ArticleJournal of biomolecular screening2012
High-throughput screening identifies a bisphenol inhibitor of SV40 large T antigen ATPase activity.
Article in Journal of biomolecular screening, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 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
10 citing papers in PubMed.
- The conserved core enzymatic activities and the distinct dynamics of polyomavirus large T antigens.Archives of biochemistry and biophysics · 2015Article
- Benzothiazole and Pyrrolone Flavivirus Inhibitors Targeting the Viral Helicase.ACS infectious diseases · 2015Article
- Inhibition of large T antigen ATPase activity as a potential strategy to develop anti-polyomavirus JC drugs.Antiviral research · 2014Article
- Synthesis and structure–activity relationships of small molecule inhibitors of the simian virus 40 T antigen oncoprotein, an anti-polyomaviral target.Bioorganic & medicinal chemistry · 2014Article
- A BSL-4 high-throughput screen identifies sulfonamide inhibitors of Nipah virus.Assay and drug development technologies · 2014Article
- The Mcm2-7 replicative helicase: a promising chemotherapeutic target.BioMed research international · 2014Review
- Discovering new medicines targeting helicases: challenges and recent progress.Journal of biomolecular screening · 2013Review
- Hsp70 protein complexes as drug targets.Current pharmaceutical design · 2013Review
- A screen for modulators of large T antigen's ATPase activity uncovers novel inhibitors of Simian Virus 40 and BK virus replication.Antiviral research · 2012Article
- Survivin is a therapeutic target in Merkel cell carcinoma.Science translational medicine · 2012Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors.
Funding
Abstract
The authors conducted a high-throughput screening campaign for inhibitors of SV40 large T antigen ATPase activity to identify candidate antivirals that target the replication of polyomaviruses. The primary assay was adapted to 1536-well microplates and used to screen the National Institutes of Health Molecular Libraries Probe Centers Network library of 306 015 compounds. The primary screen had an Z value of ~0.68, signal/background = 3, and a high (5%) DMSO tolerance. Two counterscreens and two secondary assays were used to prioritize hits by EC(50), cytotoxicity, target specificity, and off-target effects. Hits that inhibited ATPase activity by >44% in the primary screen were tested in dose-response efficacy and eukaryotic cytotoxicity assays. After evaluation of hit cytotoxicity, drug likeness, promiscuity, and target specificity, three compounds were chosen for chemical optimization. Chemical optimization identified a class of bisphenols as the most effective biochemical inhibitors. Bisphenol A inhibited SV40 large T antigen ATPase activity with an IC(50) of 41 µM in the primary assay and 6.2 µM in a cytoprotection assay. This compound class is suitable as probes for biochemical investigation of large T antigen ATPase activity, but because of their cytotoxicity, further optimization is necessary for their use in studying polyomavirus replication in vivo.
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.