Capturing adenylyl cyclases as potential drug targets

Nat Rev Drug Discov. 2009 Apr;8(4):321-35. doi: 10.1038/nrd2827.


Cyclic AMP (cAMP) is an important intracellular signalling mediator. It is generated in mammals by nine membrane-bound and one soluble adenylyl cyclases (ACs), each with distinct regulation and expression patterns. Although many drugs inhibit or stimulate AC activity through the respective upstream G-protein coupled receptors (for example, opioid or beta-adrenergic receptors), ACs themselves have not been major drug targets. Over the past decade studies on the physiological functions of the different mammalian AC isoforms as well as advances in the development of isoform-selective AC inhibitors and activators suggest that ACs could be useful drug targets. Here we discuss the therapeutic potential of isoform-selective compounds in various clinical settings, including neuropathic pain, neurodegenerative disorders, congestive heart failure, asthma and male contraception.

Publication types

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

MeSH terms

  • Adenylyl Cyclase Inhibitors
  • Adenylyl Cyclases / metabolism*
  • Animals
  • Drug Delivery Systems / methods*
  • Drug Delivery Systems / trends
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / metabolism
  • Humans
  • Neurodegenerative Diseases / drug therapy
  • Neurodegenerative Diseases / enzymology
  • Pain / drug therapy
  • Pain / enzymology
  • Signal Transduction / physiology


  • Adenylyl Cyclase Inhibitors
  • Enzyme Inhibitors
  • Adenylyl Cyclases