ArticlePloS one2017
Small molecule inhibitors of mesotrypsin from a structure-based docking screen.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 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.
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
10 citing papers in PubMed, 21 citations in OpenAlex.
- Discovery of an autoinhibited conformation in mesotrypsin reveals a strategy for selective serine protease inhibition.Science advances · 2025Article
- Serine protease inhibitors decrease metastasis in prostate, breast, and ovarian cancers.Molecular oncology · 2023Article
- Shear Stress Drives the Cleavage Activation of Protease-Activated Receptor 2 by PRSS3/Mesotrypsin to Promote Invasion and Metastasis of Circulating Lung Cancer Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- COVID-19 and Diarylamidines: The Parasitic Connection.International journal of molecular sciences · 2023Review
- Target identification for repurposed drugs active against SARS-CoV-2 via high-throughput inverse docking.Journal of computer-aided molecular design · 2022Article
- Serine Protease 3 Promotes Progression of Diffuse Large B-Cell Lymphoma and Serves as a Novel Prognostic Predictor.Disease markers · 2022Article
- Potent Inhibitor of Human Trypsins from the Aeruginosin Family of Natural Products.ACS chemical biology · 2021Article
- A Virtual Screening Platform Identifies Chloroethylagelastatin A as a Potential Ribosomal Inhibitor.Biomolecules · 2020Article
- PRSS3/Mesotrypsin and kallikrein-related peptidase 5 are associated with poor prognosis and contribute to tumor cell invasion and growth in lung adenocarcinoma.Scientific reports · 2019Article
- Proteases: Pivot Points in Functional Proteomics.Methods in molecular biology (Clifton, N.J.) · 2019Review
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
PRSS3/mesotrypsin is an atypical isoform of trypsin, the upregulation of which has been implicated in promoting tumor progression. To date there are no mesotrypsin-selective pharmacological inhibitors which could serve as tools for deciphering the pathological role of this enzyme, and could potentially form the basis for novel therapeutic strategies targeting mesotrypsin. A virtual screen of the Natural Product Database (NPD) and Food and Drug Administration (FDA) approved Drug Database was conducted by high-throughput molecular docking utilizing crystal structures of mesotrypsin. Twelve high-scoring compounds were selected for testing based on lowest free energy docking scores, interaction with key mesotrypsin active site residues, and commercial availability. Diminazene (CID22956468), along with two similar compounds presenting the bis-benzamidine substructure, was validated as a competitive inhibitor of mesotrypsin and other human trypsin isoforms. Diminazene is the most potent small molecule inhibitor of mesotrypsin reported to date with an inhibitory constant (Ki) of 3.6±0.3 μM. Diminazene was subsequently co-crystalized with mesotrypsin and the crystal structure was solved and refined to 1.25 Å resolution. This high resolution crystal structure can now offer a foundation for structure-guided efforts to develop novel and potentially more selective mesotrypsin inhibitors based on similar molecular substructures.
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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.