Adenylyl cyclase, E.C. 4.6.1.1, converts ATP to cyclic AMP and pyrophosphate. Mammalian membrane-delimited adenylyl cyclases (nomenclature as approved by the NC-IUPHAR Subcommittee on Adenylyl cyclases [10]) are typically made up of two clusters of six TM domains separating two intracellular, overlapping catalytic domains that are the target for the nonselective activators Gα_s (the stimulatory G protein α subunit) and forskolin (except AC9, [27]). Adenosine and its derivatives (e.g. 2',5'-dideoxyadenosine), acting through the P-site,are inhibitors of adenylyl cyclase activity [34]. Four families of membranous adenylyl cyclase are distinguishable: calmodulin (CALM2, CALM3, CALM1, P62158)-stimulated (AC1, AC3 and AC8), Ca²⁺- and Gβγ-inhibitable (AC5, AC6 and AC9), Gβγ-stimulated and Ca²⁺-insensitive (AC2, AC4 and AC7), and forskolin-insensitive (AC9) forms. A soluble adenylyl cyclase (AC10) lacks membrane spanning regions and is insensitive to G proteins.It functions as a cytoplasmic bicarbonate (pH-insensitive) sensor [6].

Many of the activators and inhibitors listed are only somewhat selective or have not been tested against all AC isoforms [2,9]. AC3 shows only modest in vitro activation by Ca²⁺/CaM.

* Key recommended reading is highlighted with an asterisk

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* Halls ML, Cooper DM. (2017) Adenylyl cyclase signalling complexes - Pharmacological challenges and opportunities. Pharmacol Ther, 172: 171-180. [PMID:28132906]

Johnstone TB, Agarwal SR, Harvey RD, Ostrom RS. (2018) cAMP Signaling Compartmentation: Adenylyl Cyclases as Anchors of Dynamic Signaling Complexes. Mol Pharmacol, 93 (4): 270-276. [PMID:29217670]

* Wiggins SV, Steegborn C, Levin LR, Buck J. (2018) Pharmacological modulation of the CO₂/HCO₃^-/pH-, calcium-, and ATP-sensing soluble adenylyl cyclase. Pharmacol Ther, 190: 173-186. [PMID:29807057]

Wu L, Shen C, Seed Ahmed M, Östenson CG, Gu HF. (2016) Adenylate cyclase 3: a new target for anti-obesity drug development. Obes Rev, 17 (9): 907-14. [PMID:27256589]

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Subcommittee members: Carmen W. Dessauer (Chairperson) Department of Integrative Biology and Pharmacology McGovern Medical School University of Texas Health Science Center Houston, TX 77030, USA. Rennolds Ostrom Department of Pharmacology Department of Biomedical and Pharmaceutical Sciences School of Pharmacy Chapman University Irvine, California Roland Seifert Institute of Pharmacology Medical School of Hannover Carl-Neuberg-Str. 1 D-30625 Hannover Germany Val J. Watts Purdue University Medicinal Chemistry and Molecular Pharmacology, West Lafayette, USA