a difference persisted between animals with sham operation and pancreatitis [24].
  • The potent PAF receptor antagonist lexipafant (10 mg) (n=35), or matching placebo (n=36), was administered intravenously over 5 min, in a randomized double-blinded protocol, to consecutive patients about to receive SK for AMI; all but three had inferior MI, because of the preference for strategies other than SK therapy in patients with anterior MI [4].

Analytical, diagnostic and therapeutic context of BB 882

  • METHODS: We conducted a randomised, double blind, placebo controlled, multicentre trial of lexipafant (100 mg/24 hours intravenously for seven days commenced within 72 hours of the onset of symptoms) involving 290 patients with an APACHE II score >6 [2].
  • This study provides a rationale for further clinical trials with the potent PAF antagonist Lexipafant in human acute pancreatitis [23].
  • INTERVENTIONS: Patients received either a loading dose of 4 mg of BB-882 on the first day, followed by an intravenous infusion of 96 mg/24 hrs for up to 120 hrs, or placebo [25].
  • At entry, patients receiving Lexipafant (n = 42) or placebo (n = 41) were matched for age and sex, aetiology, APACHE II score and OFS [23].
  • Pretreatment with BB-882 at the dose used only enhanced mesenteric perfusion [3].


  1. Persistent organ failure during the first week as a marker of fatal outcome in acute pancreatitis. Johnson, C.D., Abu-Hilal, M. Gut (2004) [Pubmed]
  2. Double blind, randomised, placebo controlled study of a platelet activating factor antagonist, lexipafant, in the treatment and prevention of organ failure in predicted severe acute pancreatitis. Johnson, C.D., Kingsnorth, A.N., Imrie, C.W., McMahon, M.J., Neoptolemos, J.P., McKay, C., Toh, S.K., Skaife, P., Leeder, P.C., Wilson, P., Larvin, M., Curtis, L.D. Gut (2001) [Pubmed]
  3. Treatment with a platelet-activating factor antagonist has little protective effects during endotoxic shock in the dog. Spapen, H., Zhang, H., Verhaeghe, V., Rogiers, P., Cabral, A., Vincent, J.L. Shock (1997) [Pubmed]
  4. Platelet-activating factor antagonism and streptokinase-induced hypotension in clinical acute myocardial infarction. Taylor, R., Fatovich, D., Hitchcock, T., Morrison, C., Curtis, L. Clin. Sci. (2001) [Pubmed]
  5. Lexipafant (BB-882), a platelet activating factor receptor antagonist, ameliorates mucosal inflammation in an animal model of colitis. Meenan, J., Grool, T.A., Hommes, D.W., Dijkhuizen, S., ten Kate, F.J., Wood, M., Whittaker, M., Tytgat, G.N., van Deventer, S.J. European journal of gastroenterology & hepatology. (1996) [Pubmed]
  6. Randomized trial of the platelet-activating factor antagonist lexipafant in HIV-associated cognitive impairment. Neurological AIDS Research Consortium. Schifitto, G., Sacktor, N., Marder, K., McDermott, M.P., McArthur, J.C., Kieburtz, K., Small, S., Epstein, L.G. Neurology (1999) [Pubmed]
  7. Hope or hype for lexipafant? Abu-Zidan, F.M. Nature (1998) [Pubmed]
  8. Applying Ockham's razor to pancreatitis prognostication: a four-variable predictive model. Spitzer, A.L., Barcia, A.M., Schell, M.T., Barber, A., Norman, J., Grendell, J., Harris, H.W. Ann. Surg. (2006) [Pubmed]
  9. Severity of pancreatitis-associated gut barrier dysfunction is reduced following treatment with the PAF inhibitor lexipafant. Leveau, P., Wang, X., Sun, Z., Börjesson, A., Andersson, E., Andersson, R. Biochem. Pharmacol. (2005) [Pubmed]
  10. Inhibition of platelet-activating factor, intercellular adhesion molecule 1 and platelet endothelial cell adhesion molecule 1 reduces experimental pancreatitis-associated gut endothelial barrier dysfunction. Wang, X., Sun, Z., Börjesson, A., Andersson, R. The British journal of surgery. (1999) [Pubmed]
  11. Lexipafant and acute pancreatitis: a critical appraisal of the clinical trials. Abu-Zidan, F.M., Windsor, J.A. The European journal of surgery = Acta chirurgica. (2002) [Pubmed]
  12. Effect of platelet-activating factor antagonists (BN-52021, WEB-2170, and BB-882) on bacterial translocation in acute pancreatitis. de Souza, L.J., Sampietre, S.N., Assis, R.S., Knowles, C.H., Leite, K.R., Jancar, S., Monteiro Cunha, J.E., Machado, M.C. J. Gastrointest. Surg. (2001) [Pubmed]
  13. Lexipafant inhibits postsurgical adhesion formation. Ozgün, H., Cevikel, M.H., Kozaci, L.D., Sakarya, S. J. Surg. Res. (2002) [Pubmed]
  14. Lexipafant fails to improve survival in severe necrotizing pancreatitis in rats. Rivera, J.A., Werner, J., Warshaw, A.L., Lewandrowski, K.B., Rattner, D.W., Fernández del Castillo, C. Int. J. Pancreatol. (1998) [Pubmed]
  15. Effects of a platelet-activating factor antagonist on lung injury and ventilation after cardiac operation. Taggart, D.P. Ann. Thorac. Surg. (2001) [Pubmed]
  16. Effects of platelet-activating factor, tumor necrosis factor, and interleukin-1alpha on the expression of apolipoprotein M in HepG2 cells. Xu, N., Zhang, X.Y., Dong, X., Ekström, U., Ye, Q., Nilsson-Ehle, P. Biochem. Biophys. Res. Commun. (2002) [Pubmed]
  17. Effects of a new platelet-activating factor antagonist, UR-12670, on several endotoxic shock markers in rats. Balsa, D., Merlos, M., Giral, M., Ferrando, R., Garcia-Rafanell, J., Forn, J. Drugs under experimental and clinical research. (1997) [Pubmed]
  18. Roles of platelet-activating factor, interleukin-1beta and interleukin-6 in intestinal barrier dysfunction induced by mesenteric arterial ischemia and reperfusion. Sun, Z., Wang, X., Lasson, A., Börjesson, A., Leveau, P., Haraldsen, P., Andersson, R. J. Surg. Res. (1999) [Pubmed]
  19. Effects of lexipafant (BB-882), a platelet activating factor receptor antagonist, on liver damage due to bile duct ligation in rats. Oztürk, H., Oztürk, H., Dokucu, A.I., Otcu, S. Acta Gastroenterol. Belg. (2006) [Pubmed]
  20. Effective treatment of gut barrier dysfunction using an antioxidant, a PAF inhibitor, and monoclonal antibodies against the adhesion molecule PECAM-1. Sun, Z., Olanders, K., Lasson, A., Dib, M., Annborn, M., Andersson, K., Wang, X., Andersson, R. J. Surg. Res. (2002) [Pubmed]
  21. Effects of molsidomine and lexipafant in hepatic ischaemia--reperfusion injury. Aldemir, M., Boşnak, M., Al, B., Büyükbayram, H., Taçyildiz, I. Injury. (2004) [Pubmed]
  22. Characterization of [3H]apafant binding to PAF receptor on rabbit platelet membranes: a comparison of a microplate filtration system and a standard method. Balsa, D., Merlos, M., Giral, M., Ferrando, R., García-Rafanell, J., Forn, J. Journal of pharmacological and toxicological methods. (1996) [Pubmed]
  23. Randomized, double-blind phase II trial of Lexipafant, a platelet-activating factor antagonist, in human acute pancreatitis. Kingsnorth, A.N., Galloway, S.W., Formela, L.J. The British journal of surgery. (1995) [Pubmed]
  24. Treatment with lexipafant ameliorates the severity of pancreatic microvascular endothelial barrier dysfunction in rats with acute hemorrhagic pancreatitis. Wang, X., Sun, Z., Börjesson, A., Haraldsen, P., Aldman, M., Deng, X., Leveau, P., Andersson, R. Int. J. Pancreatol. (1999) [Pubmed]
  25. Phase II multicenter clinical study of the platelet-activating factor receptor antagonist BB-882 in the treatment of sepsis. Vincent, J.L., Spapen, H., Bakker, J., Webster, N.R., Curtis, L. Crit. Care Med. (2000) [Pubmed]
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