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Chemical Compound Review

AC1NSKNO     (Z)-7-[(1S,4R,5S,6R)-5-[(2...

Synonyms: SQ-29548, SQ29548, 98672-91-4
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Disease relevance of SQ29548

  • Endothelial migration and corneal angiogenesis are similarly inhibited by a TXA2 receptor antagonist, SQ29548 [1].
  • The blood pressure-lowering effect of SQ29548 in the early phase of aortic coarctation-induced hypertension was positively correlated with the prevailing plasma renin activity and could not be demonstrated in hypertensive rats pretreated with indomethacin [2].
  • Lipoxygenase inhibition (10 microM AA861) alone or in combination with thromboxane receptor antagonism (10 microM SQ29548) had no effect on PAF-induced weight gain [3].
  • Crystalloid-perfused rat hearts that had undergone Langendorff preparation (n = 30) were subjected to 2 hours of global ischemia at 15 degrees C under cardioplegic protection with (n = 15) or without (n = 15) thromboxane A2 receptor antagonist SQ29548 [4].
  • The competition curve for STA2 inhibition of [3H]SQ29548 binding was shifted to the right and was steeper in the presence of GTP gamma S. Pertussis toxin (IAP) elicited ADP-ribosylation of 41KD protein but had no effect on the sensitivity to GTP of the STA2 inhibition of SQ29548 binding or of STA2-induced accumulation of IPs [5].

High impact information on SQ29548


Chemical compound and disease context of SQ29548


Biological context of SQ29548

  • Tyrosine phosphorylation of p27 and p31 in response to collagen, but not thrombin, is prevented by aspirin and the TXA(2) receptor antagonist SQ29548, indicating that the effect of collagen strongly relies on TXA(2) signaling [11].
  • In this experimental setting, the administration of SQ29548 reduced preglomerular vascular resistance selectively [12].
  • SQ29548, a thromboxane receptor antagonist, inhibited the AA-induced platelet aggregation but not TXB(2) production [13].
  • The supernatant did not affect the Kd or Bmax of [125I]PTA-OH or the IC50 of the TXA2/PGH2 antagonist, SQ29548 [14].
  • 2 The four rabbit aorta phenotypes, R1, R2, IR, and NR, were characterized with respect to the rank orders of prostanoid agonist potency, agonist intrinsic activities, and the effects of the thromboxane receptor antagonist SQ29548 [15].

Anatomical context of SQ29548


Associations of SQ29548 with other chemical compounds


Gene context of SQ29548

  • Preincubation of HUVECs with SQ29548, a TXA2 receptor antagonist, dose-dependently inhibited platelet-induced COX-2 expression and prostanoid synthesis [26].
  • However, in contrast to that which occurred in ULTR cells, SQ29548 abolished 8-epiPGF(2alpha) mediated ERK and JNK activation through both TPalpha and TPbeta in HEK 293 cells providing further evidence that 8-epiPGF(2alpha) may signal through alternative receptors, in addition to the TPs, in human uterine ULTR cells [27].
  • The presence of the prostaglandin H2/thromboxane A2 receptor antagonist SQ29548 did not affect arteriolar diameters of control mice but reduced the enhanced arteriolar tone of db/db mice back to control levels (at 80 mm Hg, 80+/-4%) [28].
  • Furthermore, preincubation of whole blood with 75 micro mol L-1 or 150 micromol L(-1) SQ29548, a TxA2 receptor antagonist, completely blocked epinephrine's promoting effect on LPS-induced IL-8 release [29].
  • Furthermore, SQ29548, a thromboxane A2/prostaglandin H2 receptor antagonist, significantly reduced CD40L-enhanced expression of intercellular adhesion molecule-1 [30].

Analytical, diagnostic and therapeutic context of SQ29548


  1. Thromboxane A2 is a mediator of cyclooxygenase-2-dependent endothelial migration and angiogenesis. Daniel, T.O., Liu, H., Morrow, J.D., Crews, B.C., Marnett, L.J. Cancer Res. (1999) [Pubmed]
  2. Role of prostanoids in renin-dependent and renin-independent hypertension. Lin, L., Mistry, M., Stier, C.T., Nasjletti, A. Hypertension (1991) [Pubmed]
  3. Quinolines attenuate PAF-induced pulmonary pressor responses and edema formation. Falk, S., Göggel, R., Heydasch, U., Brasch, F., Müller, K.M., Wendel, A., Uhlig, S. Am. J. Respir. Crit. Care Med. (1999) [Pubmed]
  4. Cardiac-derived thromboxane A2. An initiating mediator of reperfusion injury? Byrne, J.G., Appleyard, R.F., Sun, S.C., Couper, G.S., Sloane, J.A., Laurence, R.G., Cohn, L.H. J. Thorac. Cardiovasc. Surg. (1993) [Pubmed]
  5. Thromboxane A2 activates phospholipase C in astrocytoma cells via pertussis toxin-insensitive G-protein. Nakahata, N., Matsuoka, I., Ono, T., Nakanishi, H. Eur. J. Pharmacol. (1989) [Pubmed]
  6. Hypoxia-reoxygenation triggers coronary vasospasm in isolated bovine coronary arteries via tyrosine nitration of prostacyclin synthase. Zou, M.H., Bachschmid, M. J. Exp. Med. (1999) [Pubmed]
  7. Rat kidney thromboxane receptor: molecular cloning, signal transduction, and intrarenal expression localization. Abe, T., Takeuchi, K., Takahashi, N., Tsutsumi, E., Taniyama, Y., Abe, K. J. Clin. Invest. (1995) [Pubmed]
  8. Effect of thromboxane A2/endoperoxide antagonist SQ29548 on the contractile response to acetylcholine in newborn piglet cerebral arteries. Wagerle, L.C., Busija, D.W. Circ. Res. (1990) [Pubmed]
  9. Mediation of renal vascular effects of epidermal growth factor by arachidonate metabolites. Harris, R.C., Munger, K.A., Badr, K.F., Takahashi, K. FASEB J. (1990) [Pubmed]
  10. High glucose via peroxynitrite causes tyrosine nitration and inactivation of prostacyclin synthase that is associated with thromboxane/prostaglandin H(2) receptor-mediated apoptosis and adhesion molecule expression in cultured human aortic endothelial cells. Zou, M.H., Shi, C., Cohen, R.A. Diabetes (2002) [Pubmed]
  11. P2Y12 ADP receptor-dependent tyrosine phosphorylation of proteins of 27 and 31 kDa in thrombin-stimulated human platelets. Fälker, K., Lange, D., Presek, P. Thromb. Haemost. (2005) [Pubmed]
  12. Angiotensin II influences the renal hemodynamic response to blockade of thromboxane A2 and prostaglandin H2 receptors. Yamaguchi, Y., Fenoy, F.J., Roman, R.J., Nasjletti, A. J. Pharmacol. Exp. Ther. (1992) [Pubmed]
  13. Antiplatelet effect of sanguinarine is correlated to calcium mobilization, thromboxane and cAMP production. Jeng, J.H., Wu, H.L., Lin, B.R., Lan, W.H., Chang, H.H., Ho, Y.S., Lee, P.H., Wang, Y.J., Wang, J.S., Chen, Y.J., Chang, M.C. Atherosclerosis (2007) [Pubmed]
  14. Decrease in agonist affinity for human platelet thromboxane A2/prostaglandin H2 receptors induced by a platelet-derived supernatant. Dorn, G.W., Burch, R.M., Kochel, P.J., Mais, D.E., Halushka, P.V. Biochem. Pharmacol. (1987) [Pubmed]
  15. Individual variations of prostanoid agonist responses in rabbit aorta: evidence for the independent regulation of prostanoid receptor subtypes. Keith, R.A., Salama, A.I. Br. J. Pharmacol. (1987) [Pubmed]
  16. Metabolism of 20-hydroxyeicosatetraenoic acid by cyclooxygenase. Formation and identification of novel endothelium-dependent vasoconstrictor metabolites. Schwartzman, M.L., Falck, J.R., Yadagiri, P., Escalante, B. J. Biol. Chem. (1989) [Pubmed]
  17. Coronary artery constriction by the isoprostane 8-epi prostaglandin F2 alpha. Kromer, B.M., Tippins, J.R. Br. J. Pharmacol. (1996) [Pubmed]
  18. Thromboxane receptor stimulation associated with loss of SKCa activity and reduced EDHF responses in the rat isolated mesenteric artery. Crane, G.J., Garland, C.J. Br. J. Pharmacol. (2004) [Pubmed]
  19. Characterization of signal transduction events stimulated by 8-epi-prostaglandin(PG)F2 alpha in rat aortic rings. Wagner, R.S., Weare, C., Jin, N., Mohler, E.R., Rhoades, R.A. Prostaglandins (1997) [Pubmed]
  20. Implications for repetitive application of acetylcholine in the determination of the mechanisms of endothelium-dependent relaxation. Hogan, M., O'Malley, K.D., Healy, J., O'Brien, S., Bund, S.J. Vascul. Pharmacol. (2005) [Pubmed]
  21. Inhibitors of Na+/H+ exchange block epinephrine- and ADP-induced stimulation of human platelet phospholipase C by blockade of arachidonic acid release at a prior step. Sweatt, J.D., Blair, I.A., Cragoe, E.J., Limbird, L.E. J. Biol. Chem. (1986) [Pubmed]
  22. Role of endothelium-derived prostanoid in angiotensin-induced vasoconstriction. Lin, L., Nasjletti, A. Hypertension (1991) [Pubmed]
  23. Potentiation of norepinephrine-induced contraction by primary prostaglandin receptor activation in rat aorta. Rapoport, R.M. Eur. J. Pharmacol. (1993) [Pubmed]
  24. The interaction of nitric oxide and prostaglandins in the control of corporal smooth muscle tone: evidence for production of a cyclooxygenase-derived endothelium-contracting factor. Minhas, S., Cartledge, J.J., Eardley, I., Joyce, A.D., Morrison, J.F. BJU international. (2001) [Pubmed]
  25. Vascular responses to endothelin-1, angiotensin-II, and U46619 in glycerol-induced acute renal failure. Newaz, M.A., Oyekan, A.O. J. Cardiovasc. Pharmacol. (2001) [Pubmed]
  26. Up-regulation of endothelial cyclooxygenase-2 and prostanoid synthesis by platelets. Role of thromboxane A2. Caughey, G.E., Cleland, L.G., Gamble, J.R., James, M.J. J. Biol. Chem. (2001) [Pubmed]
  27. Thromboxane A(2) receptor mediated activation of the mitogen activated protein kinase cascades in human uterine smooth muscle cells. Miggin, S.M., Kinsella, B.T. Biochim. Biophys. Acta (2001) [Pubmed]
  28. Type 2 diabetic mice have increased arteriolar tone and blood pressure: enhanced release of COX-2-derived constrictor prostaglandins. Bagi, Z., Erdei, N., Toth, A., Li, W., Hintze, T.H., Koller, A., Kaley, G. Arterioscler. Thromb. Vasc. Biol. (2005) [Pubmed]
  29. The promoting effect of epinephrine on lipopolysaccharide-induced interleukin-8 production in whole blood may be mediated by thromboxane A2. Lund, T., Østerud, B. J. Thromb. Haemost. (2003) [Pubmed]
  30. CD40 ligand-dependent tyrosine nitration of prostacyclin synthase in vivo. Davis, B., Zou, M.H. Circulation (2005) [Pubmed]
  31. Thromboxane A2 mediates reperfusion injury after heart preservation. Byrne, J.G., Appleyard, R.F., Sun, S.C., Couper, G.S., Cohn, L.H. J. Heart Lung Transplant. (1993) [Pubmed]
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