@article{uoadl:3060897,
    volume = "172",
    number = "6",
    pages = "1397-1414",
    journal = "British Journal of Pharmacology",
    issn = "0007-1188, 1476-5381",
    keywords = "4 amino 5 cyclopropyl 2 [1 (2 fluorobenzyl) 1h pyrazolo[3,4 b]pyridin 3 yl]pyrimidine;  acetylsalicylic acid 3 (nitroxymethyl)phenyl ester;  antiinflammatory agent;  ataciguat;  cinaciguat;  cyclic GMP;  cyclic GMP dependent protein kinase 1;  endothelial nitric oxide synthase;  gsk 2181236a;  guanylate cyclase;  guanylate cyclase activator;  inducible nitric oxide synthase;  inorganic nitrite;  lificiguat;  naproxcinod;  ncx 1015;  neuronal nitric oxide synthase;  nitrate;  nitric oxide;  nitric oxide donating antiinflammatory agent;  nitric oxide synthase inhibitor;  nitrite;  phosphodiesterase III;  phosphodiesterase V;  riociguat;  sildenafil;  soluble guanylate cyclase;  soluble guanylate cyclase stimulator;  tadalafil;  unclassified drug;  unindexed drug;  cell receptor;  cyclic GMP;  guanylate cyclase;  nitric oxide;  soluble guanylyl cyclase, acute heart failure;  acute heart infarction;  Becker muscular dystrophy;  biosynthesis;  brain edema;  brown adipose tissue;  cardiovascular system;  catalysis;  chronic thromboembolic pulmonary hypertension;  combination chemotherapy;  conformational transition;  diabetic cardiomyopathy;  drug indication;  drug mechanism;  drug targeting;  energy expenditure;  enzymatic degradation;  enzyme activity;  enzyme binding;  enzyme inhibition;  heart failure;  human;  hypertension;  lung fibrosis;  metabolic regulation;  molecular dynamics;  monotherapy;  nonhuman;  outcome assessment;  oxidation reduction state;  oxidative stress;  peripheral occlusive artery disease;  phenotype;  priority journal;  protein expression;  pulmonary hypertension;  Raynaud phenomenon;  reperfusion injury;  Review;  sepsis;  signal transduction;  structure activity relation;  systolic heart failure;  translational research;  upregulation;  white adipose tissue;  animal;  Cardiovascular Diseases;  cardiovascular system;  drug design;  metabolism;  molecularly targeted therapy;  pathophysiology;  physiology, Animals;  Cardiovascular Diseases;  Cardiovascular System;  Cyclic GMP;  Drug Design;  Guanylate Cyclase;  Humans;  Molecular Targeted Therapy;  Nitric Oxide;  Receptors, Cytoplasmic and Nuclear;  Signal Transduction",
    BIBTEX_ENTRY = "article",
    year = "2015",
    author = "Papapetropoulos, A. and Hobbs, A.J. and Topouzis, S.",
    abstract = "The discovery of NO as both an endogenous signalling molecule and as a mediator of the cardiovascular effects of organic nitrates was acknowledged in 1998 by the Nobel Prize in Physiology/Medicine. The characterization of its downstream signalling, mediated through stimulation of soluble GC (sGC) and cGMP generation, initiated significant translational interest, but until recently this was almost exclusively embodied by the use of PDE5 inhibitors in erectile dysfunction. Since then, research progress in two areas has contributed to an impressive expansion of the therapeutic targeting of the NO-sGC-cGMP axis: first, an increased understanding of the molecular events operating within this complex pathway and second, a better insight into its dys-regulation and uncoupling in human disease. Already-approved PDE5 inhibitors and novel, first-in-class molecules, which up-regulate the activity of sGC independently of NO and/or of the enzyme's haem prosthetic group, are undergoing clinical evaluation to treat pulmonary hypertension and myocardial failure. These molecules, as well as combinations or second-generation compounds, are also being assessed in additional experimental disease models and in patients in a wide spectrum of novel indications, such as endotoxic shock, diabetic cardiomyopathy and Becker's muscular dystrophy. There is well-founded optimism that the modulation of the NO-sGC-cGMP pathway will sustain the development of an increasing number of successful clinical candidates for years to come. © 2014 The British Pharmacological Society.",
    title = "Extending the translational potential of targeting NO/cGMP-regulated pathways in the CVS",
    doi = "10.1111/BPH.12980"
}