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Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Therapeutic Targeting of the Soluble Guanylate Cyclase

Author(s): Garyfallia I. Makrynitsa, Aikaterini A. Zompra, Aikaterini I. Argyriou, Georgios A. Spyroulias and Stavros Topouzis*

Volume 26, Issue 15, 2019

Page: [2730 - 2747] Pages: 18

DOI: 10.2174/0929867326666190108095851

Price: $65

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Abstract

The soluble guanylate cyclase (sGC) is the physiological sensor for nitric oxide and alterations of its function are actively implicated in a wide variety of pathophysiological conditions. Intense research efforts over the past 20 years have provided significant information on its regulation, culminating in the rational development of approved drugs or investigational lead molecules, which target and interact with sGC through novel mechanisms. However, there are numerous questions that remain unanswered. Ongoing investigations, with the critical aid of structural chemistry studies, try to further elucidate the enzyme’s structural characteristics that define the association of “stimulators” or “activators” of sGC in the presence or absence of the heme moiety, respectively, as well as the precise conformational attributes that will allow the design of more innovative and effective drugs. This review relates the progress achieved, particularly in the past 10 years, in understanding the function of this enzyme, and focusses on a) the rationale and results of its therapeutic targeting in disease situations, depending on the state of enzyme (oxidized or not, heme-carrying or not) and b) the most recent structural studies, which should permit improved design of future therapeutic molecules that aim to directly upregulate the activity of sGC.

Keywords: 6 Soluble guanylate cyclase (sGC), Cyclic guanosine monophosphate (cGMP), Nitric oxide (NO), sGC activators, sGC stimulators, H-NOX domain, heme, Fe.

[1]
Feil, R.; Kemp-Harper, B. cGMP signalling: From bench to bedside. Conference on cGMP generators, effectors and therapeutic implications. EMBO Rep., 2006, 7(2), 149-153.
[http://dx.doi.org/10.1038/sj.embor.7400627] [PMID: 16439998]
[2]
Hobbs, A.J. Soluble guanylate cyclase: An old therapeutic target re-visited. Br. J. Pharmacol., 2002, 136(5), 637-640.
[http://dx.doi.org/10.1038/sj.bjp.0704779] [PMID: 12086972]
[3]
Alderton, W.K.; Cooper, C.E.; Knowles, R.G. Nitric oxide synthases: Structure, function and inhibition. Biochem. J., 2001, 357(Pt 3), 593-615.
[http://dx.doi.org/10.1042/bj3570593] [PMID: 11463332]
[4]
Stuehr, D.J. Structure-function aspects in the nitric oxide synthases. Annu. Rev. Pharmacol. Toxicol., 1997, 37, 339-359.
[http://dx.doi.org/10.1146/annurev.pharmtox.37.1.339] [PMID: 9131257]
[5]
Sanders, K.M.; Ward, S.M. Nitric oxide as a mediator of nonadrenergic noncholinergic neurotransmission. Am. J. Physiol., 1992, 262(3 Pt 1), G379-G392.
[http://dx.doi.org/10.1152/ajpgi.1992.262.3.G379] [PMID: 1347974]
[6]
Erusalimsky, J.D.; Moncada, S. Nitric oxide and mitochondrial signaling: From physiology to pathophysiology. Arterioscler. Thromb. Vasc. Biol., 2007, 27(12), 2524-2531.
[http://dx.doi.org/10.1161/ATVBAHA.107.151167] [PMID: 17885213]
[7]
Lima, B.; Forrester, M.T.; Hess, D.T.; Stamler, J.S. S-nitrosylation in cardiovascular signaling. Circ. Res., 2010, 106(4), 633-646.
[http://dx.doi.org/10.1161/CIRCRESAHA.109.207381] [PMID: 20203313]
[8]
Ashman, D.F.; Lipton, R.; Melicow, M.M.; Price, T.D. Isolation of adenosine 3′, 5′-monophosphate and guanosine 3′, 5′-monophosphate from rat urine. Biochem. Biophys. Res. Commun., 1963, 11, 330-334.
[http://dx.doi.org/10.1016/0006-291X(63)90566-7] [PMID: 13965190]
[9]
Robison, G.A.; Butcher, R.W.; Sutherland, E.W. Cyclic AMP. Annu. Rev. Biochem., 1968, 37, 149-174.
[http://dx.doi.org/10.1146/annurev.bi.37.070168.001053] [PMID: 4299844]
[10]
Hardman, J.G.; Robison, G.A.; Sutherland, E.W. Cyclic nucleotides. Annu. Rev. Physiol., 1971, 33, 311-336.
[http://dx.doi.org/10.1146/annurev.ph.33.030171.001523] [PMID: 4157117]
[11]
Furchgott, R.F.; Zawadzki, J.V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature, 1980, 288(5789), 373-376.
[http://dx.doi.org/10.1038/288373a0] [PMID: 6253831]
[12]
Ignarro, L.J.; Byrns, R.E.; Buga, G.M.; Wood, K.S.; Chaudhuri, G. Pharmacological evidence that endothelium-derived relaxing factor is nitric oxide: Use of pyrogallol and superoxide dismutase to study endothelium-dependent and nitric oxide-elicited vascular smooth muscle relaxation. J. Pharmacol. Exp. Ther., 1988, 244(1), 181-189.
[PMID: 2826766]
[13]
Mittal, C.K.; Arnold, W.P.; Murad, F. Characterization of protein inhibitors of guanylate cyclase activation from rat heart and Bovine lung., Liver, 1978, 37(54.8), 1.5.
[14]
Koesling, D.; Russwurm, M.; Mergia, E.; Mullershausen, F.; Friebe, A. Nitric oxide-sensitive guanylyl cyclase: Structure and regulation. Neurochem. Int., 2004, 45(6), 813-819.
[http://dx.doi.org/10.1016/j.neuint.2004.03.011] [PMID: 15312975]
[15]
Yuen, P.S.; Potter, L.R.; Garbers, D.L. A new form of guanylyl cyclase is preferentially expressed in rat kidney. Biochemistry, 1990, 29(49), 10872-10878.
[http://dx.doi.org/10.1021/bi00501a002] [PMID: 1980215]
[16]
Harteneck, C.; Wedel, B.; Koesling, D.; Malkewitz, J.; Böhme, E.; Schultz, G. Molecular cloning and expression of a new alpha-subunit of soluble guanylyl cyclase. Interchangeability of the alpha-subunits of the enzyme. FEBS Lett., 1991, 292(1-2), 217-222.
[http://dx.doi.org/10.1016/0014-5793(91)80871-Y] [PMID: 1683630]
[17]
Koesling, D. Studying the structure and regulation of soluble guanylyl cyclase. Methods, 1999, 19(4), 485-493.
[http://dx.doi.org/10.1006/meth.1999.0891] [PMID: 10581148]
[18]
Ma, X.; Sayed, N.; Baskaran, P.; Beuve, A.; van den Akker, F. PAS-mediated dimerization of soluble guanylyl cyclase revealed by signal transduction histidine kinase domain crystal structure. J. Biol. Chem., 2008, 283(2), 1167-1178.
[http://dx.doi.org/10.1074/jbc.M706218200] [PMID: 18006497]
[19]
Rothkegel, C.; Schmidt, P.M.; Atkins, D.J.; Hoffmann, L.S.; Schmidt, H.H.; Schröder, H.; Stasch, J.P. Dimerization region of soluble guanylate cyclase characterized by bimolecular fluorescence complementation in vivo. Mol. Pharmacol., 2007, 72(5), 1181-1190.
[http://dx.doi.org/10.1124/mol.107.036368] [PMID: 17715400]
[20]
Underbakke, E.S.; Iavarone, A.T.; Chalmers, M.J.; Pascal, B.D.; Novick, S.; Griffin, P.R.; Marletta, M.A. Nitric oxide-induced conformational changes in soluble guanylate cyclase. Structure, 2014, 22(4), 602-611.
[http://dx.doi.org/10.1016/j.str.2014.01.008] [PMID: 24560804]
[21]
Winger, J.A.; Marletta, M.A. Expression and characterization of the catalytic domains of soluble guanylate cyclase: Interaction with the heme domain. Biochemistry, 2005, 44(10), 4083-4090.
[http://dx.doi.org/10.1021/bi047601d] [PMID: 15751985]
[22]
Gerzer, R.; Böhme, E.; Hofmann, F.; Schultz, G. Soluble guanylate cyclase purified from bovine lung contains heme and copper. FEBS Lett., 1981, 132(1), 71-74.
[http://dx.doi.org/10.1016/0014-5793(81)80429-2] [PMID: 6117479]
[23]
Gerzer, R.; Radany, E.W.; Garbers, D.L. The separation of the heme and apoheme forms of soluble guanylate cyclase. Biochem. Biophys. Res. Commun., 1982, 108(2), 678-686.
[http://dx.doi.org/10.1016/0006-291X(82)90883-X] [PMID: 6128979]
[24]
Humbert, P.; Niroomand, F.; Fischer, G.; Mayer, B.; Koesling, D.; Hinsch, K.D.; Gausepohl, H.; Frank, R.; Schultz, G.; Böhme, E. Purification of soluble guanylyl cyclase from bovine lung by a new immunoaffinity chromatographic method. Eur. J. Biochem., 1990, 190(2), 273-278.
[http://dx.doi.org/10.1111/j.1432-1033.1990.tb15572.x] [PMID: 1973095]
[25]
Tomita, T.; Ogura, T.; Tsuyama, S.; Imai, Y.; Kitagawa, T. Effects of GTP on bound nitric oxide of soluble guanylate cyclase probed by resonance Raman spectroscopy. Biochemistry, 1997, 36(33), 10155-10160.
[http://dx.doi.org/10.1021/bi9710131] [PMID: 9254612]
[26]
Zhao, Y.; Marletta, M.A. Localization of the heme binding region in soluble guanylate cyclase. Biochemistry, 1997, 36(50), 15959-15964.
[http://dx.doi.org/10.1021/bi971825x] [PMID: 9398330]
[27]
Wedel, B.; Humbert, P.; Harteneck, C.; Foerster, J.; Malkewitz, J.; Böhme, E.; Schultz, G.; Koesling, D. Mutation of His-105 in the beta 1 subunit yields a nitric oxide-insensitive form of soluble guanylyl cyclase. Proc. Natl. Acad. Sci. USA, 1994, 91(7), 2592-2596.
[http://dx.doi.org/10.1073/pnas.91.7.2592] [PMID: 7908439]
[28]
Schmidt, P.M.; Schramm, M.; Schröder, H.; Wunder, F.; Stasch, J.P. Identification of residues crucially involved in the binding of the heme moiety of soluble guanylate cyclase. J. Biol. Chem., 2004, 279(4), 3025-3032.
[http://dx.doi.org/10.1074/jbc.M310141200] [PMID: 14570894]
[29]
Schmidt, P.M.; Rothkegel, C.; Wunder, F.; Schröder, H.; Stasch, J.P. Residues stabilizing the heme moiety of the nitric oxide sensor soluble guanylate cyclase. Eur. J. Pharmacol., 2005, 513(1-2), 67-74.
[http://dx.doi.org/10.1016/j.ejphar.2005.02.046] [PMID: 15878710]
[30]
Iyer, L.M.; Anantharaman, V.; Aravind, L. Ancient conserved domains shared by animal soluble guanylyl cyclases and bacterial signaling proteins. BMC Genomics, 2003, 4(1), 5.
[http://dx.doi.org/10.1186/1471-2164-4-5] [PMID: 12590654]
[31]
Karow, D.S.; Pan, D.; Tran, R.; Pellicena, P.; Presley, A.; Mathies, R.A.; Marletta, M.A. Spectroscopic characterization of the soluble guanylate cyclase-like heme domains from Vibrio cholerae and Thermoanaerobacter tengcongensis. Biochemistry, 2004, 43(31), 10203-10211.
[http://dx.doi.org/10.1021/bi049374l] [PMID: 15287748]
[32]
Boon, E.M.; Davis, J.H.; Tran, R.; Karow, D.S.; Huang, S.H.; Pan, D.; Miazgowicz, M.M.; Mathies, R.A.; Marletta, M.A. Nitric oxide binding to prokaryotic homologs of the soluble guanylate cyclase beta1 H-NOX domain. J. Biol. Chem., 2006, 281(31), 21892-21902.
[http://dx.doi.org/10.1074/jbc.M600557200] [PMID: 16728401]
[33]
Pellicena, P.; Karow, D.S.; Boon, E.M.; Marletta, M.A.; Kuriyan, J. Crystal structure of an oxygen-binding heme domain related to soluble guanylate cyclases. Proc. Natl. Acad. Sci. USA, 2004, 101(35), 12854-12859.
[http://dx.doi.org/10.1073/pnas.0405188101] [PMID: 15326296]
[34]
Antoniades, C.; Shirodaria, C.; Crabtree, M.; Rinze, R.; Alp, N.; Cunnington, C.; Diesch, J.; Tousoulis, D.; Stefanadis, C.; Leeson, P.; Ratnatunga, C.; Pillai, R.; Channon, K.M. Altered plasma versus vascular biopterins in human atherosclerosis reveal relationships between endothelial nitric oxide synthase coupling, endothelial function, and inflammation. Circulation, 2007, 116(24), 2851-2859.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.107.704155] [PMID: 18040031]
[35]
Ellulu, M.S.; Patimah, I.; Khaza’ai, H.; Rahmat, A.; Abed, Y.; Ali, F. Atherosclerotic cardiovascular disease: A review of initiators and protective factors. Inflammopharmacology, 2016, 24(1), 1-10.
[http://dx.doi.org/10.1007/s10787-015-0255-y] [PMID: 26750181]
[36]
Papapetropoulos, A.; Hobbs, A.J.; Topouzis, S. Extending the translational potential of targeting NO/cGMP-regulated pathways in the CVS. Br. J. Pharmacol., 2015, 172(6), 1397-1414.
[http://dx.doi.org/10.1111/bph.12980] [PMID: 25302549]
[37]
Stasch, J.P.; Pacher, P.; Evgenov, O.V. Soluble guanylate cyclase as an emerging therapeutic target in cardiopulmonary disease. Circulation, 2011, 123(20), 2263-2273.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.110.981738] [PMID: 21606405]
[38]
Follmann, M.; Griebenow, N.; Hahn, M.G.; Hartung, I.; Mais, F.J.; Mittendorf, J.; Schäfer, M.; Schirok, H.; Stasch, J.P.; Stoll, F.; Straub, A. The chemistry and biology of soluble guanylate cyclase stimulators and activators. Angew. Chem. Int. Ed. Engl., 2013, 52(36), 9442-9462.
[http://dx.doi.org/10.1002/anie.201302588] [PMID: 23963798]
[39]
Buechler, W.A.; Ivanova, K.; Wolfram, G.; Drummer, C.; Heim, J.M.; Gerzer, R. Soluble guanylyl cyclase and platelet function. Ann. N. Y. Acad. Sci., 1994, 714, 151-157.
[http://dx.doi.org/10.1111/j.1749-6632.1994.tb12039.x] [PMID: 7912486]
[40]
Denninger, J.W.; Marletta, M.A. Guanylate cyclase and the. NO/cGMP signaling pathway. Biochim. Biophys. Acta, 1999, 1411(2-3), 334-350.
[http://dx.doi.org/10.1016/S0005-2728(99)00024-9] [PMID: 10320667]
[41]
Warner, T.D.; Mitchell, J.A.; Sheng, H.; Murad, F. Effects of cyclic GMP on smooth muscle relaxation. Adv. Pharmacol., 1994, 26, 171-194.
[http://dx.doi.org/10.1016/S1054-3589(08)60054-X] [PMID: 7913615]
[42]
Behrends, S. Drugs that activate specific nitric oxide sensitive guanylyl cyclase isoforms independent of nitric oxide release. Curr. Med. Chem., 2003, 10(4), 291-301.
[http://dx.doi.org/10.2174/0929867033368286] [PMID: 12570702]
[43]
Evgenov, O.V.; Pacher, P.; Schmidt, P.M.; Haskó, G.; Schmidt, H.H.; Stasch, J.P. NO-independent stimulators and activators of soluble guanylate cyclase: Discovery and therapeutic potential. Nat. Rev. Drug Discov., 2006, 5(9), 755-768.
[http://dx.doi.org/10.1038/nrd2038] [PMID: 16955067]
[44]
Stasch, J.P.; Hobbs, A.J. NO-independent, haem-dependent soluble guanylate cyclase stimulators. Handb. Exp. Pharmacol., 2009, (191), 277-308.
[http://dx.doi.org/10.1007/978-3-540-68964-5_13] [PMID: 19089334]
[45]
Friebe, A.; Schultz, G.; Koesling, D. Sensitizing soluble guanylyl cyclase to become a highly CO-sensitive enzyme. EMBO J., 1996, 15(24), 6863-6868.
[http://dx.doi.org/10.1002/j.1460-2075.1996.tb01078.x] [PMID: 9003762]
[46]
Schmidt, H.H.; Schmidt, P.M.; Stasch, J.P. NO- and haem-independent soluble guanylate cyclase activators. Handb. Exp. Pharmacol., 2009, (191), 309-339.
[http://dx.doi.org/10.1007/978-3-540-68964-5_14] [PMID: 19089335]
[47]
Martin, F.; Baskaran, P.; Ma, X.; Dunten, P.W.; Schaefer, M.; Stasch, J.P.; Beuve, A.; van den Akker, F. Structure of cinaciguat (BAY 58-2667) bound to Nostoc H-NOX domain reveals insights into heme-mimetic activation of the soluble guanylyl cyclase. J. Biol. Chem., 2010, 285(29), 22651-22657.
[http://dx.doi.org/10.1074/jbc.M110.111559] [PMID: 20463019]
[48]
Evgenov, O.V.; Pacher, P.; Schmidt, P.M.; Haskó, G.; Schmidt, H.H.; Stasch, J-P. NO-independent stimulators and activators of soluble guanylate cyclase: discovery and therapeutic potential. Nat. Rev. Drug Discov., 2006, 5(9), 755-768.
[http://dx.doi.org/10.1038/nrd2038] [PMID: 16955067]
[49]
Sayed, N.; Kim, D.D.; Fioramonti, X.; Iwahashi, T.; Durán, W.N.; Beuve, A. Nitroglycerin-induced S-nitrosylation and desensitization of soluble guanylyl cyclase contribute to nitrate tolerance. Circ. Res., 2008, 103(6), 606-614.
[http://dx.doi.org/10.1161/CIRCRESAHA.108.175133] [PMID: 18669924]
[50]
Stasch, J-P.; Schmidt, P.M.; Nedvetsky, P.I.; Nedvetskaya, T.Y. H s, A.K.; Meurer, S.; Deile, M.; Taye, A.; Knorr, A.; Lapp, H.; Müller, H.; Turgay, Y.; Rothkegel, C.; Tersteegen, A.; Kemp-Harper, B.; Müller-Esterl, W.; Schmidt, H.H. Targeting the heme-oxidized nitric oxide receptor for selective vasodilatation of diseased blood vessels. J. Clin. Invest., 2006, 116(9), 2552-2561.
[http://dx.doi.org/10.1172/JCI28371] [PMID: 16955146]
[51]
Stasch, J.; Hobbs, A.J. NO-independent, haem-dependent soluble guanylate cyclase stimulators. Handb. Exp. Pharmacol., 2009, 277-308.
[http://dx.doi.org/10.1007/978-3-540-68964-5_13]
[52]
Stasch, J.P.; Evgenov, O.V. Soluble guanylate cyclase stimulators in pulmonary hypertension. Pharmacother. Pulmon. Hyperten., 2013, 218, 279-313.
[http://dx.doi.org/10.1007/978-3-662-45805-1_12] [PMID: 24092345]
[53]
Ghofrani, H.A.; D’Armini, A.M.; Grimminger, F.; Hoeper, M.M.; Jansa, P.; Kim, N.H.; Mayer, E.; Simonneau, G.; Wilkins, M.R.; Fritsch, A.; Neuser, D.; Weimann, G.; Wang, C. Riociguat for the treatment of chronic thromboembolic pulmonary hypertension. N. Engl. J. Med., 2013, 369(4), 319-329.
[http://dx.doi.org/10.1056/NEJMoa1209657] [PMID: 23883377]
[54]
Ghofrani, H.A.; Galiè, N.; Grimminger, F.; Grünig, E.; Humbert, M.; Jing, Z.C.; Keogh, A.M.; Langleben, D.; Kilama, M.O.; Fritsch, A.; Neuser, D.; Rubin, L.J. Riociguat for the treatment of pulmonary arterial hypertension. N. Engl. J. Med., 2013, 369(4), 330-340.
[http://dx.doi.org/10.1056/NEJMoa1209655] [PMID: 23883378]
[55]
Schermuly, R.T.; Stasch, J-P.; Pullamsetti, S.S.; Middendorff, R.; Müller, D.; Schlüter, K-D.; Dingendorf, A.; Hackemack, S.; Kolosionek, E.; Kaulen, C.; Dumitrascu, R.; Weissmann, N.; Mittendorf, J.; Klepetko, W.; Seeger, W.; Ghofrani, H.A.; Grimminger, F. Expression and function of soluble guanylate cyclase in pulmonary arterial hypertension. Eur. Respir. J., 2008, 32(4), 881-891.
[http://dx.doi.org/10.1183/09031936.00114407] [PMID: 18550612]
[56]
Stasch, J.P.; Pacher, P.; Evgenov, O.V. Soluble guanylate cyclase as an emerging therapeutic target in cardiopulmonary disease. Circulation, 2011, 123(20), 2263-2273.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.110.981738] [PMID: 21606405]
[57]
Lang, M.; Kojonazarov, B.; Tian, X.; Kalymbetov, A.; Weissmann, N.; Grimminger, F.; Kretschmer, A.; Stasch, J-P.; Seeger, W.; Ghofrani, H.A.; Schermuly, R.T. The soluble guanylate cyclase stimulator riociguat ameliorates pulmonary hypertension induced by hypoxia and SU5416 in rats. PLoS One, 2012, 7(8)e43433
[http://dx.doi.org/10.1371/journal.pone.0043433] [PMID: 22912874]
[58]
Halank, M.; Hoeper, M.M.; Ghofrani, H-A.; Meyer, F.J.; Stähler, G.; Behr, J.; Ewert, R.; Fletcher, M.; Colorado, P.; Nikkho, S.; Grimminger, F. Riociguat for pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension: Results from a phase II long-term extension study. Respir. Med., 2017, 128, 50-56.
[http://dx.doi.org/10.1016/j.rmed.2017.05.008] [PMID: 28610669]
[59]
Benza, R.; Mathai, S.; Nathan, S.D. sGC stimulators: Evidence for riociguat beyond groups 1 and 4 pulmonary hypertension. Respir. Med., 2017, 122(Suppl. 1), S28-S34.
[http://dx.doi.org/10.1016/j.rmed.2016.11.010] [PMID: 27890470]
[60]
Huntgeburth, M.; Kießling, J.; Weimann, G.; Kiepsel, V.; Saleh, S.; Hunzelmann, N.; Rosenkranz, S. The sGC-stimulator Riociguat for the treatment of Raynaud’s phenomenon: A single-dose, double-blind, randomized, placebo-controlled cross-over study (DIGIT). BMC Pharmacol. Toxicol., 2015, 16(1), A58.
[http://dx.doi.org/10.1186/2050-6511-16-S1-A58]
[61]
Follmann, M.; Ackerstaff, J.; Redlich, G.; Wunder, F.; Lang, D.; Kern, A.; Fey, P.; Griebenow, N.; Kroh, W.; Becker-Pelster, E.M.; Kretschmer, A.; Geiss, V.; Li, V.; Straub, A.; Mittendorf, J.; Jautelat, R.; Schirok, H.; Schlemmer, K.H.; Lustig, K.; Gerisch, M.; Knorr, A.; Tinel, H.; Mondritzki, T.; Trübel, H.; Sandner, P.; Stasch, J.P. Discovery of the soluble guanylate cyclase stimulator vericiguat (bay 1021189) for the treatment of chronic heart failure. J. Med. Chem., 2017, 60(12), 5146-5161.
[http://dx.doi.org/10.1021/acs.jmedchem.7b00449] [PMID: 28557445]
[62]
Pieske, B.; Maggioni, A.P.; Lam, C.S.P.; Pieske-Kraigher, E.; Filippatos, G.; Butler, J.; Ponikowski, P.; Shah, S.J.; Solomon, S.D.; Scalise, A.V.; Mueller, K.; Roessig, L.; Gheorghiade, M. Vericiguat in patients with worsening chronic heart failure and preserved ejection fraction: Results of the soluble guanylate cyclase stimulator in heart failure patients with preserved EF (socrates-preserved) study. Eur. Heart J., 2017, 38(15), 1119-1127.
[http://dx.doi.org/10.1093/eurheartj/ehw593] [PMID: 28369340]
[63]
Filippatos, G.; Maggioni, A.P.; Lam, C.S.P.; Pieske-Kraigher, E.; Butler, J.; Spertus, J.; Ponikowski, P.; Shah, S.J.; Solomon, S.D.; Scalise, A.V.; Mueller, K.; Roessig, L.; Bamber, L.; Gheorghiade, M.; Pieske, B. Patient-reported outcomes in the soluble guanylate cyclase stimulator in heart failure patients with preserved ejection fraction (socrates-preserved) study. Eur. J. Heart Fail., 2017, 19(6), 782-791.
[http://dx.doi.org/10.1002/ejhf.800] [PMID: 28586537]
[64]
Gheorghiade, M.; Greene, S.J.; Butler, J.; Filippatos, G.; Lam, C.S.; Maggioni, A.P.; Ponikowski, P.; Shah, S.J.; Solomon, S.D.; Kraigher-Krainer, E.; Samano, E.T.; Müller, K.; Roessig, L.; Pieske, B. Effect of vericiguat, a soluble guanylate cyclase stimulator, on natriuretic peptide levels in patients with worsening chronic heart failure and reduced ejection fraction: The socrates-reduced randomized trial. JAMA, 2015, 314(21), 2251-2262.
[http://dx.doi.org/10.1001/jama.2015.15734] [PMID: 26547357]
[65]
Pieske, B.; Butler, J.; Filippatos, G.; Lam, C.; Maggioni, A.P.; Ponikowski, P.; Shah, S.; Solomon, S.; Kraigher-Krainer, E.; Samano, E.T.; Scalise, A.V.; Müller, K.; Roessig, L.; Gheorghiade, M. Rationale and design of the soluble guanylate cyclase stimulator in heart failure studies (socrates). Eur. J. Heart Fail., 2014, 16(9), 1026-1038.
[http://dx.doi.org/10.1002/ejhf.135] [PMID: 25056511]
[66]
Armstrong, P.W.; Roessig, L.; Patel, M.J.; Anstrom, K.J.; Butler, J.; Voors, A.A.; Lam, C.S.; Ponikowski, P.; Temple, T.; Pieske, B.; Multicenter, A. Randomized, double-blind, placebo-controlled trial of the efficacy and safety of the oral soluble guanylate cyclase stimulator: The victoria trial. JACC Heart Fail., 2017.
[http://dx.doi.org/ 10.1016/j.jchf.2017.08.013] [PMID: 29032136]
[67]
Gheorghiade, M.; Greene, S.J.; Filippatos, G.; Erdmann, E.; Ferrari, R.; Levy, P.D.; Maggioni, A.; Nowack, C.; Mebazaa, A. Cinaciguat, a soluble guanylate cyclase activator: Results from the randomized, controlled, phase IIb COMPOSE programme in acute heart failure syndromes. Eur. J. Heart Fail., 2012, 14(9), 1056-1066.
[http://dx.doi.org/10.1093/eurjhf/hfs093] [PMID: 22713287]
[68]
Erdmann, E.; Semigran, M.J.; Nieminen, M.S.; Gheorghiade, M.; Agrawal, R.; Mitrovic, V.; Mebazaa, A. Cinaciguat, a soluble guanylate cyclase activator, unloads the heart but also causes hypotension in acute decompensated heart failure. Eur. Heart J., 2013, 34(1), 57-67.
[http://dx.doi.org/10.1093/eurheartj/ehs196] [PMID: 22778174]
[69]
Stasch, J.P.; Schlossmann, J.; Hocher, B. Renal effects of soluble guanylate cyclase stimulators and activators: A review of the preclinical evidence. Curr. Opin. Pharmacol., 2015, 21, 95-104.
[http://dx.doi.org/10.1016/j.coph.2014.12.014] [PMID: 25645316]
[70]
Kumar, V.; Martin, F.; Hahn, M.G.; Schaefer, M.; Stamler, J.S.; Stasch, J.P.; van den Akker, F. Insights into BAY 60-2770 activation and S-nitrosylation-dependent desensitization of soluble guanylyl cyclase via crystal structures of homologous nostoc H-NOX domain complexes. Biochemistry, 2013, 52(20), 3601-3608.
[http://dx.doi.org/10.1021/bi301657w] [PMID: 23614626]
[71]
Rekowski, M.V.W.; Kumar, V.; Zhou, Z.; Moschner, J.; Marazioti, A.; Bantzi, M.; Spyroulias, G.A.; van den Akker, F.; Giannis, A.; Papapetropoulos, A. Insights into soluble guanylyl cyclase activation derived from improved heme-mimetics. J. Med. Chem., 2013, 56(21), 8948-8952.
[http://dx.doi.org/10.1021/jm400539d] [PMID: 24090476]
[72]
Martin, F.; Baskaran, P.; Ma, X.; Dunten, P.W.; Schaefer, M.; Stasch, J.P.; Beuve, A.; van den Akker, F. Structure of cinaciguat (BAY 58-2667) bound to Nostoc H-NOX domain reveals insights into heme-mimetic activation of the soluble guanylyl cyclase. J. Biol. Chem., 2010, 285(29), 22651-22657.
[http://dx.doi.org/10.1074/jbc.M110.111559] [PMID: 20463019]
[73]
Ma, X. Sayed, N.; Beuve, A.; van den Akker, F. NO and CO differentially activate soluble guanylyl cyclase via a heme pivot-bend mechanism. EMBO J., 2007, 26(2), 578-588.
[http://dx.doi.org/10.1038/sj.emboj.7601521] [PMID: 17215864]
[74]
Hespen, C.W.; Bruegger, J.J.; Phillips-Piro, C.M.; Marletta, M.A. Bruegger, J. J.; Phillips-Piro, C. M.; Marletta, M. A., Structural and functional evidence indicates selective oxygen signaling in Caldanaerobacter subterraneus H-NOX. ACS Chem. Biol., 2016, 11(8), 2337-2346.
[http://dx.doi.org/10.1021/acschembio.6b00431] [PMID: 27328180]
[75]
Herzik, M.A., Jr; Jonnalagadda, R.; Kuriyan, J.; Marletta, M.A. Structural insights into the role of iron-histidine bond cleavage in nitric oxide-induced activation of H-NOX gas sensor proteins. Proc. Natl. Acad. Sci. USA, 2014, 111(40), E4156-E4164.
[http://dx.doi.org/10.1073/pnas.1416936111] [PMID: 25253889]
[76]
Alexandropoulos, I.I.; Argyriou, A.I.; Marousis, K.D.; Topouzis, S.; Papapetropoulos, A.; Spyroulias, G.A. (1)H, (13)C, (15)N backbone and side-chain resonance assignment of Nostoc sp. C139A variant of the heme-nitric oxide/oxygen binding (H-NOX) domain. Biomol. NMR Assign., 2016, 10(2), 395-400.
[http://dx.doi.org/10.1007/s12104-016-9707-6] [PMID: 27614467]
[77]
Mülsch, A.; Bauersachs, J.; Schäfer, A.; Stasch, J.P.; Kast, R.; Busse, R. Effect of YC-1, an NO-independent, superoxide-sensitive stimulator of soluble guanylyl cyclase, on smooth muscle responsiveness to nitrovasodilators. Br. J. Pharmacol., 1997, 120(4), 681-689.
[http://dx.doi.org/10.1038/sj.bjp.0700982] [PMID: 9051308]
[78]
Stasch, J.P.; Becker, E.M.; Alonso-Alija, C.; Apeler, H.; Dembowsky, K.; Feurer, A.; Gerzer, R.; Minuth, T.; Perzborn, E.; Pleiss, U.; Schröder, H.; Schroeder, W.; Stahl, E.; Steinke, W.; Straub, A.; Schramm, M. NO-independent regulatory site on soluble guanylate cyclase. Nature, 2001, 410(6825), 212-215.
[http://dx.doi.org/10.1038/35065611] [PMID: 11242081]
[79]
Ko, F.N.; Wu, C.C.; Kuo, S.C.; Lee, F.Y.; Teng, C.M. YC-1, a novel activator of platelet guanylate cyclase. Blood, 1994, 84(12), 4226-4233.
[PMID: 7527671]
[80]
Straub, A.; Stasch, J.P.; Alonso-Alija, C.; Benet-Buchholz, J.; Ducke, B.; Feurer, A.; Fürstner, C. NO-independent stimulators of soluble guanylate cyclase. Bioorg. Med. Chem. Lett., 2001, 11(6), 781-784.
[http://dx.doi.org/10.1016/S0960-894X(01)00073-7] [PMID: 11277519]
[81]
Mittendorf, J.; Weigand, S.; Alonso-Alija, C.; Bischoff, E.; Feurer, A.; Gerisch, M.; Kern, A.; Knorr, A.; Lang, D.; Muenter, K.; Radtke, M.; Schirok, H.; Schlemmer, K.H.; Stahl, E.; Straub, A.; Wunder, F.; Stasch, J.P. Discovery of riociguat (BAY 63-2521): A potent, oral stimulator of soluble guanylate cyclase for the treatment of pulmonary hypertension. ChemMedChem, 2009, 4(5), 853-865.
[http://dx.doi.org/10.1002/cmdc.200900014] [PMID: 19263460]
[82]
Frey, R.; Mück, W.; Unger, S.; Artmeier-Brandt, U.; Weimann, G.; Wensing, G. Single-dose pharmacokinetics, pharmacodynamics, tolerability, and safety of the soluble guanylate cyclase stimulator BAY 63-2521: An ascending-dose study in healthy male volunteers. J. Clin. Pharmacol., 2008, 48(8), 926-934.
[http://dx.doi.org/10.1177/0091270008319793] [PMID: 18519919]
[83]
Shah, P.; Westwell, A.D. The role of fluorine in medicinal chemistry. J. Enzyme Inhib. Med. Chem., 2007, 22(5), 527-540.
[http://dx.doi.org/10.1080/14756360701425014] [PMID: 18035820]
[84]
Selwood, D.L.; Brummell, D.G.; Budworth, J.; Burtin, G.E.; Campbell, R.O.; Chana, S.S.; Charles, I.G.; Fernandez, P.A.; Glen, R.C.; Goggin, M.C.; Hobbs, A.J.; Kling, M.R.; Liu, Q.; Madge, D.J.; Meillerais, S.; Powell, K.L.; Reynolds, K.; Spacey, G.D.; Stables, J.N.; Tatlock, M.A.; Wheeler, K.A.; Wishart, G.; Woo, C.K. Synthesis and biological evaluation of novel pyrazoles and indazoles as activators of the nitric oxide receptor, soluble guanylate cyclase. J. Med. Chem., 2001, 44(1), 78-93.
[http://dx.doi.org/10.1021/jm001034k] [PMID: 11141091]
[85]
Nakai, T.; Perl, N.R.; Barden, T.C.; Carvalho, A.; Fretzen, A.; Germano, P. Im, G.Y.; Jin, H.; Kim, C.; Lee, T.W.; Long, K.; Moore, J.; Rohde, J.M.; Sarno, R.; Segal, C.; Solberg, E.O.; Tobin, J.; Zimmer, D.P.; Currie, M.G. Discovery of IWP-051, a novel orally bioavailable sGC stimulator with once-daily dosing potential in humans. ACS Med. Chem. Lett., 2016, 7(5), 465-469.
[http://dx.doi.org/10.1021/acsmedchemlett.5b00479] [PMID: 27190594]
[86]
Nakane, M.; Kolasa, T.; Chang, R.; Miller, L.N.; Moreland, R.B.; Brioni, J.D. Acrylamide analog as a novel nitric oxide-independent soluble guanylyl cyclase activator. J. Pharmacol. Sci., 2006, 102(2), 231-238.
[http://dx.doi.org/10.1254/jphs.FPJ06017X] [PMID: 17050951]
[87]
Lamothe, M.; Chang, F-J.; Balashova, N.; Shirokov, R.; Beuve, A. Functional characterization of nitric oxide and YC-1 activation of soluble guanylyl cyclase: Structural implication for the YC-1 binding site? Biochemistry, 2004, 43(11), 3039-3048.
[http://dx.doi.org/10.1021/bi0360051] [PMID: 15023055]
[88]
Yazawa, S.; Tsuchiya, H.; Hori, H.; Makino, R. Functional characterization of two nucleotide-binding sites in soluble guanylate cyclase. J. Biol. Chem., 2006, 281(31), 21763-21770.
[http://dx.doi.org/10.1074/jbc.M508983200] [PMID: 16754683]
[89]
Hu, X.; Murata, L.B.; Weichsel, A.; Brailey, J.L.; Roberts, S.A.; Nighorn, A.; Montfort, W.R. Allostery in recombinant soluble guanylyl cyclase from Manduca sexta. J. Biol. Chem., 2008, 283(30), 20968-20977.
[http://dx.doi.org/10.1074/jbc.M801501200] [PMID: 18515359]
[90]
Ibrahim, M.; Derbyshire, E.R.; Marletta, M.A.; Spiro, T.G. Probing soluble guanylate cyclase activation by CO and YC-1 using resonance Raman spectroscopy. Biochemistry, 2010, 49(18), 3815-3823.
[http://dx.doi.org/10.1021/bi902214j] [PMID: 20353168]
[91]
Ibrahim, M.; Derbyshire, E.R.; Soldatova, A.V.; Marletta, M.A.; Spiro, T.G. Soluble guanylate cyclase is activated differently by excess NO and by YC-1: Resonance raman spectroscopic evidence. Biochemistry, 2010, 49(23), 4864-4871.
[http://dx.doi.org/10.1021/bi100506j] [PMID: 20459051]
[92]
Martin, E.; Czarnecki, K.; Jayaraman, V.; Murad, F.; Kincaid, J. Resonance raman and infrared spectroscopic studies of high-output forms of human soluble guanylyl cyclase. J. Am. Chem. Soc., 2005, 127(13), 4625-4631.
[http://dx.doi.org/10.1021/ja0440912] [PMID: 15796527]
[93]
Yoo, B.K.; Lamarre, I.; Rappaport, F.; Nioche, P.; Raman, C.S.; Martin, J.L.; Negrerie, M. Picosecond to second dynamics reveals a structural transition in Clostridium botulinum NO-sensor triggered by the activator BAY-41-2272. ACS Chem. Biol., 2012, 7(12), 2046-2054.
[http://dx.doi.org/10.1021/cb3003539] [PMID: 23009307]
[94]
Stasch, J.P.; Schmidt, P.; Alonso-Alija, C.; Apeler, H.; Dembowsky, K.; Haerter, M.; Heil, M.; Minuth, T.; Perzborn, E.; Pleiss, U.; Schramm, M.; Schroeder, W.; Schröder, H.; Stahl, E.; Steinke, W.; Wunder, F. NO- and haem-independent activation of soluble guanylyl cyclase: Molecular basis and cardiovascular implications of a new pharmacological principle. Br. J. Pharmacol., 2002, 136(5), 773-783.
[http://dx.doi.org/10.1038/sj.bjp.0704778] [PMID: 12086987]
[95]
Schmidt, P.; Schramm, M.; Schröder, H.; Stasch, J.P. Mechanisms of nitric oxide independent activation of soluble guanylyl cyclase. Eur. J. Pharmacol., 2003, 468(3), 167-174.
[http://dx.doi.org/10.1016/S0014-2999(03)01674-1] [PMID: 12754054]
[96]
Sharina, I.G.; Sobolevsky, M.; Papakyriakou, A.; Rukoyatkina, N.; Spyroulias, G.A.; Gambaryan, S.; Martin, E. The fibrate gemfibrozil is a NO- and haem-independent activator of soluble guanylyl cyclase: in vitro studies. Br. J. Pharmacol., 2015, 172(9), 2316-2329.
[http://dx.doi.org/10.1111/bph.13055] [PMID: 25536881]
[97]
Sömmer, A.; Sandner, P.; Behrends, S. BAY 60-2770 activates two isoforms of nitric oxide sensitive guanylyl cyclase: Evidence for stable insertion of activator drugs. Biochem. Pharmacol., 2017.
[PMID: 29155144]
[98]
Kollau, A.; Opelt, M.; Wölkart, G.; Gorren, A.C.; Russwurm, M.; Koesling, D.; Mayer, B.; Schrammel, A. Irreversible activation and stabilization of soluble guanylate cyclase by the protoporphyrin IX mimetic cinaciguat. Mol. Pharmacol., 2018, 93(2), 73-78.
[http://dx.doi.org/10.1124/mol.117.109918] [PMID: 29138269]
[99]
Winter, M.B.; Herzik, M.A., Jr; Kuriyan, J.; Marletta, M.A. Tunnels modulate ligand flux in a heme nitric oxide/oxygen binding (H-NOX) domain. Proc. Natl. Acad. Sci. USA, 2011, 108(43), E881-E889.
[http://dx.doi.org/10.1073/pnas.1114038108] [PMID: 21997213]
[100]
Weinert, E.E.; Phillips-Piro, C.M.; Tran, R.; Mathies, R.A.; Marletta, M.A. Controlling conformational flexibility of an O2-binding H-NOX domain. Biochemistry, 2011, 50(32), 6832-6840.
[http://dx.doi.org/10.1021/bi200788x] [PMID: 21721586]
[101]
Weinert, E.E.; Plate, L.; Whited, C.A.; Olea, C., Jr; Marletta, M.A. Determinants of ligand affinity and heme reactivity in H-NOX domains. Angew. Chem. Int. Ed. Engl., 2010, 49(4), 720-723.
[http://dx.doi.org/10.1002/anie.200904799] [PMID: 20017169]
[102]
Olea, C., Jr; Boon, E.M.; Pellicena, P.; Kuriyan, J.; Marletta, M.A. Probing the function of heme distortion in the H-NOX family. ACS Chem. Biol., 2008, 3(11), 703-710.
[http://dx.doi.org/10.1021/cb800185h] [PMID: 19032091]
[103]
Erbil, W.K.; Price, M.S.; Wemmer, D.E.; Marletta, M.A. A structural basis for H-NOX signaling in Shewanella oneidensis by trapping a histidine kinase inhibitory conformation. Proc. Natl. Acad. Sci. USA, 2009, 106(47), 19753-19760.
[http://dx.doi.org/10.1073/pnas.0911645106] [PMID: 19918063]

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