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Chemical Compound Review

SureCN6154079     2-(3-methoxy-5- methylsulfonyl-4-propoxy...

Synonyms: PDSP1_000667, PDSP1_000668, PDSP2_000658, AC1L3U3S, L-659,989, ...
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Disease relevance of L 659989


High impact information on L 659989

  • Antibody to the CD-18 family of leukocyte adhesion molecules inhibited leukocyte recruitment in response to PAF in the brain (greater than 80%); a similar level of inhibition in the lung required treatment with a combination of a PAF receptor antagonist (L-659,989) and anti-CD18 antibody [1].
  • These functions of PAF appeared to be mediated through the cell surface PAF receptors, as two PAF receptor antagonists, WEB 2086 and L-659,989, blocked both the up-regulation of HB-EGF mRNA and kappa B binding activity induced by PAF [4].
  • Under certain conditions, the PAF receptor antagonist L-659,989 completely blocks the release of Ca2+ from intracellular stores, suggesting a complete block of the receptor-mediated response [5].
  • Furthermore, L-659,989 (10 microM), as well as PAF (1 microM), inhibited specific [3H]PAF binding in LPS-treated but not in untreated cells [6].
  • We also found that the platelet-activating factor receptor antagonists WEB 2086 and L-659,989 inhibit the oxidized LDL stimulation of PLD, suggesting a role for platelet-activating factor receptor in this process [7].

Biological context of L 659989


Anatomical context of L 659989

  • The WGA-potentiated specific binding can be specifically inhibited by N-acetylglucosamine, shows identical affinity for PAF agonists and a receptor antagonist, L-659,989, and has an identical Na+ inhibition pattern to non-treated membranes in the absence of WGA [13].
  • It inhibited [3H]PAF binding to either rabbit platelet or rabbit polymorphonuclear leukocyte membranes with an equilibrium inhibition constant (Kl) of 1.1 nM; whereas in human platelet, human polymorphonuclear leukocyte or human lung membranes, L-659,989 was about 10 times less potent with a Kl of 14.3 nM [10].
  • PAF (10 nM) increased intracellular free calcium concentration in human lymphocytes and this effect was inhibited by L-659,989 dose-dependently [14].
  • Stably transfected fibroblasts expressing the cloned cDNA responded to sub-nanomolar PAF stimulation with calcium mobilization, which could be inhibited by the PAF antagonist L-659,989 [15].
  • Utilizing an intact sheep model that involved a 90-min occlusion of the mid-left anterior descending coronary artery followed by 6 hr of reperfusion, a study group that received a specific PAF receptor antagonist (L-659,989, 5 mg/kg) 10 min before reperfusion was compared to a control group that received a saline placebo (n = 8 in each group) [16].

Associations of L 659989 with other chemical compounds

  • The cytosolic free Ca2+ concentration increase was inhibited by the PAF receptor antagonist L-659,989 (10 microM) and by EGTA (2 mM), indicating receptor-dependent Ca2+ influx [6].
  • The decrease in blood flow appeared to require circulating neutrophils and was prevented by dazmegral and the platelet-activating factor (PAF) antagonists WEB 2086 and L-659,989 [17].
  • The 2,5-tritium labeled L-659,989, similar to [3H]PAF, specifically binds to rabbit platelet membranes with an equilibrium dissociation constant (KD) of 1.60 (+/- 0.20) nM in 10 mM MgCl2 [18].
  • Because indomethacin decreases the activity of platelet-activating factor (PAF), vascular rings were treated with two different specific PAF receptor antagonists: L-659,989 and WEB 2170 BS [19].

Gene context of L 659989

  • Furthermore, L-659,989 and PAF inhibited specific 3H-labeled PAF binding in TNF-treated, but not in untreated cells [20].
  • Constriction to ET-1 was also blocked by the PAF antagonist L-659,989 in AA, but not EA [21].
  • To evaluate the involvement of PAF in the process of parturition, we administered the PAF receptor antagonist, L-659,989, to 17-day timed pregnant rats and followed the events of labor and delivery [8].
  • Treatment with L-659,989 significantly increased survival rate, blunted the rise in plasma myocardial depressant factor activity and lowered serum and macrophage levels of tumor necrosis factor (TNF-alpha) [22].
  • We conclude that the use of a specific PAF receptor antagonist, L-659,989, immediately before controlled coronary reflow attenuated the activation of platelets and neutrophils that occurred during reperfusion [16].

Analytical, diagnostic and therapeutic context of L 659989


  1. Differing roles for platelet-activating factor during inflammation of the lung and subarachnoid space. The special case of Streptococcus pneumoniae. Cabellos, C., MacIntyre, D.E., Forrest, M., Burroughs, M., Prasad, S., Tuomanen, E. J. Clin. Invest. (1992) [Pubmed]
  2. Pharmacological manipulation of inflammation in rabbit hydronephrosis: effects of a combined cyclooxygenase/lipoxygenase inhibitor ethoxyquin, a thromboxane synthase inhibitor RS-5186 and a PAF antagonist L-659,989. Spaethe, S.M., Hsueh, W., Needleman, P. J. Pharmacol. Exp. Ther. (1989) [Pubmed]
  3. Protective effects of L-659,989, a platelet-activating factor receptor antagonist, in myocardial ischemia and reperfusion in rats. Ioculano, M., Squadrito, F., Altavilla, D., Canale, P., Campo, G.M., Bussolino, F., Sardella, A., Urna, G., Caputi, A.P. J. Cardiovasc. Pharmacol. (1994) [Pubmed]
  4. Platelet-activating factor stimulates transcription of the heparin-binding epidermal growth factor-like growth factor in monocytes. Correlation with an increased kappa B binding activity. Pan, Z., Kravchenko, V.V., Ye, R.D. J. Biol. Chem. (1995) [Pubmed]
  5. Platelet-activating factor may stimulate both receptor-dependent and receptor-independent increases in [Ca2+] in human airway epithelial cells. Stoll, L.L., Denning, G.M., Kasner, N.A., Hunninghake, G.W. J. Biol. Chem. (1994) [Pubmed]
  6. Bacterial lipopolysaccharide up-regulates platelet-activating factor-stimulated Ca2+ mobilization and eicosanoid release in human Mono Mac 6 cells. Aepfelbacher, M., Ziegler-Heitbrock, H.W., Lux, I., Weber, P.C. J. Immunol. (1992) [Pubmed]
  7. Stimulation of phospholipase D activity by oxidized LDL in mouse peritoneal macrophages. Gómez-Muñoz, A., Martens, J.S., Steinbrecher, U.P. Arterioscler. Thromb. Vasc. Biol. (2000) [Pubmed]
  8. Prolongation of parturition in the pregnant rat following treatment with a platelet activating factor receptor antagonist. Zhu, Y.P., Hoffman, D.R., Hwang, S.B., Miyaura, S., Johnston, J.M. Biol. Reprod. (1991) [Pubmed]
  9. Binding of [3H]SR 27417, a novel platelet-activating factor (PAF) receptor antagonist, to rabbit and human platelets and polymorphonuclear leukocytes. Herbert, J.M., Laplace, M.C., Maffrand, J.P. Biochem. Pharmacol. (1993) [Pubmed]
  10. Biochemical and pharmacological characterization of L-659,989: an extremely potent, selective and competitive receptor antagonist of platelet-activating factor. Hwang, S.B., Lam, M.H., Alberts, A.W., Bugianesi, R.L., Chabala, J.C., Ponpipom, M.M. J. Pharmacol. Exp. Ther. (1988) [Pubmed]
  11. Further characterization of PAF receptor and novel antagonists. Shen, T.Y., Hussaini, I. International journal of tissue reactions. (1990) [Pubmed]
  12. Selective inhibition of vasoconstrictor responses by platelet-activating factor in rat kidney. Handa, R.K., Strandhoy, J.W., Buckalew, V.M. Am. J. Physiol. (1991) [Pubmed]
  13. Wheat germ agglutinin potentiates specific binding of platelet-activating factor to human platelet membranes and induces platelet-activating factor synthesis in intact platelets. Hwang, S.B., Wang, S. Mol. Pharmacol. (1991) [Pubmed]
  14. Specific binding of platelet-activating factor (PAF) by human peripheral blood mononuclear leukocytes. Ng, D.S., Wong, K. Biochem. Biophys. Res. Commun. (1988) [Pubmed]
  15. Characterization of a human cDNA that encodes a functional receptor for platelet activating factor. Ye, R.D., Prossnitz, E.R., Zou, A.H., Cochrane, C.G. Biochem. Biophys. Res. Commun. (1991) [Pubmed]
  16. Platelet-activating factor antagonism attenuates platelet and neutrophil activation and reduces myocardial injury during coronary reperfusion. Ko, W., Lang, D., Hawes, A.S., Zelano, J.A., Isom, O.W., Krieger, K.H. J. Surg. Res. (1993) [Pubmed]
  17. Control of local blood flow in pulmonary inflammation: role for neutrophils, PAF, and thromboxane. Hellewell, P.G., Henson, P.M., Downey, G.P., Worthen, G.S. J. Appl. Physiol. (1991) [Pubmed]
  18. L-659,989: a useful probe in the detection of multiple conformational states of PAF receptors. Hwang, S.B., Lam, M.H. Lipids (1991) [Pubmed]
  19. Platelets enhance anoxic contraction of rat aortic rings through platelet-activating factor-dependent mechanism. Yang, B.C., Chandna, V.K., Lawson, D.L., Mehta, J.L. J. Cardiovasc. Pharmacol. (1993) [Pubmed]
  20. Tumor necrosis factor induces enhanced responses to platelet-activating factor and differentiation in human monocytic Mono Mac 6 cells. Weber, C., Aepfelbacher, M., Haag, H., Ziegler-Heitbrock, H.W., Weber, P.C. Eur. J. Immunol. (1993) [Pubmed]
  21. Sequential agonist activation and site-specific mediation of acute cyclosporine constriction in rat renal arterioles. Lanese, D.M., Falk, S.A., Conger, J.D. Transplantation (1994) [Pubmed]
  22. Platelet activating factor interaction with tumor necrosis factor and myocardial depressant factor in splanchnic artery occlusion shock. Zingarelli, B., Squadrito, F., Ioculano, M., Altavilla, D., Bussolino, F., Campo, G.M., Caputi, A.P. Eur. J. Pharmacol. (1992) [Pubmed]
  23. The role of platelet-activating factor in musculocutaneous flap reperfusion injury. Stotland, M.A., Kerrigan, C.L. Plast. Reconstr. Surg. (1997) [Pubmed]
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