ArticleACS chemical neuroscience2012
Identification of a Maleimide-Based Glycogen Synthase Kinase-3 (GSK-3) Inhibitor, BIP-135, that Prolongs the Median Survival Time of Δ7 SMA KO Mouse Model of Spinal Muscular Atrophy.
Article in ACS chemical neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 33 citations in OpenAlex.
- Evaluation of the orally bioavailable 4-phenylbutyrate-tethered trichostatin A analogue AR42 in models of spinal muscular atrophy.Scientific reports · 2023Article
- A combinatorial approach increases SMN level in SMA model mice.Human molecular genetics · 2022Article
- GSK-3β, FYN, and DYRK1A: Master Regulators in Neurodegenerative Pathways.International journal of molecular sciences · 2021Review
- Impairment of the neurotrophic signaling hub B-Raf contributes to motoneuron degeneration in spinal muscular atrophy.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Self-oligomerization regulates stability of survival motor neuron protein isoforms by sequestering an SCFMolecular biology of the cell · 2018Article
- Axon outgrowth and neuronal differentiation defects after a-SMN and FL-SMN silencing in primary hippocampal cultures.PloS one · 2018Article
- Antisense Oligonucleotide-Based Therapy for Neuromuscular Disease.Molecules (Basel, Switzerland) · 2017Review
- 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
- Chronic Treatment with the AMPK Agonist AICAR Prevents Skeletal Muscle Pathology but Fails to Improve Clinical Outcome in a Mouse Model of Severe Spinal Muscular Atrophy.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2016Article
- Spinal muscular atrophy: an update on therapeutic progress.Biochimica et biophysica acta · 2013Review
- Enhancement of SMN protein levels in a mouse model of spinal muscular atrophy using novel drug-like compounds.EMBO molecular medicine · 2013Article
- Characterization of maleimide-based glycogen synthase kinase-3 (GSK-3) inhibitors as stimulators of steroidogenesis.Journal of medicinal chemistry · 2013Article
- Target- and mechanism-based therapeutics for neurodegenerative diseases: strength in numbers.Journal of medicinal chemistry · 2013Review
- Article
- SMN-inducing compounds for the treatment of spinal muscular atrophy.Future medicinal chemistry · 2012Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The discovery of upregulated glycogen synthase kinase-3 (GSK-3) in various pathological conditions has led to the development of a host of chemically diverse small molecule GSK-3 inhibitors, such as BIP-135. GSK-3 inhibition emerged as an alternative therapeutic target for treating spinal muscular atrophy (SMA) when a number of GSK-3 inhibitors were shown to elevate survival motor neuron (SMN) levels in vitro and to rescue motor neurons when their intrinsic SMN level was diminished by SMN-specific short hairpin RNA (shRNA). Despite their cellular potency, the in vivo efficacy of GSK-3 inhibitors has yet to be evaluated in an animal model of SMA. Herein, we disclose that a potent and reasonably selective GSK-3 inhibitor, namely BIP-135, was tested in a transgenic Δ7 SMA KO mouse model of SMA, and found to prolong the median survival of these animals. In addition, this compound was shown to elevate the SMN protein level in SMA patient-derived fibroblast cells as determined by western blot, and was neuroprotective in a cell-based, SMA-related model of oxidative stress-induced neurodegeneration.
Identifiers
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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.