ArticleJournal of medicinal chemistry2015
Virtual High-Throughput Screening To Identify Novel Activin 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 12 papers.
What it found
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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.
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.
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Who cites it
12 citing papers in PubMed, 20 citations in OpenAlex.
- Development of a SIN1 Targeting Inhibitor as a Novel Therapeutic Approach for the Treatment of Malignancies.Molecular cancer therapeutics · 2026Article
- Research progress and challenges of molecular recognition techniques in the screening of active ingredients in Traditional Chinese medicine.Journal of pharmaceutical analysis · 2025Review
- Antagonizing Activin A/p15Cells · 2024Article
- A Comprehensive Survey of Prospective Structure-Based Virtual Screening for Early Drug Discovery in the Past Fifteen Years.International journal of molecular sciences · 2022Review
- Development of ovarian tumour causes significant loss of muscle and adipose tissue: a novel mouse model for cancer cachexia study.Journal of cachexia, sarcopenia and muscle · 2022Article
- Dual Roles of the Activin Signaling Pathway in Pancreatic Cancer.Biomedicines · 2021Review
- Discovery of novel Mnk inhibitors using mutation-based induced-fit virtual high-throughput screening.Chemical biology & drug design · 2019Article
- Activin A stimulates migration of the fallopian tube epithelium, an origin of high-grade serous ovarian cancer, through non-canonical signaling.Cancer letters · 2017Article
- Exploring the Molecular Basis for Binding of Inhibitors by Threonyl-tRNA Synthetase from Brucella abortus: A Virtual Screening Study.International journal of molecular sciences · 2016Article
- Inhibitors of pendrin anion exchange identified in a small molecule screen increase airway surface liquid volume in cystic fibrosis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2016Article
- Docking Screens for Novel Ligands Conferring New Biology.Journal of medicinal chemistry · 2016Review
- Computational methods in drug discovery.Beilstein journal of organic chemistry · 2016Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 1 institution in 2 countries.
Funding
Abstract
Activin belongs to the TGFβ superfamily, which is associated with several disease conditions, including cancer-related cachexia, preterm labor with delivery, and osteoporosis. Targeting activin and its related signaling pathways holds promise as a therapeutic approach to these diseases. A small-molecule ligand-binding groove was identified in the interface between the two activin βA subunits and was used for a virtual high-throughput in silico screening of the ZINC database to identify hits. Thirty-nine compounds without significant toxicity were tested in two well-established activin assays: FSHβ transcription and HepG2 cell apoptosis. This screening workflow resulted in two lead compounds: NUCC-474 and NUCC-555. These potential activin antagonists were then shown to inhibit activin A-mediated cell proliferation in ex vivo ovary cultures. In vivo testing showed that our most potent compound (NUCC-555) caused a dose-dependent decrease in FSH levels in ovariectomized mice. The Blitz competition binding assay confirmed target binding of NUCC-555 to the activin A:ActRII that disrupts the activin A:ActRII complex's binding with ALK4-ECD-Fc in a dose-dependent manner. The NUCC-555 also specifically binds to activin A compared with other TGFβ superfamily member myostatin (GDF8). These data demonstrate a new in silico-based strategy for identifying small-molecule activin antagonists. Our approach is the first to identify a first-in-class small-molecule antagonist of activin binding to ALK4, which opens a completely new approach to inhibiting the activity of TGFβ receptor superfamily members. in addition, the lead compound can serve as a starting point for lead optimization toward the goal of a compound that may be effective in activin-mediated diseases.
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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.