| Literature DB >> 15555999 |
Mitchell R Lunn1, David E Root, Allison M Martino, Stephen P Flaherty, Brian P Kelley, Daniel D Coovert, Arthur H Burghes, Nguyen Thi Man, Glenn E Morris, Jianhua Zhou, Elliot J Androphy, Charlotte J Sumner, Brent R Stockwell.
Abstract
Most patients with the pediatric neurodegenerative disease spinal muscular atrophy have a homozygous deletion of the survival motor neuron 1 (SMN1) gene, but retain one or more copies of the closely related SMN2 gene. The SMN2 gene encodes the same protein (SMN) but produces it at a low efficiency compared with the SMN1 gene. We performed a high-throughput screen of approximately 47,000 compounds to identify those that increase production of an SMN2-luciferase reporter protein, but not an SMN1-luciferase reporter protein. Indoprofen, a nonsteroidal anti-inflammatory drug (NSAID) and cyclooxygenase (COX) inhibitor, selectively increased SMN2-luciferase reporter protein and endogenous SMN protein and caused a 5-fold increase in the number of nuclear gems in fibroblasts from SMA patients. No other NSAIDs or COX inhibitors tested exhibited this activity.Entities:
Mesh：
Substances：
Year: 2004 PMID： 15555999 PMCID： PMC3160629 DOI： 10.1016/j.chembiol.2004.08.024
Source DB: PubMed Journal: Chem Biol ISSN： 1074-5521