Home LiteratureArticle Details
PMID: 16955067 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't Review

NO-independent stimulators and activators of soluble guanylate cyclase: discovery and therapeutic potential.

Nature reviews. Drug discovery ·Vol. 5 ·No. 9 ·2006-09-00 ·Pages 755-68

Evgenov OV, Pacher P, Schmidt PM, Haskó G, Schmidt HH, Stasch JP

Abstract

Soluble guanylate cyclase (sGC) is a key signal-transduction enzyme activated by nitric oxide (NO). Impaired bioavailability and/or responsiveness to endogenous NO has been implicated in the pathogenesis of cardiovascular and other diseases. Current therapies that involve the use of organic nitrates and other NO donors have limitations, including non-specific interactions of NO with various biomolecules, lack of response and the development of tolerance following prolonged administration. Compounds that activate sGC in an NO-independent manner might therefore provide considerable therapeutic advantages. Here we review the discovery, biochemistry, pharmacology and clinical potential of haem-dependent sGC stimulators (including YC-1, BAY 41-2272, BAY 41-8543, CFM-1571 and A-350619) and haem-independent sGC activators (including BAY 58-2667 and HMR-1766).

MeSH Terms
Animals Drug Design Enzyme Activation/drug effects Enzyme Activators/chemistry,pharmacology,therapeutic use Guanylate Cyclase/metabolism Humans Molecular Structure Nitric Oxide/metabolism
Chemicals
Enzyme Activators Nitric Oxide Guanylate Cyclase
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Evgenov Oleg V
Department of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, 55 Fruit Street, CLN 309, Boston, Massachusetts 02114, USA.
Pacher Pál
Schmidt Peter M
Haskó György
Schmidt Harald H H W
Stasch Johannes-Peter
References (151)
151 references, click to expand
  1. Exchange of substrate and inhibitor specificities between adenylyl and guanylyl cyclases.
    J Biol Chem. 1998 Jun 26;273(26):16332-8 PMID: 9632695
  2. Synergistic activation of soluble guanylate cyclase by YC-1 and carbon monoxide: implications for the role of cleavage of the iron-histidine bond during activation by nitric oxide.
    Chem Biol. 1998 May;5(5):255-61 PMID: 9646941
  3. Formation of reactive oxygen species by pentaerithrityltetranitrate and glyceryl trinitrate in vitro and development of nitrate tolerance.
    J Pharmacol Exp Ther. 1998 Aug;286(2):938-44 PMID: 9694953
  4. Alterations of the vascular and the myocardial guanylate cyclase/cGMP-system induced by long-term hypertension in rats.
    Pharm Acta Helv. 1998 Jun;73(1):27-35 PMID: 9708036
  5. The use of nitric oxide donors in pharmacological studies.
    Naunyn Schmiedebergs Arch Pharmacol. 1998 Jul;358(1):113-22 PMID: 9721012
  6. Efficient inhibition of intimal hyperplasia by adenovirus-mediated inducible nitric oxide synthase gene transfer to rats and pigs in vivo.
    J Am Coll Surg. 1998 Sep;187(3):295-306 PMID: 9740187
  7. Human soluble guanylate cyclase: functional expression and revised isoenzyme family.
    Biochem J. 1998 Oct 1;335 ( Pt 1):51-7 PMID: 9742212
  8. Residues stabilizing the heme moiety of the nitric oxide sensor soluble guanylate cyclase.
    Eur J Pharmacol. 2005 Apr 18;513(1-2):67-74 PMID: 15878710
  9. Nitrosative stress and pharmacological modulation of heart failure.
    Trends Pharmacol Sci. 2005 Jun;26(6):302-10 PMID: 15925705
  10. Stimulation of soluble guanylate cyclase slows progression in anti-thy1-induced chronic glomerulosclerosis.
    Kidney Int. 2005 Jul;68(1):47-61 PMID: 15954895
  11. BAY 41-2272 [5-cyclopropyl-2-[1-(2-fluoro-benzyl)-1H-pyrazolo[3,4-b]pyridine-3-yl]pyrimidin-4-ylamine]-induced dilation in ovine pulmonary artery: role of sodium pump.
    J Pharmacol Exp Ther. 2005 Jul;314(1):207-13 PMID: 15792996
  12. Revisiting the kinetics of nitric oxide (NO) binding to soluble guanylate cyclase: the simple NO-binding model is incorrect.
    Proc Natl Acad Sci U S A. 2002 Sep 17;99(19):12097-101 PMID: 12209005
  13. Synaptic localization of nitric oxide synthase and soluble guanylyl cyclase in the hippocampus.
    J Neurosci. 2002 Oct 15;22(20):8961-70 PMID: 12388603
  14. A-350619: a novel activator of soluble guanylyl cyclase.
    Life Sci. 2003 Jan 17;72(9):1015-25 PMID: 12495780
  15. YC-1 potentiates the nitric oxide/cyclic GMP pathway in corpus cavernosum and facilitates penile erection in rats.
    Eur J Pharmacol. 2003 Jan 1;458(1-2):183-9 PMID: 12498924
  16. A stimulatory role for cGMP-dependent protein kinase in platelet activation.
    Cell. 2003 Jan 10;112(1):77-86 PMID: 12526795
  17. The Rho-kinase inhibitor Y-27632 and the soluble guanylyl cyclase activator BAY41-2272 relax rabbit vaginal wall and clitoral corpus cavernosum.
    Br J Pharmacol. 2003 Jan;138(2):287-90 PMID: 12540518
  18. BAY41-2272, a novel nitric oxide independent soluble guanylate cyclase activator, relaxes human and rabbit corpus cavernosum in vitro.
    J Urol. 2003 Feb;169(2):761-6 PMID: 12544359
  19. Cardiorenal and humoral properties of a novel direct soluble guanylate cyclase stimulator BAY 41-2272 in experimental congestive heart failure.
    Circulation. 2003 Feb 11;107(5):686-9 PMID: 12578869
  20. BAY 41-2272: a stimulator of soluble guanylyl cyclase induces nitric oxide-dependent penile erection in vivo.
    Urology. 2003 Feb;61(2):464-7 PMID: 12597982
  21. Mechanisms of nitric oxide independent activation of soluble guanylyl cyclase.
    Eur J Pharmacol. 2003 May 16;468(3):167-74 PMID: 12754054
  22. NO mediates antifibrotic actions of L-arginine supplementation following induction of anti-thy1 glomerulonephritis.
    Kidney Int. 2003 Aug;64(2):509-18 PMID: 12846746
  23. Soluble guanylyl cyclase: physiological role as an NO receptor and the potential molecular target for therapeutic application.
    Clin Chem Lab Med. 2003 Jul;41(7):865-70 PMID: 12940510
  24. YC-1, a novel activator of platelet guanylate cyclase.
    Blood. 1994 Dec 15;84(12):4226-33 PMID: 7527671
  25. Physiology of penile erection.
    Physiol Rev. 1995 Jan;75(1):191-236 PMID: 7831397
  26. Gene therapy inhibiting neointimal vascular lesion: in vivo transfer of endothelial cell nitric oxide synthase gene.
    Proc Natl Acad Sci U S A. 1995 Feb 14;92(4):1137-41 PMID: 7532305
  27. Modulation of nitric oxide-dependent relaxation of pig tracheal smooth muscle by inhibitors of guanylyl cyclase and calcium activated potassium channels.
    Life Sci. 1995;56(25):2229-38 PMID: 7540707
  28. Potent and selective inhibition of nitric oxide-sensitive guanylyl cyclase by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one.
    Mol Pharmacol. 1995 Aug;48(2):184-8 PMID: 7544433
  29. FK409, a new nitric-oxide donor, suppresses smooth muscle proliferation in the rat model of balloon angioplasty.
    Atherosclerosis. 1995 Sep;117(1):97-106 PMID: 8546759
  30. Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms.
    Physiol Rev. 1995 Oct;75(4):725-48 PMID: 7480160
  31. YC-1 inhibited human platelet aggregation through NO-independent activation of soluble guanylate cyclase.
    Br J Pharmacol. 1995 Oct;116(3):1973-8 PMID: 8640334
  32. Specificity of different organic nitrates to elicit NO formation in rabbit vascular tissues and organs in vivo.
    Br J Pharmacol. 1995 Nov;116(6):2743-9 PMID: 8590999
  33. Inhibition of neointimal proliferation in rabbits after vascular injury by a single treatment with a protein adduct of nitric oxide.
    J Clin Invest. 1995 Dec;96(6):2630-8 PMID: 8675628
  34. Characterization of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one as a heme-site inhibitor of nitric oxide-sensitive guanylyl cyclase.
    Mol Pharmacol. 1996 Jul;50(1):1-5 PMID: 8700100
  35. Identification of the enzymatic mechanism of nitroglycerin bioactivation.
    Proc Natl Acad Sci U S A. 2002 Jun 11;99(12):8306-11 PMID: 12048254
  36. Soluble guanylate cyclase: an old therapeutic target re-visited.
    Br J Pharmacol. 2002 Jul;136(5):637-40 PMID: 12086972
  37. NO- and haem-independent activation of soluble guanylyl cyclase: molecular basis and cardiovascular implications of a new pharmacological principle.
    Br J Pharmacol. 2002 Jul;136(5):773-83 PMID: 12086987
  38. Inhibition of deactivation of NO-sensitive guanylyl cyclase accounts for the sensitizing effect of YC-1.
    J Biol Chem. 2002 Jul 12;277(28):24883-8 PMID: 11978784
  39. Antiplatelet properties of a novel, non-NO-based soluble guanylate cyclase activator, BAY 41-2272.
    Vascul Pharmacol. 2003 Oct;40(3):149-54 PMID: 13678646
  40. Relaxing effects induced by the soluble guanylyl cyclase stimulator BAY 41-2272 in human and rabbit corpus cavernosum.
    Eur J Pharmacol. 2003 Sep 12;477(2):163-9 PMID: 14519420
  41. Intravenous sildenafil and inhaled nitric oxide: a randomised trial in infants after cardiac surgery.
    Intensive Care Med. 2003 Nov;29(11):1996-2003 PMID: 14530859
  42. A proatherogenic role for cGMP-dependent protein kinase in vascular smooth muscle cells.
    Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13519-24 PMID: 14597716
  43. Identification of residues crucially involved in the binding of the heme moiety of soluble guanylate cyclase.
    J Biol Chem. 2004 Jan 23;279(4):3025-32 PMID: 14570894
  44. Antiinflammatory activity of soluble guanylate cyclase: cGMP-dependent down-regulation of P-selectin expression and leukocyte recruitment.
    Proc Natl Acad Sci U S A. 2004 Feb 3;101(5):1386-91 PMID: 14742866
  45. Potent inhibition of human platelets by cGMP analogs independent of cGMP-dependent protein kinase.
    Blood. 2004 Apr 1;103(7):2593-600 PMID: 14644996
  46. The inhibitory mechanism of YC-1, a benzyl indazole, on smooth muscle cell proliferation: an in vitro and in vivo study.
    J Pharmacol Sci. 2004 Mar;94(3):252-60 PMID: 15037810
  47. Inhibition of phosphodiesterase type 5 by the activator of nitric oxide-sensitive guanylyl cyclase BAY 41-2272.
    Circulation. 2004 Apr 13;109(14):1711-3 PMID: 15066950
  48. Recent advances in natriuretic peptides in congestive heart failure.
    Expert Opin Investig Drugs. 2004 Jun;13(6):643-52 PMID: 15174950
  49. Inhaled nitric oxide: a selective pulmonary vasodilator: current uses and therapeutic potential.
    Circulation. 2004 Jun 29;109(25):3106-11 PMID: 15226227
  50. Salutary properties of YC-1 in the cardiovascular and hematological systems.
    Curr Med Chem Cardiovasc Hematol Agents. 2004 Oct;2(4):343-59 PMID: 15320784
  51. Nitric oxide and pulmonary arterial pressures in pulmonary hypertension.
    Free Radic Biol Med. 2004 Oct 1;37(7):1010-7 PMID: 15336317
  52. Crystal structure of an oxygen-binding heme domain related to soluble guanylate cyclases.
    Proc Natl Acad Sci U S A. 2004 Aug 31;101(35):12854-9 PMID: 15326296
  53. Effects of the sGC stimulator BAY 41-2272 are not mediated by phosphodiesterase 5 inhibition.
    Circulation. 2004 Sep 21;110(12):e320-1; author reply e320-1 PMID: 15381669
  54. The burden of adult hypertension in the United States 1999 to 2000: a rising tide.
    Hypertension. 2004 Oct;44(4):398-404 PMID: 15326093
  55. Soluble guanylate cyclase activator reverses acute pulmonary hypertension and augments the pulmonary vasodilator response to inhaled nitric oxide in awake lambs.
    Circulation. 2004 Oct 12;110(15):2253-9 PMID: 15466650
  56. Pulmonary arterial hypertension.
    N Engl J Med. 2004 Oct 14;351(16):1655-65 PMID: 15483284
  57. Oral sildenafil is an effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension: comparison with inhaled nitric oxide.
    Circulation. 2002 May 21;105(20):2398-403 PMID: 12021227
  58. A point-mutated guanylyl cyclase with features of the YC-1-stimulated enzyme: implications for the YC-1 binding site?
    Biochemistry. 1999 Nov 16;38(46):15253-7 PMID: 10563809
  59. A molecular basis for nitric oxide sensing by soluble guanylate cyclase.
    Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):14753-8 PMID: 10611285
  60. Aging and chronic hypertension decrease expression of rat aortic soluble guanylyl cyclase.
    Hypertension. 2000 Jan;35(1 Pt 1):43-7 PMID: 10642273
  61. Increased nitrovasodilator sensitivity in endothelial nitric oxide synthase knockout mice: role of soluble guanylyl cyclase.
    Hypertension. 2000 Jan;35(1 Pt 2):231-6 PMID: 10642303
  62. Interaction of soluble guanylate cyclase with YC-1: kinetic and resonance Raman studies.
    Biochemistry. 2000 Apr 11;39(14):4191-8 PMID: 10747811
  63. Acute blood pressure effects of YC-1-induced activation of soluble guanylyl cyclase in normotensive and hypertensive rats.
    Br J Pharmacol. 2000 May;130(2):205-8 PMID: 10807655
  64. Sildenafil is a pulmonary vasodilator in awake lambs with acute pulmonary hypertension.
    Anesthesiology. 2000 Jun;92(6):1702-12 PMID: 10839922
  65. Inhibition of soluble guanylate cyclase by ODQ.
    Biochemistry. 2000 Sep 5;39(35):10848-54 PMID: 10978171
  66. Human recombinant soluble guanylyl cyclase: expression, purification, and regulation.
    Proc Natl Acad Sci U S A. 2000 Sep 26;97(20):10763-8 PMID: 10995472
  67. YC-1, a benzyl indazole derivative, stimulates vascular cGMP and inhibits neointima formation.
    Biochem Biophys Res Commun. 2000 Dec 20;279(2):646-52 PMID: 11118339
  68. Synthesis and biological evaluation of novel pyrazoles and indazoles as activators of the nitric oxide receptor, soluble guanylate cyclase.
    J Med Chem. 2001 Jan 4;44(1):78-93 PMID: 11141091
  69. Soluble guanylate cyclase alpha(1) and beta(1) gene transfer increases NO responsiveness and reduces neointima formation after balloon injury in rats via antiproliferative and antimigratory effects.
    Circ Res. 2001 Jan 19;88(1):103-9 PMID: 11139481
  70. NO-independent regulatory site on soluble guanylate cyclase.
    Nature. 2001 Mar 8;410(6825):212-5 PMID: 11242081
  71. NO-independent stimulators of soluble guanylate cyclase.
    Bioorg Med Chem Lett. 2001 Mar 26;11(6):781-4 PMID: 11277519
  72. Upregulation of vascular NAD(P)H oxidase subunit gp91phox and impairment of the nitric oxide signal transduction pathway in hypertension.
    Biochem Biophys Res Commun. 2001 Aug 3;285(5):1130-5 PMID: 11478771
  73. Pharmacology of penile erection.
    Pharmacol Rev. 2001 Sep;53(3):417-50 PMID: 11546836
  74. Synthesis of 1-benzyl-3-(5'-hydroxymethyl-2'-furyl)indazole analogues as novel antiplatelet agents.
    J Med Chem. 2001 Oct 25;44(22):3746-9 PMID: 11606139
  75. YC-1 activation of human soluble guanylyl cyclase has both heme-dependent and heme-independent components.
    Proc Natl Acad Sci U S A. 2001 Nov 6;98(23):12938-42 PMID: 11687640
  76. cGMP signalling beyond nitric oxide.
    Trends Pharmacol Sci. 2001 Nov;22(11):546-8 PMID: 11698077
  77. Taming platelets with cyclic nucleotides.
    Biochem Pharmacol. 2001 Nov 1;62(9):1153-61 PMID: 11705448
  78. Guanylyl cyclase/PSD-95 interaction: targeting of the nitric oxide-sensitive alpha2beta1 guanylyl cyclase to synaptic membranes.
    J Biol Chem. 2001 Nov 30;276(48):44647-52 PMID: 11572861
  79. Pharmacological actions of a novel NO-independent guanylyl cyclase stimulator, BAY 41-8543: in vitro studies.
    Br J Pharmacol. 2002 Jan;135(2):333-43 PMID: 11815368
  80. Cardiovascular actions of a novel NO-independent guanylyl cyclase stimulator, BAY 41-8543: in vivo studies.
    Br J Pharmacol. 2002 Jan;135(2):344-55 PMID: 11815369
  81. Metabolites of orally active NO-independent pyrazolopyridine stimulators of soluble guanylate cyclase.
    Bioorg Med Chem. 2002 Jun;10(6):1711-7 PMID: 11937330
  82. Calcium-dependent membrane association sensitizes soluble guanylyl cyclase to nitric oxide.
    Nat Cell Biol. 2002 Apr;4(4):307-11 PMID: 11887187
  83. Nitric oxide independent activation of guanylate cyclase by YC-1 causes erectile responses in the rat.
    J Urol. 2002 May;167(5):2276-81 PMID: 11956492
  84. Activation of soluble guanylate cyclase causes relaxation of corpus cavernosum tissue: synergism of nitric oxide and YC-1.
    Int J Impot Res. 2002 Apr;14(2):121-7 PMID: 11979328
  85. A functional heme-binding site of soluble guanylyl cyclase requires intact N-termini of alpha 1 and beta 1 subunits.
    Eur J Biochem. 1996 Sep 1;240(2):380-6 PMID: 8841402
  86. Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction.
    Int J Impot Res. 1996 Jun;8(2):47-52 PMID: 8858389
  87. Characterization of NS 2028 as a specific inhibitor of soluble guanylyl cyclase.
    Br J Pharmacol. 1998 Jan;123(2):299-309 PMID: 9489619
  88. Defective L-arginine-nitric oxide pathway in offspring of essential hypertensive patients.
    Circulation. 1996 Sep 15;94(6):1298-303 PMID: 8822983
  89. YC-1 potentiates nitric oxide- and carbon monoxide-induced cyclic GMP effects in human platelets.
    Mol Pharmacol. 1998 Dec;54(6):962-7 PMID: 9855623
  90. Comparison of two soluble guanylyl cyclase inhibitors, methylene blue and ODQ, on sodium nitroprusside-induced relaxation in guinea-pig trachea.
    Br J Pharmacol. 1998 Nov;125(6):1158-63 PMID: 9863642
  91. Purified soluble guanylyl cyclase expressed in a baculovirus/Sf9 system: stimulation by YC-1, nitric oxide, and carbon monoxide.
    J Mol Med (Berl). 1999 Jan;77(1):14-23 PMID: 9930922
  92. Prevalence and extent of atherosclerosis in adolescents and young adults: implications for prevention from the Pathobiological Determinants of Atherosclerosis in Youth Study.
    JAMA. 1999 Feb 24;281(8):727-35 PMID: 10052443
  93. Effects of the soluble guanylyl cyclase activator, YC-1, on vascular tone, cyclic GMP levels and phosphodiesterase activity.
    Br J Pharmacol. 1999 May;127(1):195-203 PMID: 10369473
  94. Homodimerization of soluble guanylyl cyclase subunits. Dimerization analysis using a glutathione s-transferase affinity tag.
    J Biol Chem. 1999 Jun 25;274(26):18149-52 PMID: 10373411
  95. The soluble guanylyl cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3,-a] quinoxalin-1-one is a nonselective heme protein inhibitor of nitric oxide synthase and other cytochrome P-450 enzymes involved in nitric oxide donor bioactivation.
    Mol Pharmacol. 1999 Aug;56(2):243-53 PMID: 10419542
  96. Downregulation of soluble guanylyl cyclase in young and aging spontaneously hypertensive rats.
    Circ Res. 1999 Sep 17;85(6):534-41 PMID: 10488056
  97. NO activation of guanylyl cyclase.
    EMBO J. 2004 Nov 10;23(22):4443-50 PMID: 15510222
  98. A comparative study of sildenafil, NCX-911 and BAY41-2272 on the anococcygeus muscle of diabetic rats.
    Int J Impot Res. 2004 Dec;16(6):479-85 PMID: 15029225
  99. Reduced cGMP signaling associated with neointimal proliferation and vascular dysfunction in late-stage atherosclerosis.
    Proc Natl Acad Sci U S A. 2004 Nov 23;101(47):16671-6 PMID: 15546990
  100. Femtomolar sensitivity of a NO sensor from Clostridium botulinum.
    Science. 2004 Nov 26;306(5701):1550-3 PMID: 15472039
  101. Expression and activity of soluble guanylate cyclase in injury and repair of anti-thy1 glomerulonephritis.
    Kidney Int. 2004 Dec;66(6):2224-36 PMID: 15569311
  102. Impaired L-arginine transport and endothelial function in hypertensive and genetically predisposed normotensive subjects.
    Circulation. 2004 Dec 14;110(24):3680-6 PMID: 15569830
  103. A heretical view on the role of NO and cGMP in vascular proliferative diseases.
    Trends Mol Med. 2005 Feb;11(2):71-5 PMID: 15694869
  104. Efficacy and optimal dose of sildenafil in primary pulmonary hypertension.
    Int J Cardiol. 2005 Mar 10;99(1):91-5 PMID: 15721505
  105. Stimulation of soluble guanylyl cyclase inhibits mesangial cell proliferation and matrix accumulation in experimental glomerulonephritis.
    Am J Physiol Renal Physiol. 2005 Apr;288(4):F685-93 PMID: 15561976
  106. Expression and characterization of the catalytic domains of soluble guanylate cyclase: interaction with the heme domain.
    Biochemistry. 2005 Mar 15;44(10):4083-90 PMID: 15751985
  107. Effects of BAY 41-2272, a soluble guanylate cyclase activator, on pulmonary vascular reactivity in the ovine fetus.
    Am J Physiol Lung Cell Mol Physiol. 2005 Apr;288(4):L727-33 PMID: 15608146
  108. NO/redox disequilibrium in the failing heart and cardiovascular system.
    J Clin Invest. 2005 Mar;115(3):509-17 PMID: 15765132
  109. A cell-based cGMP assay useful for ultra-high-throughput screening and identification of modulators of the nitric oxide/cGMP pathway.
    Anal Biochem. 2005 Apr 1;339(1):104-12 PMID: 15766716
  110. Inflammation, atherosclerosis, and coronary artery disease.
    N Engl J Med. 2005 Apr 21;352(16):1685-95 PMID: 15843671
  111. Sensitizing soluble guanylyl cyclase to become a highly CO-sensitive enzyme.
    EMBO J. 1996 Dec 16;15(24):6863-8 PMID: 9003762
  112. Functions of conserved cysteines of soluble guanylyl cyclase.
    Biochemistry. 1997 Feb 11;36(6):1194-8 PMID: 9063867
  113. Effect of YC-1, an NO-independent, superoxide-sensitive stimulator of soluble guanylyl cyclase, on smooth muscle responsiveness to nitrovasodilators.
    Br J Pharmacol. 1997 Feb;120(4):681-9 PMID: 9051308
  114. Crystal structure of the catalytic domains of adenylyl cyclase in a complex with Gsalpha.GTPgammaS.
    Science. 1997 Dec 12;278(5345):1907-16 PMID: 9417641
  115. Antiproliferative effects of phosphodiesterase type 5 inhibition in human pulmonary artery cells.
    Am J Respir Crit Care Med. 2005 Jul 1;172(1):105-13 PMID: 15817798
  116. Role of oxidative-nitrosative stress and downstream pathways in various forms of cardiomyopathy and heart failure.
    Curr Vasc Pharmacol. 2005 Jul;3(3):221-9 PMID: 16026319
  117. Ancient conserved domains shared by animal soluble guanylyl cyclases and bacterial signaling proteins.
    BMC Genomics. 2003;4(1):5 PMID: 12590654
  118. Membrane association of nitric oxide-sensitive guanylyl cyclase in cardiomyocytes.
    Cardiovasc Res. 2005 Oct 1;68(1):65-74 PMID: 15953594
  119. Tonic and acute nitric oxide signaling through soluble guanylate cyclase is mediated by nonheme nitric oxide, ATP, and GTP.
    Proc Natl Acad Sci U S A. 2005 Sep 13;102(37):13064-9 PMID: 16131543
  120. ACC/AHA 2005 guideline update for the diagnosis and management of chronic heart failure in the adult: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and Management of Heart Failure).
    J Am Coll Cardiol. 2005 Sep 20;46(6):e1-82 PMID: 16168273
  121. Explaining the phenomenon of nitrate tolerance.
    Circ Res. 2005 Sep 30;97(7):618-28 PMID: 16195486
  122. Pulmonary vascular effects of nitric oxide-cGMP augmentation in a model of chronic pulmonary hypertension in fetal and neonatal sheep.
    Am J Physiol Lung Cell Mol Physiol. 2005 Nov;289(5):L798-806 PMID: 15964898
  123. Enhancing cGMP in experimental progressive renal fibrosis: soluble guanylate cyclase stimulation vs. phosphodiesterase inhibition.
    Am J Physiol Renal Physiol. 2006 Jan;290(1):F167-76 PMID: 16048904
  124. YC-1 [3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole] inhibits neointima formation in balloon-injured rat carotid through suppression of expressions and activities of matrix metalloproteinases 2 and 9.
    J Pharmacol Exp Ther. 2006 Jan;316(1):35-41 PMID: 16183705
  125. Function of cGMP-dependent protein kinases as revealed by gene deletion.
    Physiol Rev. 2006 Jan;86(1):1-23 PMID: 16371594
  126. The design and synthesis of YC-1 analogues as probes for soluble guanylate cyclase.
    Bioorg Med Chem Lett. 2006 Feb1;16(3):618-21 PMID: 16326101
  127. Activation of soluble guanylate cyclase reverses experimental pulmonary hypertension and vascular remodeling.
    Circulation. 2006 Jan 17;113(2):286-95 PMID: 16391154
  128. Antifibrotic agents for liver disease.
    Am J Transplant. 2006 Jan;6(1):12-9 PMID: 16433751
  129. Mitochondrial aldehyde dehydrogenase-2 (ALDH2) Glu504Lys polymorphism contributes to the variation in efficacy of sublingual nitroglycerin.
    J Clin Invest. 2006 Feb;116(2):506-11 PMID: 16440063
  130. Coronary-artery stents.
    N Engl J Med. 2006 Feb 2;354(5):483-95 PMID: 16452560
  131. Disturbances in nitric oxide/cyclic guanosine monophosphate system in SHR/NDmcr-cp rats, a model of metabolic syndrome.
    Life Sci. 2006 Feb 9;78(11):1187-96 PMID: 16188278
  132. Defects in cGMP-PKG pathway contribute to impaired NO-dependent responses in hepatic stellate cells upon activation.
    Am J Physiol Gastrointest Liver Physiol. 2006 Mar;290(3):G535-42 PMID: 16269521
  133. Vasorelaxing effect of BAY 41-2272 in rat basilar artery: involvement of cGMP-dependent and independent mechanisms.
    Hypertension. 2006 Mar;47(3):596-602 PMID: 16391173
  134. Pharmacological management of renal fibrotic disease.
    Expert Opin Pharmacother. 2006 Mar;7(4):377-86 PMID: 16503810
  135. Biochemistry and pharmacology of novel anthranilic acid derivatives activating heme-oxidized soluble guanylyl cyclase.
    Mol Pharmacol. 2006 Apr;69(4):1260-8 PMID: 16332991
  136. Drug discovery technology Europe 2006 - IBC's Tenth Annual Conference and Exhibition.
    IDrugs. 2006 Apr;9(4):256-60 PMID: 16596477
  137. Protective effects of BAY 41-2272 (sGC stimulator) on hypertension, heart, and cardiomyocyte hypertrophy induced by chronic L-NAME treatment in rats.
    J Cardiovasc Pharmacol. 2006 Mar;47(3):391-5 PMID: 16633081
  138. NO-independent activation of soluble guanylate cyclase prevents disease progression in rats with 5/6 nephrectomy.
    Br J Pharmacol. 2006 Jul;148(6):853-9 PMID: 16770325
  139. Functional characterization of two nucleotide-binding sites in soluble guanylate cyclase.
    J Biol Chem. 2006 Aug 4;281(31):21763-70 PMID: 16754683
  140. BAY 41-2272, a direct activator of soluble guanylate cyclase, reduces right ventricular hypertrophy and prevents pulmonary vascular remodeling during chronic hypoxia in neonatal rats.
    Biol Neonate. 2006;90(2):135-44 PMID: 16582538
  141. Targeting the heme-oxidized nitric oxide receptor for selective vasodilatation of diseased blood vessels.
    J Clin Invest. 2006 Sep;116(9):2552-61 PMID: 16955146
  142. Activation of purified soluble guanylate cyclase by protoporphyrin IX.
    Proc Natl Acad Sci U S A. 1982 May;79(9):2870-3 PMID: 6123998
  143. Activation of soluble guanylate cyclase by NO-hemoproteins involves NO-heme exchange. Comparison of heme-containing and heme-deficient enzyme forms.
    J Biol Chem. 1986 Apr 15;261(11):4997-5002 PMID: 2870064
  144. Syndromes of accelerated atherosclerosis: role of vascular injury and smooth muscle cell proliferation.
    J Am Coll Cardiol. 1990 Jun;15(7):1667-87 PMID: 2188991
  145. Nitric oxide and cyclic GMP formation upon electrical field stimulation cause relaxation of corpus cavernosum smooth muscle.
    Biochem Biophys Res Commun. 1990 Jul 31;170(2):843-50 PMID: 2166511
  146. Nitric oxide as a mediator of relaxation of the corpus cavernosum in response to nonadrenergic, noncholinergic neurotransmission.
    N Engl J Med. 1992 Jan 9;326(2):90-4 PMID: 1309211
  147. Effect of increased availability of endothelium-derived nitric oxide precursor on endothelium-dependent vascular relaxation in normal subjects and in patients with essential hypertension.
    Circulation. 1993 May;87(5):1475-81 PMID: 8491002
  148. Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study.
    J Urol. 1994 Jan;151(1):54-61 PMID: 8254833
  149. Novel actions of methylene blue.
    Eur Heart J. 1993 Nov;14 Suppl I:22-6 PMID: 7507438
  150. Mutation of His-105 in the beta 1 subunit yields a nitric oxide-insensitive form of soluble guanylyl cyclase.
    Proc Natl Acad Sci U S A. 1994 Mar 29;91(7):2592-6 PMID: 7908439
  151. NO at work.
    Cell. 1994 Sep 23;78(6):919-25 PMID: 7923361
Article Info
Journal
Nature reviews. Drug discovery
Abbr.
Nat Rev Drug Discov
ISSN
1474-1776
DOI
10.1038/nrd2038
Published
2006-09-00
Pages
755-68
Language
English
Region
England
NLM ID
101124171
PMCID
PMC2225477
Subset
IM
Grants
Intramural NIH HHS · Z01 AA000375-02 · United States
External Links
PubMed source DOI: 10.1038/nrd2038 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2