| Autor: |
Aubé, J., McDonald, P., Muma, N.A., Klus, N.J., Roy, A., Kapadia, K., Frankowski, K.J. |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| DOI: |
10.17615/p671-4051 |
| Popis: |
The aberrant protein–protein interaction between calmodulin and mutant huntingtin protein in Huntington’s disease patients has been found to contribute to Huntington’s disease progression. A high-throughput screen for small molecules capable of disrupting this interaction revealed a sultam series as potent small-molecule disruptors. Diversification of the sultam scaffold afforded a set of 24 analogs or further evaluation. Several structure–activity trends within the analog set were found, most notably a negligible effect of absolute stereochemistry and a strong beneficial correlation with electron-withdrawing aromatic substituents. The most promising analogs were profiled for off-target effects at relevant kinases and, ultimately, one candidate molecule was evaluated for neuroprotection in a neuronal cell model of Huntington’s disease. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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