Inhibitors of membranous adenylyl cyclases.

ABSTRACT: Membranous adenylyl cyclases (mACs) constitute a family of nine isoforms with different expression patterns. Studies with mAC gene knockout mice provide evidence for the notion that AC isoforms play distinct (patho)physiological roles. Consequently, there is substantial interest in the development of isoform-selective mAC inhibitors. Here, we review the current literature on mAC inhibitors. Structurally diverse inhibitors targeting the catalytic site and allosteric sites (e.g. the diterpene site) have been identified. The catalytic site of mACs accommodates both purine and pyrimidine nucleotides, with a hydrophobic pocket constituting a major affinity-conferring domain for substituents at the 2'- and 3'-O-ribosyl position of nucleotides. BODIPY-forskolin stimulates ACs 1 and 5 but inhibits

SUBMITTER: Seifert R 

PROVIDER: S-EPMC3273670 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature