ArticleHuman molecular genetics2013
The DcpS inhibitor RG3039 improves motor function in SMA mice.
Article in Human molecular genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 2 of them syntheses that pooled it.
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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
39 citing papers in PubMed, 2 syntheses or guidelines pooled it, 69 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
- Decapping scavenger enzyme as a promising biomarker in diabetic foot ulcers: A need for cautious interpretation.World journal of diabetes · 2026Article
- The effect of coadministration of D156844 and AR42 (REC-2282) on the survival and motor phenotype of mice with spinal muscular atrophy.Scientific reports · 2025Article
- Effect of the mRNA decapping enzyme scavenger (DCPS) inhibitor RG3039 on glioblastoma.Journal of translational medicine · 2024Article
- Evaluation of the orally bioavailable 4-phenylbutyrate-tethered trichostatin A analogue AR42 in models of spinal muscular atrophy.Scientific reports · 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
- Targeting the 5' untranslated region ofMolecular therapy. Nucleic acids · 2021Article
- Synthesis of Trifluoromethylated Purine Ribonucleotides and Their Evaluation asThe Journal of organic chemistry · 2020Article
- Lowering EphA4 Does Not Ameliorate Disease in a Mouse Model for Severe Spinal Muscular Atrophy.Frontiers in neuroscience · 2019Article
- Genome-wide CRISPR-Cas9 Screen Identifies Leukemia-Specific Dependence on a Pre-mRNA Metabolic Pathway Regulated by DCPS.Cancer cell · 2018Article
- Antisense Oligonucleotides: Translation from Mouse Models to Human Neurodegenerative Diseases.Neuron · 2017Review
- Discovery of a Small Molecule Probe That Post-Translationally Stabilizes the Survival Motor Neuron Protein for the Treatment of Spinal Muscular Atrophy.Journal of medicinal chemistry · 2017Article
- Article
- The effects of C5-substituted 2,4-diaminoquinazolines on selected transcript expression in spinal muscular atrophy cells.PloS one · 2017Article
- Small Molecules in Development for the Treatment of Spinal Muscular Atrophy.Journal of medicinal chemistry · 2016Review
- Protective effects of butyrate-based compounds on a mouse model for spinal muscular atrophy.Experimental neurology · 2016Article
- Developing therapies for spinal muscular atrophy.Annals of the New York Academy of Sciences · 2016Review
Corrections and comments
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Authors and funding
16 authors at 4 institutions in 1 country.
Funding
Abstract
Spinal muscular atrophy (SMA) is caused by mutations of the survival motor neuron 1 (SMN1) gene, retention of the survival motor neuron 2 (SMN2) gene and insufficient expression of full-length survival motor neuron (SMN) protein. Quinazolines increase SMN2 promoter activity and inhibit the ribonucleic acid scavenger enzyme DcpS. The quinazoline derivative RG3039 has advanced to early phase clinical trials. In preparation for efficacy studies in SMA patients, we investigated the effects of RG3039 in severe SMA mice. Here, we show that RG3039 distributed to central nervous system tissues where it robustly inhibited DcpS enzyme activity, but minimally activated SMN expression or the assembly of small nuclear ribonucleoproteins. Nonetheless, treated SMA mice showed a dose-dependent increase in survival, weight and motor function. This was associated with improved motor neuron somal and neuromuscular junction synaptic innervation and function and increased muscle size. RG3039 also enhanced survival of conditional SMA mice in which SMN had been genetically restored to motor neurons. As this systemically delivered drug may have therapeutic benefits that extend beyond motor neurons, it could act additively with SMN-restoring therapies delivered directly to the central nervous system such as antisense oligonucleotides or gene therapy.
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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.