The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Discovery of Risdiplam, a Selective Survival of Motor Neuron-2 ( SMN2 ) Gene Splicing Modifier for the Treatment of Spinal Muscular Atrophy (SMA)
Open accessAbstract
SMA is an inherited disease that leads to loss of motor function and ambulation and a reduced life expectancy. We have been working to develop orally administrated, systemically distributed small molecules to increase levels of functional SMN protein. Compound 2 was the first SMN2 splicing modifier tested in clinical trials in healthy volunteers and SMA patients. It was safe and well tolerated and increased SMN protein levels up to 2-fold in patients. Nevertheless, its development was stopped as a precautionary measure because retinal toxicity was observed in cynomolgus monkeys after chronic daily oral dosing (39 weeks) at exposures in excess of those investigated in patients. Herein, we describe the discovery of 1 (risdiplam, RG7916, RO7034067) that focused on thorough pharmacology, DMPK and safety characterization and optimization. This compound is undergoing pivotal clinical trials and is a promising medicine for the treatment of patients in all ages and stages with SMA.
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SMN2 splicing modifiers improve motor function and longevity in mice with spinal muscular atrophy
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Self-citationThe Neurobiology of Childhood Spinal Muscular Atrophy
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SMN2 splice modulators enhance U1–pre-mRNA association and rescue SMA mice
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CLASSIFICATION OF SPINAL MUSCULAR ATROPHIES
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Bush, J. A., Aikawa, H., Fuerst, R., Li, Y., Ursu, A., Meyer, S. M., Benhamou, R. I., Chen, J. L., Khan, T., Wagner-Griffin, S., et al. (2021) · Science Translational Medicine · doi:10.1126/scitranslmed.abd5991 · Cited by 77
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Metadata
- Authors
- Ratni, H., Ebeling, M., Baird, J., Bendels, S., Bylund, J., Chen, K. S., Denk, N., Feng, Z., Green, L., Guerard, M., Jablonski, P., Jacobsen, B., Khwaja, O., Kletzl, H., Ko, C.-P., Kustermann, S., Marquet, A., Metzger, F., Mueller, B., Naryshkin, N. A., Paushkin, S. V., Pinard, E., Poirier, A., Reutlinger, M., Weetall, M., Zeller, A., Zhao, X., & Mueller, L.
- Venue
- Journal of Medicinal Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2018-07-25
- Volume
- 61
- Issue
- 15
- Pages
- 6501-6517
- ISSN
- 0022-2623 (ISSN-L)
- 1520-4804
- OpenAlex
- W2883929619
- Cited by
- 537
- References
- 27
- Type
- other
- Language
- en
- Open access
- green
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- Ratni, H., Ebeling, M., Baird, J., Bendels, S., Bylund, J., Chen, K. S., Denk, N., Feng, Z., Green, L., Guerard, M., Jablonski, P., Jacobsen, B., Khwaja, O., Kletzl, H., Ko, C.-P., Kustermann, S., Marquet, A., Metzger, F., Mueller, B., . . . Mueller, L. (2018). Discovery of Risdiplam, a Selective Survival of Motor Neuron-2 ( SMN2 ) Gene Splicing Modifier for the Treatment of Spinal Muscular Atrophy (SMA). Journal of Medicinal Chemistry. https://doi.org/10.1021/acs.jmedchem.8b00741
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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