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Chemical Compound Review

CHEMBL8823     (1S,2R,3S)-1- benzo[1,3]dioxol-5-yl-3-[2...

Synonyms: SureCN1028671, CHEBI:104763, LS-81624, SB-209670, PDSP2_001717, ...
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Disease relevance of SB-209670


High impact information on SB-209670

  • An extremely potent and highly specific non-peptide, subnanomolar endothelin (ET) receptor antagonist, SB 209670, has been synthesized and characterized [5].
  • SB 209670 produces a dose-dependent reduction in blood pressure in hypertensive rats, protects from ischemia-induced neuronal degeneration in a gerbil stroke model, and attenuates neointima formation following rat carotid artery balloon angioplasty [5].
  • This endothelin A receptor-mediated effect was completely inhibited by SB 209670 (IC50, 6.2 +/- 2.2 nmol/L) [6].
  • Administration of an endothelin receptor antagonist (ETRA, SB 209670) to dogs induced damage most frequent and severe in the right coronary artery and right atrium [7].
  • Pharmacokinetics and pharmacodynamics of SB 209670, an endothelin receptor antagonist: effects on the regulation of renal vascular tone [8].

Chemical compound and disease context of SB-209670


Biological context of SB-209670

  • SB 209670 produces concentration-dependent inhibition of ET-1-mediated vasoconstriction in isolated vascular tissues and in vivo following either intravenous or intraduodenal administration [5].
  • Part 1 was a placebo-controlled, single-blind, rising-dose crossover evaluation of the pharmacokinetics and safety of SB 209670 infused at doses that ranged from 0.2 to 1.5 mirog kg(-1) for approximately 8 hours in 17 healthy male volunteers [8].
  • Therefore, the antihypertensive effect of SB 209670 resulted from a decrease (13%) in total peripheral resistance [2].
  • RESULTS: SB 209670 appeared to display linear kinetics over the dose range from 0.2 to 1.5 microg kg(-1) min(-1) [8].
  • Mixed endothelin receptor antagonist, SB209670, decreases portal pressure in biliary cirrhotic rats in vivo by reducing portal venous system resistance [10].

Anatomical context of SB-209670

  • BQ-123 and SB209670 significantly decreased eosinophil number in the bronchoalveolar lavage fluid by 47 and 68%, respectively [11].
  • 2. In rabbit pulmonary artery SB 209670 (10 microM), a mixed ETA/ETB receptor antagonist, was a more potent antagonist of contractions produced by S6c (pKB = 7.7; n = 9; P < 0.05), than those elicited by ET-1 (pKB = 6.7; n = 6) or ET-3 (pKB = 6.7; n = 5) [12].
  • These results suggest that endogenous endothelin plays a role in axonal degeneration after spinal cord injury and that SB209670 prevents or delays the axonal degeneration after CNS damage [13].
  • When SB209670 was administered (30 micro g kg(-1) min(-1) I.V.) for 30 min before, during and for 90 min after renal artery occlusion, cortical and medullary perfusions returned to baseline levels, responses different from those obtained during saline infusion (both P < 0.05) [14].
  • Dose-related increases in the mean percentage of fetuses per litter with malformations were seen at > or = 10 mg/kg/day SB-217242 and > or = 10 mg/kg/day SB-209670 [15].

Associations of SB-209670 with other chemical compounds

  • Affinities of the constrained cyclic pentapeptide BQ-123, the pyrimidinylbenzenesulfonamide bosentan, the indancarboxlic acid SB 209670, and the naphthalenesulfonamide BMS-182874 were decreased 20-1000-fold in Tyr129Ala, Tyr129Ser, and Tyr129His ETA receptor mutants [16].
  • Increases in blood pressure induced by ET-1 (1 pmol; 31 +/- 6.6 mmHg, n = 6) were greatly reduced by pre-administration to the PAG area of FR 139317 (5 nmol per rat) or SB 209670 (3 nmol per rat) (97 and 94%, respectively), but were unaffected by BQ-788 (5 nmol per rat) [17].
  • In contrast, the CGRP1-receptor antagonist, CGRP (8-37), caused small, but significant, inhibitions of the hypotensive and renal and mesenteric vasodilator effects of LPS, but only 6 h after onset of infusion in the presence of dexamethasone and SB 209670 [18].
  • Haemodynamic effects of losartan and the endothelin antagonist, SB 209670, in conscious, transgenic ((mRen-2)27), hypertensive rats [19].
  • The results caused us to reject the hypothesis that selective antagonism of the vasoconstrictor effects of endothelin-1 would result in SB 234551 exerting a greater antihypertensive effect than SB 209670 in TG rats [20].

Gene context of SB-209670


Analytical, diagnostic and therapeutic context of SB-209670

  • Endothelin receptor antagonists such as SB 209670 may therefore serve as useful adjuncts to PTCA, attenuating the degree of vascular restenosis observed after vascular wall injury [6].
  • Intravenous infusion of the ET antagonist SB 209670 at a dose of 30 microg x kg(-1) x min(-1) for 75 minutes caused a significant decrease in MAP in DS rats (from 166+/-3 to 144+/-4 mm Hg) [25].
  • In part 2, renal hemodynamic effects of a 4-hour infusion of SB 209670 were assessed in 10 healthy male volunteers in a 2-period, period-balanced, single-blind, randomized, placebo-controlled crossover study [8].
  • We conclude that treatment of lung allografts with the mixed endothelin A/endothelin B (ETA/ETB) receptor antagonist SB209670 can ameliorate ischemia-reperfusion injury, resulting in improved graft function and survival after lung transplantation [1].
  • METHODS: Eighteen rabbits were divided into three groups: no ischemia followed by 3 hr of reperfusion (group I) and 6 hr of cold ischemia followed by 3 hr of reperfusion with either blood (group II) or blood + SB209670 (mixed ETA/ETB receptor antagonist) (group III) [26].


  1. Efficacy of administering an endothelin-receptor antagonist (SB209670) in ameliorating ischemia-reperfusion injury in lung allografts. Shennib, H., Lee, A.G., Kuang, J.Q., Yanagisawa, M., Ohlstein, E.H., Giaid, A. Am. J. Respir. Crit. Care Med. (1998) [Pubmed]
  2. Antihypertensive actions of the novel nonpeptide endothelin receptor antagonist SB 209670. Douglas, S.A., Gellai, M., Ezekiel, M., Feuerstein, G.Z., Elliott, J.D., Ohlstein, E.H. Hypertension (1995) [Pubmed]
  3. Macrophage and myofibroblast involvement in ischemic acute renal failure is attenuated by endothelin receptor antagonists. Forbes, J.M., Leaker, B., Hewitson, T.D., Becker, G.J., Jones, C.L. Kidney Int. (1999) [Pubmed]
  4. Exacerbation of radiocontrast nephrotoxicity by endothelin receptor antagonism. Wang, A., Holcslaw, T., Bashore, T.M., Freed, M.I., Miller, D., Rudnick, M.R., Szerlip, H., Thames, M.D., Davidson, C.J., Shusterman, N., Schwab, S.J. Kidney Int. (2000) [Pubmed]
  5. SB 209670, a rationally designed potent nonpeptide endothelin receptor antagonist. Ohlstein, E.H., Nambi, P., Douglas, S.A., Edwards, R.M., Gellai, M., Lago, A., Leber, J.D., Cousins, R.D., Gao, A., Frazee, J.S. Proc. Natl. Acad. Sci. U.S.A. (1994) [Pubmed]
  6. A role for endogenous endothelin-1 in neointimal formation after rat carotid artery balloon angioplasty. Protective effects of the novel nonpeptide endothelin receptor antagonist SB 209670. Douglas, S.A., Louden, C., Vickery-Clark, L.M., Storer, B.L., Hart, T., Feuerstein, G.Z., Elliott, J.D., Ohlstein, E.H. Circ. Res. (1994) [Pubmed]
  7. Endothelin receptor subtype distribution predisposes coronary arteries to damage. Louden, C.S., Nambi, P., Pullen, M.A., Thomas, R.A., Tierney, L.A., Solleveld, H.A., Schwartz, L.W. Am. J. Pathol. (2000) [Pubmed]
  8. Pharmacokinetics and pharmacodynamics of SB 209670, an endothelin receptor antagonist: effects on the regulation of renal vascular tone. Freed, M.I., Wilson, D.E., Thompson, K.A., Harris, R.Z., Ilson, B.E., Jorkasky, D.K. Clin. Pharmacol. Ther. (1999) [Pubmed]
  9. Trigeminal nerve ganglion stimulation-induced neurovascular reflexes in the anaesthetized cat: role of endothelin(B) receptors in carotid vasodilatation. Raval, P., Bingham, S., Aiyar, N., Elliott, J.D., Hunter, A.J., Ohlstein, E.H., Parsons, A.A. Br. J. Pharmacol. (1999) [Pubmed]
  10. Mixed endothelin receptor antagonist, SB209670, decreases portal pressure in biliary cirrhotic rats in vivo by reducing portal venous system resistance. Kojima, H., Yamao, J., Tsujimoto, T., Uemura, M., Takaya, A., Fukui, H. J. Hepatol. (2000) [Pubmed]
  11. Endothelin receptor antagonists inhibit antigen-induced lung inflammation in mice. Fujitani, Y., Trifilieff, A., Tsuyuki, S., Coyle, A.J., Bertrand, C. Am. J. Respir. Crit. Care Med. (1997) [Pubmed]
  12. Comparison of endothelin B (ETB) receptors in rabbit isolated pulmonary artery and bronchus. Hay, D.W., Luttmann, M.A., Beck, G., Ohlstein, E.H. Br. J. Pharmacol. (1996) [Pubmed]
  13. SB209670, a potent endothelin receptor antagonist, prevents or delays axonal degeneration after spinal cord injury. Uesugi, M., Kasuya, Y., Hayashi, K., Goto, K. Brain Res. (1998) [Pubmed]
  14. Effect of endothelin antagonists on the renal haemodynamic and tubular responses to ischaemia-reperfusion injury in anaesthetised rats. Ajis, A., Bagnall, N.M., Collis, M.G., Johns, E.J. Exp. Physiol. (2003) [Pubmed]
  15. Developmental toxicity and toxicokinetics of two endothelin receptor antagonists in rats and rabbits. Treinen, K.A., Louden, C., Dennis, M.J., Wier, P.J. Teratology (1999) [Pubmed]
  16. Mutational analysis of the endothelin type A receptor (ETA): interactions and model of selective ETA antagonist BMS-182874 with putative ETA receptor binding cavity. Webb, M.L., Patel, P.S., Rose, P.M., Liu, E.C., Stein, P.D., Barrish, J., Lach, D.A., Stouch, T., Fisher, S.M., Hadjilambris, O., Lee, H., Skwish, S., Dickinson, K.E., Krystek, S.R. Biochemistry (1996) [Pubmed]
  17. Endothelin-1 and the periaqueductal gray area of the rat: an autoradiographic and functional pharmacological study. D'Amico, M., Dashwood, M.R., Warner, T.D. Br. J. Pharmacol. (1996) [Pubmed]
  18. Influence of CGRP (8-37), but not adrenomedullin (22-52), on the haemodynamic responses to lipopolysaccharide in conscious rats. Gardiner, S.M., March, J.E., Kemp, P.A., Bennett, T. Br. J. Pharmacol. (1999) [Pubmed]
  19. Haemodynamic effects of losartan and the endothelin antagonist, SB 209670, in conscious, transgenic ((mRen-2)27), hypertensive rats. Gardiner, S.M., March, J.E., Kemp, P.A., Mullins, J.J., Bennett, T. Br. J. Pharmacol. (1995) [Pubmed]
  20. Cardiovascular effects of endothelin-1 and endothelin antagonists in conscious, hypertensive ((mRen-2)27) rats. Gardiner, S.M., March, J.E., Kemp, P.A., Bennett, T. Br. J. Pharmacol. (2000) [Pubmed]
  21. Effects of the endothelin receptor antagonist, SB 209670, on circulatory failure and organ injury in endotoxic shock in the anaesthetized rat. Ruetten, H., Thiemermann, C., Vane, J.R. Br. J. Pharmacol. (1996) [Pubmed]
  22. Augmented contraction of the human isolated coronary artery by sumatriptan: a possible role for endogenous thromboxane. Maassen VanDenBrink, A., Bax, W.A., Ferrari, M.D., Zijlstra, F.J., Bos, E., Saxena, P.R. Br. J. Pharmacol. (1996) [Pubmed]
  23. Nonpeptide endothelin receptor antagonists. II. Pharmacological characterization of SB 209670. Ohlstein, E.H., Beck, G.R., Douglas, S.A., Nambi, P., Lago, M.A., Gleason, J.G., Ruffolo, R.R., Feuerstein, G., Elliott, J.D. J. Pharmacol. Exp. Ther. (1994) [Pubmed]
  24. Blockade of endothelin receptors reduces diet-induced hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice. Iwasa, S., Fan, J., Miyauchi, T., Watanabe, T. Pathobiology (2001) [Pubmed]
  25. Role of endothelin in mediating the attenuated renal hemodynamics in Dahl salt-sensitive hypertension. Kassab, S., Novak, J., Miller, T., Kirchner, K., Granger, J. Hypertension (1997) [Pubmed]
  26. Endothelin receptor antagonist improves pulmonary hemodynamics during lung ischemia/reperfusion injury. Shennib, H., Kuang, J.Q., Ohlstein, E.H., Giaid, A. Transplantation (1998) [Pubmed]
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