ArticleThe Journal of pharmacology and experimental therapeutics2013
Isoform selectivity of adenylyl cyclase inhibitors: characterization of known and novel compounds.
Article in The Journal of pharmacology and experimental therapeutics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 83 citations in OpenAlex.
- Macrophage adenylyl cyclase 7 protects against myocardial ischemia/reperfusion injury in male mice.Nature communications · 2026Article
- Crosstalk of noradrenergic CaCell communication and signaling : CCS · 2026Article
- Beef-Derived Peptides Mediated Desensitization of Bitter Taste Receptor T2R14 Through GPCR Kinase 2.Nutrients · 2026Article
- Metabolic STAMP for deciphering GPCR-regulated insulin secretion by pancreatic β cells.bioRxiv : the preprint server for biology · 2025Article
- Pyrazolo-Pyrimidinones with Improved Solubility and Selective Inhibition of Adenylyl Cyclase Type 1 Activity for Treatment of Inflammatory Pain.Journal of medicinal chemistry · 2024Article
- Biochemical pharmacology of adenylyl cyclases in cancer.Biochemical pharmacology · 2024Review
- Structure of adenylyl cyclase 5 in complex with Gβγ offers insights into ADCY5-related dyskinesia.Nature structural & molecular biology · 2024Article
- GDF15 controls primary cilia morphology and function thereby affecting progenitor proliferation.Life science alliance · 2024Article
- Adenylyl cyclase isoforms 5 and 6 in the cardiovascular system: complex regulation and divergent roles.Frontiers in pharmacology · 2024Review
- A Critical Appraisal of the Most Recent Investigations on Ora-Pro-Nobis (Plants (Basel, Switzerland) · 2023Review
- Role of cAMP in Cardiomyocyte Viability: Beneficial or Detrimental?Circulation research · 2023Article
- Caveolae-associated cAMP/CaJournal of molecular and cellular cardiology · 2023Article
- Preferential Expression of CaBiomolecules · 2022Article
- Physiological roles of mammalian transmembrane adenylyl cyclase isoforms.Physiological reviews · 2022Review
- Optimization of a Pyrimidinone Series for Selective Inhibition of CaJournal of medicinal chemistry · 2022Article
- A Selective Adenylyl Cyclase 1 Inhibitor Relieves Pain Without Causing Tolerance.Frontiers in pharmacology · 2022Article
- The role of the type 7 adenylyl cyclase isoform in alcohol use disorder and depression.Frontiers in pharmacology · 2022Review
- Acyclic nucleoside phosphonates with 2-aminothiazole base as inhibitors of bacterial and mammalian adenylate cyclases.European journal of medicinal chemistry · 2021Article
- Depolarization induces nociceptor sensitization by CaV1.2-mediated PKA-II activation.The Journal of cell biology · 2021Article
- Insights into the Regulatory Properties of Human Adenylyl Cyclase Type 9.Molecular pharmacology · 2019Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
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-arabinofuranoside (Ara-A), described as supposedly AC5-selective, do not discriminate between AC5 and AC6, whereas the putative AC1-selective inhibitor 5-[[2-(6-amino-9H-purin-9-yl)ethyl]amino]-1-pentanol (NB001) does not directly target AC1 to reduce cAMP levels. A structure-based virtual screen targeting the ATP binding site of AC was used to identify novel chemical structures that show some preference for AC1 or AC2. Mutation of the AC2 forskolin binding pocket does not interfere with inhibition by SQ22,536 or the novel AC2 inhibitor, suggesting binding to the catalytic site. Thus, we show that compounds lacking the adenine chemical signature and targeting the ATP binding site can potentially be used to develop AC isoform-specific inhibitors, and discuss the need to reinterpret literature using AC5/6-selective molecules SQ22,536, NKY80, and Ara-A.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.