cGMP-dependent protein kinases in drug discovery

Drug Discov Today. 2005 May 1;10(9):627-34. doi: 10.1016/S1359-6446(05)03406-9.


Cyclic guanosine-3', 5'-monophosphate (cGMP)-dependent protein kinases (cGKs) are key enzymes of nitric oxide-cGMP and natriuretic peptide signalling cascades. These kinases mediate most of the effects of cGMP-elevating drugs, such as nitrates and phosphodiesterase inhibitors. cGKs modulate smooth muscle relaxation (e.g. the vasculature, gastrointestinal tract, bladder and penile), platelet aggregation, renin release, intestinal secretion, learning and memory. Furthermore, several cGK substrates have been identified. Isozyme-specific inhibitors and activators of cGK and its downstream substrates might act more specifically than upstream signalling activators, such as organic nitrates and phosphodiesterase inhibitors.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Blood Platelets / enzymology
  • Chemistry, Pharmaceutical
  • Cyclic GMP-Dependent Protein Kinases* / antagonists & inhibitors
  • Cyclic GMP-Dependent Protein Kinases* / metabolism
  • Drug Delivery Systems*
  • Drug Design*
  • Humans
  • Muscle, Smooth / enzymology
  • Nervous System / enzymology
  • Signal Transduction


  • Cyclic GMP-Dependent Protein Kinases