Adenylate cyclase (or adenylyl cyclase; EC 4.6.1.1), an enzyme with key regulatory roles in essentially all cells, is a member of the family of P-O lyases . At least nine closely related isoforms of adenylate cyclases (ACs), the enzymes responsible for the synthesis of cyclic AMP (cAMP) from ATP, have been cloned and characterized in mammals. In addition to their ability to respond to Gαs and to FSK, the different isoforms can receive signals from a variety of sources, including other G proteins, e.g. Gαi and Gβγ, protein kinases (PKA, PKC, and calmodulin (CaM) kinase), phosphatases (calcineurin), calcium, and Ca2+/CaM, and these isoforms are able to support and integrate differential regulatory pathways through cross-talk with other signal transduction systems. All isoforms are expressed in brain cells, although the expression of any individual isoform is restricted to discrete structures of the central nervous system. In the peripheral tissues, the pattern of AC expression is more specific[1]. Although many drugs inhibit or stimulate AC activity through the respective upstream G-protein coupled 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[2]. Besides the nine transmembrane enzymes, one soluble AC (sAC) exists. Mammalian sAC has been implicated in processes such as sperm activation, glucosemetabolism, and prostate and skin cancer, making it a potential therapeutic target[3].