dc.contributor.author | Klus, Nicholas J. | |
dc.contributor.author | Kapadia, Khushboo | |
dc.contributor.author | McDonald, Peter | |
dc.contributor.author | Roy, Anuradha | |
dc.contributor.author | Frankowski, Kevin J. | |
dc.contributor.author | Muma, Nancy A. | |
dc.contributor.author | Aubé, Jeffrey | |
dc.date.accessioned | 2022-02-01T16:21:24Z | |
dc.date.available | 2022-02-01T16:21:24Z | |
dc.date.issued | 2020-06-12 | |
dc.identifier.citation | Klus, N.J., Kapadia, K., McDonald, P. et al. Discovery of sultam-containing small-molecule disruptors of the huntingtin–calmodulin protein–protein interaction. Med Chem Res 29, 1187–1198 (2020). https://doi.org/10.1007/s00044-020-02583-8 | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/32487 | |
dc.description.abstract | 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. | en_US |
dc.publisher | Springer | en_US |
dc.rights | Copyright © 2020, Springer Science Business Media, LLC, part of Springer Nature. | en_US |
dc.subject | Huntington’s disease | en_US |
dc.subject | High-throughput screening | en_US |
dc.subject | Neurodegeneration | en_US |
dc.subject | Structure–activity relationship studies | en_US |
dc.title | Discovery of sultam-containing small-molecule disruptors of the huntingtin–calmodulin protein–protein interaction | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Kapadia, Khushboo | |
kusw.kuauthor | McDonald, Peter | |
kusw.kuauthor | Roy, Anuradha | |
kusw.kuauthor | Muma, Nancy A. | |
kusw.kudepartment | Pharmacology and Toxicology | en_US |
kusw.kudepartment | High-Throughput Screening Laboratory | en_US |
dc.identifier.doi | 10.1007/s00044-020-02583-8 | en_US |
kusw.oaversion | Scholarly/refereed, author accepted manuscript | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC7906539 | en_US |
dc.rights.accessrights | openAccess | en_US |