ArticleACS chemical biology2008
DcpS as a therapeutic target for spinal muscular atrophy.
Article in ACS chemical biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers, 2 of them syntheses that pooled it.
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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
57 citing papers in PubMed, 2 syntheses or guidelines pooled it, 131 citations in OpenAlex.
- Drug treatment for spinal muscular atrophy types II and III.The Cochrane database of systematic reviews · 2020Pooled it
- Drug treatment for spinal muscular atrophy type I.The Cochrane database of systematic reviews · 2019Pooled it
- Article
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- Aptamer-based assay for high-throughput substrate profiling of RNA decapping enzymes.Nucleic acids research · 2024Article
- Nsp14 of SARS-CoV-2 inhibits mRNA processing and nuclear export by targeting the nuclear cap-binding complex.Nucleic acids research · 2023Article
- Synthesis and Evaluation of Diguanosine Cap Analogs Modified at the C8-Position by Suzuki-Miyaura Cross-Coupling: Discovery of 7-Methylguanosine-Based Molecular Rotors.The Journal of organic chemistry · 2023Article
- Targeted Degradation of mRNA Decapping Enzyme DcpS by a VHL-Recruiting PROTAC.ACS chemical biology · 2022Article
- Study of Single Nucleotide Polymorphisms Associated with Breast Cancer Patients among Arab Ancestries.International journal of breast cancer · 2022Article
- Evaluation of carboxyfluorescein-labeled 7-methylguanine nucleotides as probes for studying cap-binding proteins by fluorescence anisotropy.Scientific reports · 2021Article
- Small molecule targeting of RNA structures in neurological disorders.Annals of the New York Academy of Sciences · 2020Review
- Synthesis of Trifluoromethylated Purine Ribonucleotides and Their Evaluation asThe Journal of organic chemistry · 2020Article
- Structure-based design and analysis of SuFEx chemical probes.RSC medicinal chemistry · 2020Review
- Drug Screening and Drug Repositioning as Promising Therapeutic Approaches for Spinal Muscular Atrophy Treatment.Frontiers in pharmacology · 2020Review
- Neurotheranostics as personalized medicines.Advanced drug delivery reviews · 2019Review
- N1-Propargylguanosine Modified mRNA Cap Analogs: Synthesis, Reactivity, and Applications to the Study of Cap-Binding Proteins.Molecules (Basel, Switzerland) · 2019Article
- Targeting mRNA Decapping in AML.Cancer cell · 2018Article
- In Silico Studies in Drug Research Against Neurodegenerative Diseases.Current neuropharmacology · 2018Review
- mRNA cap analogues substituted in the tetraphosphate chain with CX2: identification of O-to-CCl2 as the first bridging modification that confers resistance to decapping without impairing translation.Nucleic acids research · 2017Article
- The effects of C5-substituted 2,4-diaminoquinazolines on selected transcript expression in spinal muscular atrophy cells.PloS one · 2017Article
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 2 countries.
Funding
Abstract
Spinal muscular atrophy (SMA) is caused by deletion or mutation of both copies of the SMN1 gene, which produces an essential protein known as SMN. The severity of SMA is modified by variable copy number of a second gene,SMN2, which produces an mRNA that is incorrectly spliced with deletion of the last exon. We described previously the discovery of potent C5-substituted quinazolines that increase SMN2 gene expression by 2-fold. Discovery of potent SMN2 promoter inducers relied on a cellular assay without knowledge of the molecular target. Using protein microarray scanning with a radiolabeled C5-substituted quinazoline probe, we identified the scavenger decapping enzyme, DcpS, as a potential binder. We show that the C5-substituted quinazolines potently inhibit DcpS decapping activity and that the potency of inhibition correlates with potency forSMN2 promoter induction. Binding of C5-substituted quinazolines to DcpS holds the enzyme in an open, catalytically incompetent conformation. DcpS is a nuclear shuttling protein that binds and hydrolyzes the m(7)GpppN mRNA cap structure and a modulator of RNA metabolism. Therefore DcpS represents a novel therapeutic target for modulating gene expression by a small molecule.
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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.