ArticleMethods in enzymology2016
High-Throughput Screening for Drugs that Modulate Intermediate Filament Proteins.
Article in Methods in enzymology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 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
11 citing papers in PubMed, 17 citations in OpenAlex.
- Intermediate filaments and their associated molecules.Journal of biomedical research · 2025Article
- Deacetylation via SIRT2 prevents keratin-mutation-associated injury and keratin aggregation.JCI insight · 2023Article
- A cell-based drug discovery assay identifies inhibition of cell stress responses as a new approach to treatment of epidermolysis bullosa simplex.Journal of cell science · 2021Article
- Recent insight into intermediate filament structure.Current opinion in cell biology · 2021Review
- Molecular Modeling of Pathogenic Mutations in the Keratin 1B Domain.International journal of molecular sciences · 2020Article
- Targeting and extending the eukaryotic druggable genome with natural products: cytoskeletal targets of natural products.Natural product reports · 2020Review
- Crystal Structure of Keratin 1/10(C401A) 2B Heterodimer Demonstrates a Proclivity for the C-Terminus of Helix 2B to Form Higher Order Molecular Contacts.The Yale journal of biology and medicine · 2020Article
- Intermediate filaments and IF-associated proteins: from cell architecture to cell proliferation.Proceedings of the Japan Academy. Series B, Physical and biological sciences · 2019Review
- Nuclear lamina genetic variants, including a truncated LAP2, in twins and siblings with nonalcoholic fatty liver disease.Hepatology (Baltimore, Md.) · 2018Article
- Intermediate filament proteins of digestive organs: physiology and pathophysiology.American journal of physiology. Gastrointestinal and liver physiology · 2017Review
- Multiple roles for keratin intermediate filaments in the regulation of epithelial barrier function and apico-basal polarity.Tissue barriersReview
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Intermediate filament (IF) proteins have unique and complex cell and tissue distribution. Importantly, IF gene mutations cause or predispose to more than 80 human tissue-specific diseases (IF-pathies), with the most severe disease phenotypes being due to mutations at conserved residues that result in a disrupted IF network. A critical need for the entire IF-pathy field is the identification of drugs that can ameliorate or cure these diseases, particularly since all current therapies target the IF-pathy complication, such as diabetes or cardiovascular disease, rather than the mutant IF protein or gene. We describe a high-throughput approach to identify drugs that can normalize disrupted IF proteins. This approach utilizes transduction of lentivirus that expresses green fluorescent protein-tagged keratin 18 (K18) R90C in A549 cells. The readout is drug "hits" that convert the dot-like keratin filament distribution, due to the R90C mutation, to a wild-type-like filamentous array. A similar strategy can be used to screen thousands of compounds and can be utilized for practically any IF protein with a filament-disrupting mutation, and could therefore potentially target many IF-pathies. "Hits" of interest require validation in cell culture then using in vivo experimental models. Approaches to study the mechanism of mutant IF normalization by potential drugs of interest are also described. The ultimate goal of this drug screening approach is to identify effective and safe compounds that can potentially be tested for clinical efficacy in patients.
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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.