ArticleJournal of medicinal chemistry2009
A basis for reduced chemical library inhibition of firefly luciferase obtained from directed evolution.
Article in Journal of medicinal chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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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
31 citing papers in PubMed, 82 citations in OpenAlex.
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- Development of compounds for targeted degradation of mammalian cryptochrome proteins.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2025Article
- Degradation of neurodegenerative disease-associated TDP-43 aggregates and oligomers via a proteolysis-targeting chimera.Journal of biomedical science · 2023Article
- Utility of Bioluminescent Homogeneous Nucleotide Detection Assays in Measuring Activities of Nucleotide-Sugar Dependent Glycosyltransferases and Studying Their Inhibitors.Molecules (Basel, Switzerland) · 2021Article
- A novel thermostable beetle luciferase based cytotoxicity assay.Scientific reports · 2021Article
- Decreasing HepG2 Cytotoxicity by Lowering the Lipophilicity of Benzo[d]oxazolephosphinate Ester Utrophin Modulators.ACS medicinal chemistry letters · 2020Article
- Challenges and Opportunities in Preclinical Research of Synthetic Cannabinoids for Pain Therapy.Medicina (Kaunas, Lithuania) · 2020Review
- 5,5-Dialkylluciferins are thermal stable substrates for bioluminescence-based detection systems.PloS one · 2020Article
- Integrating Machine Learning-Based Virtual Screening With Multiple Protein Structures and Bio-Assay Evaluation for Discovery of Novel GSK3β Inhibitors.Frontiers in pharmacology · 2020Article
- Quantitative High-Throughput Screening Using a Coincidence Reporter Biocircuit.Current protocols in neuroscience · 2017Article
- Real-time monitoring of cisplatin cytotoxicity on three-dimensional spheroid tumor cells.Drug design, development and therapy · 2016Article
- Bioluminescence Methods for Assaying Kinases in Quantitative High-Throughput Screening (qHTS) Format Applied to Yes1 Tyrosine Kinase, Glucokinase, and PI5P4Kα Lipid Kinase.Methods in molecular biology (Clifton, N.J.) · 2016Article
- Design, Synthesis and Inhibitory Activity of Photoswitchable RET Kinase Inhibitors.Scientific reports · 2015Article
- Total Synthesis and Biological Studies of TMC-205 and Analogues as Anticancer Agents and Activators of SV40 Promoter.ACS medicinal chemistry letters · 2014Article
- A homogeneous, high-throughput assay for phosphatidylinositol 5-phosphate 4-kinase with a novel, rapid substrate preparation.PloS one · 2013Article
- The nuclear factor κB inhibitor (E)-2-fluoro-4'-methoxystilbene inhibits firefly luciferase.Bioscience reports · 2012Article
- Engineered luciferase reporter from a deep sea shrimp utilizing a novel imidazopyrazinone substrate.ACS chemical biology · 2012Article
- Firefly luciferase in chemical biology: a compendium of inhibitors, mechanistic evaluation of chemotypes, and suggested use as a reporter.Chemistry & biology · 2012Article
- Titration-based screening for evaluation of natural product extracts: identification of an aspulvinone family of luciferase inhibitors.Chemistry & biology · 2011Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
We measured the "druggability" of the ATP-dependent luciferase derived from the firefly Photuris pennsylvanica that was optimized using directed evolution (Ultra-Glo, Promega). Quantitative high-throughput screening (qHTS) was used to determine IC(50)s of 198899 samples against a formulation of Ultra-Glo luciferase (Kinase-Glo). We found that only 0.1% of the Kinase-Glo inhibitors showed an IC(50) < 10 microM compared to 0.9% found from a previous qHTS against the firefly luciferase from Photinus pyralis (lucPpy). Further, the maximum affinity identified in the lucPpy qHTS was 50 nM, while for Kinase-Glo this value increased to 600 nM. Compounds with interactions stretching outside the luciferin binding pocket were largely lost with Ultra-Glo luciferase. Therefore, Ultra-Glo luciferase will show less compound interference when used as an ATP sensor compared to lucPpy. This study demonstrates the power of large-scale quantitative analysis of structure-activity relationships (>100K compounds) in addressing important questions such as a target's druggability.
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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.