ArticleCombinatorial chemistry & high throughput screening2014
A 1536-well fluorescence polarization assay to screen for modulators of the MUSASHI family of RNA-binding proteins.
Article in Combinatorial chemistry & high throughput screening, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 37 citations in OpenAlex.
- The cellular landscape of druggable RNA-binding proteins.Nature reviews. Drug discovery · 2026Review
- Ro 08-2750 increases radiation-induced cytotoxicity in DLBCL by dysregulating the DNA damage response.Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al] · 2026Article
- Targeting RNA binding proteins with small-molecule inhibitors: Advances, challenges, and therapeutic opportunities.Acta pharmaceutica Sinica. B · 2026Review
- Review
- Small-molecule Ro-08-2750 interacts with many RNA-binding proteins and elicits MUSASHI2-independent phenotypes.RNA (New York, N.Y.) · 2023Article
- The Musashi RNA-binding proteins in female cancers: insights on molecular mechanisms and therapeutic relevance.Biomarker research · 2023Review
- Development and clinical advancement of small molecules forActa pharmaceutica Sinica. B · 2022Review
- New approaches to target RNA binding proteins.Current opinion in chemical biology · 2021Review
- Musashi 2 influences chronic lymphocytic leukemia cell survival and growth making it a potential therapeutic target.Leukemia · 2021Article
- Article
- Potential Role of Musashi-2 RNA-Binding Protein in Cancer EMT.OncoTargets and therapy · 2021Review
- RNA-Binding Proteins as Regulators of Migration, Invasion and Metastasis in Oral Squamous Cell Carcinoma.International journal of molecular sciences · 2020Review
- Identification and Validation of anCancers · 2020Article
- RNA Regulators in Leukemia and Lymphoma.Cold Spring Harbor perspectives in medicine · 2020Review
- RNA-Targeted Therapies and High-Throughput Screening Methods.International journal of molecular sciences · 2020Review
- Cancer the'RBP'eutics-RNA-binding proteins as therapeutic targets for cancer.Pharmacology & therapeutics · 2019Review
- Fluorescence-based investigations of RNA-small molecule interactions.Methods (San Diego, Calif.) · 2019Article
- Small-molecule targeting of MUSASHI RNA-binding activity in acute myeloid leukemia.Nature communications · 2019Article
- MSI2 knockdown represses extrahepatic cholangiocarcinoma growth and invasion by inhibiting epithelial-mesenchymal transition.OncoTargets and therapy · 2018Article
- Human oncoprotein Musashi-2 N-terminal RNA recognition motif backbone assignment and identification of RNA-binding pocket.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
RNA-binding proteins (RBPs) can act as stem cell modulators and oncogenic drivers, but have been largely ignored by the pharmaceutical industry as potential therapeutic targets for cancer. The MUSASHI (MSI) family has recently been demonstrated to be an attractive clinical target in the most aggressive cancers. Therefore, the discovery and development of small molecule inhibitors could provide a novel therapeutic strategy. In order to find novel compounds with MSI RNA binding inhibitory activity, we have developed a fluorescence polarization (FP) assay and optimized it for high throughput screening (HTS) in a 1536-well microtiter plate format. Using a chemical library of 6,208 compounds, we performed pilot screens, against both MSI1 and MSI2, leading to the identification of 7 molecules for MSI1, 15 for MSI2 and 5 that inhibited both. A secondary FP dose-response screen validated 3 MSI inhibitors with IC50 below 10 μM. Out of the 25 compounds retested in the secondary screen only 8 demonstrated optical interference due to high fluorescence. Utilizing a SYBR-based RNA electrophoresis mobility shift assay (EMSA), we further verified MSI inhibition of the top 3 compounds. Surprisingly, even though several aminoglycosides were present in the library, they failed to demonstrate MSI inhibitor activity challenging the concept that these compounds are pan-active against RBPs. In summary, we have developed an in vitro strategy to identify MSI specific inhibitors using an FP HTS platform, which will facilitate novel drug discovery for this class of RBPs.
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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 Socratic graph.