Isoform selectivity of adenylyl cyclase inhibitors: characterization of known and novel compounds.

ABSTRACT: Nine membrane-bound adenylyl cyclase (AC) isoforms catalyze the production of the second messenger cyclic AMP (cAMP) in response to various stimuli. Reduction of AC activity has well documented benefits, including benefits for heart disease and pain. These roles have inspired development of isoform-selective AC inhibitors, a lack of which currently limits exploration of functions and/or treatment of dysfunctions involving AC/cAMP signaling. However, inhibitors described as AC5- or AC1-selective have not been screened against the full panel of AC isoforms. We have measured pharmacological inhibitor profiles for all transmembrane AC isoforms. We found that 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ22,536), 2-amino-7-(furanyl)-7,8-dihydro-5(6H)-quinazolinone (NKY80), and adenine 9-β-d-arab

SUBMITTER: Brand CS 

PROVIDER: S-EPMC3807061 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature