ArticleJournal of the American Chemical Society2014
Identification of biologically active, HIV TAR RNA-binding small molecules using small molecule microarrays.
Article in Journal of the American Chemical Society, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.
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
86 citing papers in PubMed, 1 synthesis or guideline pooled it, 141 citations in OpenAlex.
- RNA Drugs and RNA Targets for Small Molecules: Principles, Progress, and Challenges.Pharmacological reviews · 2020Pooled it
- Regulatable in vivo gene expression via adaptamers.Molecular cell · 2026Article
- Linker Optimization of cMYC RIBOTAC for Efficient cMYC Modulation.ChemMedChem · 2026Article
- Decoding the Structural Complexity of Viral RNAs with SHAPE to Guide Antiviral Therapeutics.Viruses · 2026Review
- An orthogonal RNA aptamer for targeted RNA regulation in phase-separated subcellular compartments.Nature communications · 2026Article
- Decoding RNA Structural Ensembles: Energy Landscape Exploration of the TAR Stemloop.Journal of chemical theory and computation · 2026Article
- RNP interfaces as regulatory "active sites": a repurposing strategy for small molecules targeting viral 5'-untranslated regions.Frontiers in molecular biosciences · 2026Article
- Integrative In Silico and In Vitro Screening of Low Molecular Weight Compounds Targeting SARS-CoV-2 RNA Elements.Chembiochem : a European journal of chemical biology · 2025Article
- Mechanistic studies of small molecule ligands selective to RNA single G bulges.Nucleic acids research · 2025Article
- Article
- ShiftScan: A tool for rapid analysis of high-throughput differential scanning fluorimetry data and compound prioritization.Protein science : a publication of the Protein Society · 2025Article
- Novel Quinazoline Derivatives Inhibit Splicing of Fungal Group II Introns.ACS chemical biology · 2025Article
- Use of a small molecule microarray screen to identify inhibitors of the catalytic RNA subunit of Methanobrevibacter smithii RNase P.Nucleic acids research · 2025Article
- HIV-Tat and vascular endothelium: implications in the HIV associated brain, heart, and lung complications.Frontiers in immunology · 2025Review
- Technologies for Targeted RNA Degradation and Induced RNA Decay.Chemical reviews · 2024Review
- Harnessing Computational Approaches for RNA-Targeted Drug Discovery.RNA nanomed · 2024Article
- Targeting RNA with small molecules, from RNA structures to precision medicines: IUPHAR review: 40.British journal of pharmacology · 2024Review
- A specific domain within the 3' untranslated region of Usutu virus confers resistance to the exonuclease ISG20.Nature communications · 2024Article
- Targeting MicroRNAs with Small Molecules.Non-coding RNA · 2024Review
- Small Molecules Targeting Viral RNA.International journal of molecular sciences · 2023Review
26 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Identifying small molecules that selectively bind to structured RNA motifs remains an important challenge in developing potent and specific therapeutics. Most strategies to find RNA-binding molecules have identified highly charged compounds or aminoglycosides that commonly have modest selectivity. Here we demonstrate a strategy to screen a large unbiased library of druglike small molecules in a microarray format against an RNA target. This approach has enabled the identification of a novel chemotype that selectively targets the HIV transactivation response (TAR) RNA hairpin in a manner not dependent on cationic charge. Thienopyridine 4 binds to and stabilizes the TAR hairpin with a Kd of 2.4 μM. Structure-activity relationships demonstrate that this compound achieves activity through hydrophobic and aromatic substituents on a heterocyclic core, rather than cationic groups typically required. Selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) analysis was performed on a 365-nucleotide sequence derived from the 5' untranslated region (UTR) of the HIV-1 genome to determine global structural changes in the presence of the molecule. Importantly, the interaction of compound 4 can be mapped to the TAR hairpin without broadly disrupting any other structured elements of the 5' UTR. Cell-based anti-HIV assays indicated that 4 inhibits HIV-induced cytopathicity in T lymphocytes with an EC50 of 28 μM, while cytotoxicity was not observed at concentrations approaching 1 mM.
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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.