ArticleJournal of medicinal chemistry2009
Discovery of geranylgeranyltransferase-I inhibitors with novel scaffolds by the means of quantitative structure-activity relationship modeling, virtual screening, and experimental validation.
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 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, 41 citations in OpenAlex.
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- Past and Future Strategies to Inhibit Membrane Localization of the KRAS Oncogene.International journal of molecular sciences · 2021Review
- Molecular and Pharmacological Characterization of the Interaction between Human Geranylgeranyltransferase Type I and Ras-Related Protein Rap1B.International journal of molecular sciences · 2021Article
- Structure-Based Virtual Screening: From Classical to Artificial Intelligence.Frontiers in chemistry · 2020Review
- Cheminfomatic-based Drug Discovery of Human Tyrosine Kinase Inhibitors.Current topics in medicinal chemistry · 2016Review
- Combined rational design and a high throughput screening platform for identifying chemical inhibitors of a Ras-activating enzyme.The Journal of biological chemistry · 2015Article
- Discovery of Natural Product-Derived 5-HT1A Receptor Binders by Cheminfomatics Modeling of Known Binders, High Throughput Screening and Experimental Validation.Combinatorial chemistry & high throughput screening · 2015Article
- Statistical analysis, optimization, and prioritization of virtual screening parameters for zinc enzymes including the anthrax toxin lethal factor.Current topics in medicinal chemistry · 2014Review
- Targeting protein prenylation for cancer therapy.Nature reviews. Cancer · 2011Article
- Software and resources for computational medicinal chemistry.Future medicinal chemistry · 2011Review
- Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Geranylgeranylation is critical to the function of several proteins including Rho, Rap1, Rac, Cdc42, and G-protein gamma subunits. Geranylgeranyltransferase type I (GGTase-I) inhibitors (GGTIs) have therapeutic potential to treat inflammation, multiple sclerosis, atherosclerosis, and many other diseases. Following our standard workflow, we have developed and rigorously validated quantitative structure-activity relationship (QSAR) models for 48 GGTIs using variable selection k nearest neighbor (kNN), automated lazy learning (ALL), and partial least squares (PLS) methods. The QSAR models were employed for virtual screening of 9.5 million commercially available chemicals, yielding 47 diverse computational hits. Seven of these compounds with novel scaffolds and high predicted GGTase-I inhibitory activities were tested in vitro, and all were found to be bona fide and selective micromolar inhibitors. Notably, these novel hits could not be identified using traditional similarity search. These data demonstrate that rigorously developed QSAR models can serve as reliable virtual screening tools, leading to the discovery of structurally novel bioactive compounds.
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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.