ArticleHuman molecular genetics2010
Effects of 2,4-diaminoquinazoline derivatives on SMN expression and phenotype in a mouse model for spinal muscular atrophy.
Article in Human molecular genetics, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02831296 (Prospective Evaluation of Infants With Spinal Muscular Atrophy), which is not on this map. Cited by 63 papers, 2 of them syntheses 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.
Prospective Evaluation of Infants With Spinal Muscular Atrophy: SPOT SMA
Who cites it
63 citing papers in PubMed, 2 syntheses or guidelines pooled it, 119 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
- Prenatal SMN-dependent defects in translation uncover reversible primary cilia phenotypes in spinal muscular atrophy.JCI insight · 2025Article
- 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
- Evaluation of the orally bioavailable 4-phenylbutyrate-tethered trichostatin A analogue AR42 in models of spinal muscular atrophy.Scientific reports · 2023Article
- Central synaptopathy is the most conserved feature of motor circuit pathology across spinal muscular atrophy mouse models.iScience · 2021Article
- Targeting the 5' untranslated region ofMolecular therapy. Nucleic acids · 2021Article
- Simultaneous Control of Endogenous and User-Defined Genetic Pathways Using Unique ecDHFR Pharmacological Chaperones.Cell chemical biology · 2020Article
- ZPR1 prevents R-loop accumulation, upregulates SMN2 expression and rescues spinal muscular atrophy.Brain : a journal of neurology · 2020Article
- Early skeletal muscle pathology and disease progress in the dyScientific reports · 2019Article
- Emerging therapies and challenges in spinal muscular atrophy.Annals of neurology · 2017Review
- 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
- Molecular Mechanisms of Neurodegeneration in Spinal Muscular Atrophy.Journal of experimental neuroscience · 2016Review
- Genetic inhibition of JNK3 ameliorates spinal muscular atrophy.Human molecular genetics · 2015Article
- Systemic, postsymptomatic antisense oligonucleotide rescues motor unit maturation delay in a new mouse model for type II/III spinal muscular atrophy.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- The effect of the DcpS inhibitor D156844 on the protective action of follistatin in mice with spinal muscular atrophy.Neuromuscular disorders : NMD · 2015Article
3 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
14 authors at 4 institutions in 3 countries.
Funding
Abstract
Proximal spinal muscular atrophy (SMA), one of the most common genetic causes of infant death, results from the selective loss of motor neurons in the spinal cord. SMA is a consequence of low levels of survival motor neuron (SMN) protein. In humans, the SMN gene is duplicated; SMA results from the loss of SMN1 but SMN2 remains intact. SMA severity is related to the copy number of SMN2. Compounds which increase the expression of SMN2 could, therefore, be potential therapeutics for SMA. Ultrahigh-throughput screening recently identified substituted quinazolines as potent SMN2 inducers. A series of C5-quinazoline derivatives were tested for their ability to increase SMN expression in vivo. Oral administration of three compounds (D152344, D153249 and D156844) to neonatal mice resulted in a dose-dependent increase in Smn promoter activity in the central nervous system. We then examined the effect of these compounds on the progression of disease in SMN lacking exon 7 (SMNDelta7) SMA mice. Oral administration of D156844 significantly increased the mean lifespan of SMNDelta7 SMA mice by approximately 21-30% when given prior to motor neuron loss. In summary, the C5-quinazoline derivative D156844 increases SMN expression in neonatal mouse neural tissues, delays motor neuron loss at PND11 and ameliorates the motor phenotype of SMNDelta7 SMA mice.
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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.