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Chemical Compound Review

VML-295     sodium2-[3-[3-[2-ethyl-4-(4- fluorophenyl)...

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Disease relevance of Etalocib


High impact information on Etalocib


Biological context of Etalocib

  • Simultaneously, LY293111 induced caspase-dependent apoptosis via activation of the intrinsic pathway, including early loss of mitochondrial inner transmembrane potential and the production of reactive oxygen species (ROS), cleavage of caspases-9, -3, poly ADP-ribose polymerase (PARP) and X-linked inhibitor of apoptosis [3].
  • 1. The effects of orally administered LY293111 on ex vivo neutrophil Mac-1 upregulation were determined in a total of 24 healthy male subjects within three study periods [6].

Anatomical context of Etalocib


Associations of Etalocib with other chemical compounds

  • There was a significant reduction in the concentration of myeloperoxidase (MPO) with both placebo (16 (6.6) ng/ml) and LY293111 (3.5 (1.8) ng/ml) and of LTB4 (placebo 4.6 (1.2) pg/ml, LY293111 2.2 (0.2) pg/ml) [11].
  • Subjects with an established early (EAR) and late asthmatic response (LAR) to allergen at screening received oral LY293111 in a dose of 112 mg three times daily for seven days or placebo before further allergen challenge [11].
  • LY293111 was not effective in blocking human neutrophil activation responses induced by N-formyl-methionyl-leucyl-phenylalanine (fMLP), platelet-activating factor (PAF), human recombinant endothelial interleukin-8 (IL-8) or human recombinant complement component 5a (C5a) [7].
  • This was consistent with the observed disparity in half-lives between LY293111 and total radioactivity in rats and monkeys, and is likely due to covalent modification of proteins by the acyl glucuronide [10].

Gene context of Etalocib


Analytical, diagnostic and therapeutic context of Etalocib


  1. Phase I and pharmacokinetic study of LY293111, an orally bioavailable LTB4 receptor antagonist, in patients with advanced solid tumors. Schwartz, G.K., Weitzman, A., O'Reilly, E., Brail, L., de Alwis, D.P., Cleverly, A., Barile-Thiem, B., Vinciguerra, V., Budman, D.R. J. Clin. Oncol. (2005) [Pubmed]
  2. Leukotriene B4 receptor antagonist LY293111 inhibits proliferation and induces apoptosis in human pancreatic cancer cells. Tong, W.G., Ding, X.Z., Hennig, R., Witt, R.C., Standop, J., Pour, P.M., Adrian, T.E. Clin. Cancer Res. (2002) [Pubmed]
  3. Leukotriene B4 receptor inhibitor LY293111 induces cell cycle arrest and apoptosis in human anaplastic large-cell lymphoma cells via JNK phosphorylation. Zhang, W., McQueen, T., Schober, W., Rassidakis, G., Andreeff, M., Konopleva, M. Leukemia (2005) [Pubmed]
  4. Effect of LY293111 in combination with gemcitabine in colonic cancer. Hennig, R., Ding, X.Z., Tong, W.G., Witt, R.C., Jovanovic, B.D., Adrian, T.E. Cancer Lett. (2004) [Pubmed]
  5. Chemotaxis and activation of human peripheral blood eosinophils induced by pollen-associated lipid mediators. Plötz, S.G., Traidl-Hoffmann, C., Feussner, I., Kasche, A., Feser, A., Ring, J., Jakob, T., Behrendt, H. J. Allergy Clin. Immunol. (2004) [Pubmed]
  6. Inhibition of ex vivo neutrophil activation by oral LY293111, a novel leukotriene B4 receptor antagonist. Marder, P., Spaethe, S.M., Froelich, L.L., Cerimele, B.J., Petersen, B.H., Tanner, T., Lucas, R.A. British journal of clinical pharmacology. (1996) [Pubmed]
  7. Blockade of human neutrophil activation by 2-[2-propyl-3-[3-[2-ethyl-4-(4-fluorophenyl)-5- hydroxyphenoxy]propoxy]phenoxy]benzoic acid (LY293111), a novel leukotriene B4 receptor antagonist. Marder, P., Sawyer, J.S., Froelich, L.L., Mann, L.L., Spaethe, S.M. Biochem. Pharmacol. (1995) [Pubmed]
  8. Pharmacologic actions of the second-generation leukotriene B4 receptor antagonist LY293111: in vitro studies. Jackson, W.T., Froelich, L.L., Boyd, R.J., Schrementi, J.P., Saussy, D.L., Schultz, R.M., Sawyer, J.S., Sofia, M.J., Herron, D.K., Goodson, T., Snyder, D.W., Pechous, P.A., Spaethe, S.M., Roman, C.R., Fleisch, J.H. J. Pharmacol. Exp. Ther. (1999) [Pubmed]
  9. The regulation of CD11b integrin levels on human blood leukocytes and leukotriene B4-stimulated skin by a specific leukotriene B4 receptor antagonist (LY293111). van Pelt, J.P., de Jong, E.M., van Erp, P.E., Mitchell, M.I., Marder, P., Spaethe, S.M., van Hooijdonk, C.A., Kuijpers, A.L., van de Kerkhof, P.C. Biochem. Pharmacol. (1997) [Pubmed]
  10. Preclinical characterization of 2-[3-[3-[(5-ethyl-4'-fluoro-2-hydroxy[1,1'-biphenyl]-4-yl)oxy]propoxy]-2-propylphenoxy]benzoic acid metabolism: in vitro species comparison and in vivo disposition in rats. Perkins, E.J., Cramer, J.W., Farid, N.A., Gadberry, M.G., Jackson, D.A., Mattiuz, E.L., O'Bannon, D.D., Weiss, H.J., Wheeler, W.J., Wood, P.G., Cassidy, K.C. Drug Metab. Dispos. (2003) [Pubmed]
  11. Effect of a leukotriene B4 receptor antagonist, LY293111, on allergen induced responses in asthma. Evans, D.J., Barnes, P.J., Spaethe, S.M., van Alstyne, E.L., Mitchell, M.I., O'Connor, B.J. Thorax (1996) [Pubmed]
  12. Effects of leukotriene B4 receptor antagonist, LY293111Na, on antigen-induced bronchial hyperresponsiveness and leukocyte infiltration in sensitized guinea pigs. Asanuma, F., Kuwabara, K., Arimura, A., Furue, Y., Fleisch, J.H., Hori, Y. Inflamm. Res. (2001) [Pubmed]
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