ArticleJournal of medicinal chemistry2015
Structure-Activity Relationship Studies of Substituted 2-(Isoxazol-3-yl)-2-oxo-N'-phenyl-acetohydrazonoyl Cyanide Analogues: Identification of Potent Exchange Proteins Directly Activated by cAMP (EPAC) Antagonists.
Article in Journal of medicinal chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 39 citations in OpenAlex.
- Role of exchange proteins directly activated by cAMP signaling in vascular remodeling.Pharmacological reviews · 2025Review
- Intracellular receptor EPAC regulates von Willebrand factor secretion from endothelial cells in a PI3K-/eNOS-dependent manner during inflammation.The Journal of biological chemistry · 2021Article
- Exchange Protein Directly Activated by cAMP 2 Enhances Respiratory Syncytial Virus-Induced Pulmonary Disease in Mice.Frontiers in immunology · 2021Article
- Review
- Targeting the Small GTPase Superfamily through Their Regulatory Proteins.Angewandte Chemie (International ed. in English) · 2020Review
- Neuronal Epac1 mediates retinal neurodegeneration in mouse models of ocular hypertension.The Journal of experimental medicine · 2020Article
- Review
- Exchange Protein Directly Activated by cAMP Modulates Ebola Virus Uptake into Vascular Endothelial Cells.Viruses · 2018Article
- Intracellular cAMP Sensor EPAC: Physiology, Pathophysiology, and Therapeutics Development.Physiological reviews · 2018Review
- EPAC1 regulates endothelial annexin A2 cell surface translocation and plasminogen activation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Effects of rigidity on the selectivity of protein kinase inhibitors.European journal of medicinal chemistry · 2018Article
- The synthetic and therapeutic expedition of isoxazole and its analogs.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2018Review
- The Potential of a Novel Class of EPAC-Selective Agonists to Combat Cardiovascular Inflammation.Journal of cardiovascular development and disease · 2017Review
- Structure-activity relationships of 2-substituted phenyl-N-phenyl-2-oxoacetohydrazonoyl cyanides as novel antagonists of exchange proteins directly activated by cAMP (EPACs).Bioorganic & medicinal chemistry letters · 2017Article
- A cell-based, quantitative and isoform-specific assay for exchange proteins directly activated by cAMP.Scientific reports · 2017Article
- Identification of novel 2-(benzo[d]isoxazol-3-yl)-2-oxo-N-phenylacetohydrazonoyl cyanide analoguesas potent EPAC antagonists.European journal of medicinal chemistry · 2017Article
- Exchange proteins directly activated by cAMP (EPACs): Emerging therapeutic targets.Bioorganic & medicinal chemistry letters · 2017Review
- Therapeutic Potential of Spirooxindoles as Antiviral Agents.ACS infectious diseases · 2016Review
- Functionalized N,N-Diphenylamines as Potent and Selective EPAC2 Inhibitors.ACS medicinal chemistry letters · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Exchange proteins directly activated by cAMP (EPAC) as guanine nucleotide exchange factors mediate the effects of the pivotal second messenger cAMP, thereby regulating a wide variety of intracellular physiological and pathophysiological processes. A series of novel 2-(isoxazol-3-yl)-2-oxo-N'-phenyl-acetohydrazonoyl cyanide EPAC antagonists was synthesized and evaluated in an effort to optimize properties of the previously identified high-throughput (HTS) hit 1 (ESI-09). Structure-activity relationship (SAR) analysis led to the discovery of several more active EPAC antagonists (e.g., 22 (HJC0726), 35 (NY0123), and 47 (NY0173)) with low micromolar inhibitory activity. These inhibitors may serve as valuable pharmacological probes to facilitate our efforts in elucidating the biological functions of EPAC and developing potential novel therapeutics against human diseases. Our SAR results have also revealed that further modification at the 3-, 4-, and 5-positions of the phenyl ring as well as the 5-position of the isoxazole moiety may allow for the development of more potent EPAC antagonists.
Indexed as
Identifiers
What OpenQuestion holds
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.