1449598-75-7Relevant academic research and scientific papers
SCREENING METHOD
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Paragraph 0086; 0083, (2017/09/08)
The invention discloses a screening method for the identification of new compounds for use in the treatment of cancer.
A PROCESS FOR THE PREPARATION OF 2-PYRAZOLO[1,5-A]PYRAZIN-2-YLPYRIDO[1,2-A]PYRIMIDIN-4-ONE
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Page/Page column 36, (2017/12/09)
The present invention relates to a process for the preparation of 2-pyrazolo[1,5-a]pyrazin-2-ylpyrido[1,2-a]pyrimidin-4-one derivatives useful as pharmaceutically active compounds.
Discovery and Optimization of Small Molecule Splicing Modifiers of Survival Motor Neuron 2 as a Treatment for Spinal Muscular Atrophy
Woll, Matthew G.,Qi, Hongyan,Turpoff, Anthony,Zhang, Nanjing,Zhang, Xiaoyan,Chen, Guangming,Li, Chunshi,Huang, Song,Yang, Tianle,Moon, Young-Choon,Lee, Chang-Sun,Choi, Soongyu,Almstead, Neil G.,Naryshkin, Nikolai A.,Dakka, Amal,Narasimhan, Jana,Gabbeta, Vijayalakshmi,Welch, Ellen,Zhao, Xin,Risher, Nicole,Sheedy, Josephine,Weetall, Marla,Karp, Gary M.
, p. 6070 - 6085 (2016/07/26)
The underlying cause of spinal muscular atrophy (SMA) is a deficiency of the survival motor neuron (SMN) protein. Starting from hits identified in a high-throughput screening campaign and through structure-activity relationship investigations, we have developed small molecules that potently shift the alternative splicing of the SMN2 exon 7, resulting in increased production of the full-length SMN mRNA and protein. Three novel chemical series, represented by compounds 9, 14, and 20, have been optimized to increase the level of SMN protein by >50% in SMA patient-derived fibroblasts at concentrations of 160 nM. Daily administration of these compounds to severe SMA Δ7 mice results in an increased production of SMN protein in disease-relevant tissues and a significant increase in median survival time in a dose-dependent manner. Our work supports the development of an orally administered small molecule for the treatment of patients with SMA.
Specific Correction of Alternative Survival Motor Neuron 2 Splicing by Small Molecules: Discovery of a Potential Novel Medicine to Treat Spinal Muscular Atrophy
Ratni, Hasane,Karp, Gary M.,Weetall, Marla,Naryshkin, Nikolai A.,Paushkin, Sergey V.,Chen, Karen S.,McCarthy, Kathleen D.,Qi, Hongyan,Turpoff, Anthony,Woll, Matthew G.,Zhang, Xiaoyan,Zhang, Nanjing,Yang, Tianle,Dakka, Amal,Vazirani, Priya,Zhao, Xin,Pinard, Emmanuel,Green, Luke,David-Pierson, Pascale,Tuerck, Dietrich,Poirier, Agnes,Muster, Wolfgang,Kirchner, Stephan,Mueller, Lutz,Gerlach, Irene,Metzger, Friedrich
, p. 6086 - 6100 (2016/07/26)
Spinal muscular atrophy (SMA) is the leading genetic cause of infant and toddler mortality, and there is currently no approved therapy available. SMA is caused by mutation or deletion of the survival motor neuron 1 (SMN1) gene. These mutations or deletion
SCREENING METHOD
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Page/Page column 16, (2015/03/13)
The invention discloses a screening method for the identification of new compounds for use in the treatment of cancer.
COMPOUNDS FOR TREATING SPINAL MUSCULAR ATROPHY
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Paragraph 001218, (2013/08/28)
Provided herein are compounds, compositions thereof and uses therewith for treating spinal muscular atrophy.
