ArticleThe Journal of pharmacology and experimental therapeutics2013
Development of a high-throughput screening paradigm for the discovery of small-molecule modulators of adenylyl cyclase: identification of an adenylyl cyclase 2 inhibitor.
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 21 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
21 citing papers in PubMed, 40 citations in OpenAlex.
- A genetic variant of adenylate cyclase 7 associated with ulcerative colitis shows impaired function and G-protein-coupled receptor signaling.Human genetics · 2026Article
- A signal transduction blind spot: the function of adenylyl cyclase transmembrane domains.The FEBS journal · 2025Review
- Biochemical pharmacology of adenylyl cyclases in cancer.Biochemical pharmacology · 2024Review
- Discovery of a potent and selective human AC2 inhibitor based on 7-deazapurine analogues of adefovir.Bioorganic & medicinal chemistry · 2023Article
- Unusual phototransduction via cross-motif signaling from GProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Physiological roles of mammalian transmembrane adenylyl cyclase isoforms.Physiological reviews · 2022Review
- Halogen-Dance-Based Synthesis of Phosphonomethoxyethyl (PME) Substituted 2-Aminothiazoles as Potent Inhibitors of Bacterial Adenylate Cyclases.ChemMedChem · 2022Article
- Acyclic nucleoside phosphonates with 2-aminothiazole base as inhibitors of bacterial and mammalian adenylate cyclases.European journal of medicinal chemistry · 2021Article
- Pharmacological modulation of the COPharmacology & therapeutics · 2018Review
- Dop1 enhances conspecific olfactory attraction by inhibiting miR-9a maturation in locusts.Nature communications · 2018Article
- International Union of Basic and Clinical Pharmacology. CI. Structures and Small Molecule Modulators of Mammalian Adenylyl Cyclases.Pharmacological reviews · 2017Review
- βNature chemical biology · 2017Article
- Identification of a selective small-molecule inhibitor of type 1 adenylyl cyclase activity with analgesic properties.Science signaling · 2017Article
- Complementary Approaches to Existing Target Based Drug Discovery for Identifying Novel Drug Targets.Biomedicines · 2016Review
- Design and Synthesis of Fluorescent Acyclic Nucleoside Phosphonates as Potent Inhibitors of Bacterial Adenylate Cyclases.ChemMedChem · 2016Article
- Discovery of LRE1 as a specific and allosteric inhibitor of soluble adenylyl cyclase.Nature chemical biology · 2016Article
- Article
- Systems Biomedicine of Rabies Delineates the Affected Signaling Pathways.Frontiers in microbiology · 2016Article
- Cyclic Adenosine 3',5'-Monophosphate Elevation and Biological Signaling through a Secretin Family Gs-Coupled G Protein-Coupled Receptor Are Restricted to a Single Adenylate Cyclase Isoform.Molecular pharmacology · 2015Article
- The role of adenylyl cyclase isoform 6 in β-adrenoceptor signalling in murine airways.British journal of pharmacology · 2015Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Adenylyl cyclase (AC) isoforms are implicated in several physiologic processes and disease states, but advancements in the therapeutic targeting of AC isoforms have been limited by the lack of potent and isoform-selective small-molecule modulators. The discovery of AC isoform-selective small molecules is expected to facilitate the validation of AC isoforms as therapeutic targets and augment the study of AC isoform function in vivo. Identification of chemical probes for AC2 is particularly important because there are no published genetic deletion studies and few small-molecule modulators. The present report describes the development and implementation of an intact-cell, small-molecule screening approach and subsequent validation paradigm for the discovery of AC2 inhibitors. The NIH clinical collections I and II were screened for inhibitors of AC2 activity using PMA-stimulated cAMP accumulation as a functional readout. Active compounds were subsequently confirmed and validated as direct AC2 inhibitors using orthogonal and counterscreening assays. The screening effort identified SKF-83566 [8-bromo-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin-7-ol hydrobromide] as a selective AC2 inhibitor with superior pharmacological properties for selective modulation of AC2 compared with currently available AC inhibitors. The utility of SKF-83566 as a small-molecule probe to study the function of endogenous ACs was demonstrated in C2C12 mouse skeletal muscle cells and human bronchial smooth muscle cells.
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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.