@article{a30074773ad64358a956df4464320f5e,
title = "Discovery of Small Molecules that Induce the Degradation of Huntingtin",
abstract = "Huntington's disease (HD) is an autosomal dominant neurodegenerative disorder caused by the aggregation of mutant huntingtin (mHtt), and removal of toxic mHtt is expected to be an effective therapeutic approach. We designed two small hybrid molecules (1 and 2) by linking a ligand for ubiquitin ligase (cellular inhibitor of apoptosis protein 1; cIAP1) with probes for mHtt aggregates, anticipating that these compounds would recruit cIAP1 to mHtt and induce selective degradation by the ubiquitin-proteasome system. The synthesized compounds reduced mHtt levels in HD patient fibroblasts and appear to be promising candidates for the development of a treatment for HD.",
keywords = "Huntington's disease, drug design, medicinal chemistry, protein degradation, small-molecule protein degraders",
author = "Shusuke Tomoshige and Sayaka Nomura and Kenji Ohgane and Yuichi Hashimoto and Minoru Ishikawa",
note = "Funding Information: The work described in this article was partially supported by Grants-in-Aid for Scientific Research from The Ministry of Education, Culture, Sports, Science and Technology, Japan, and the Japan Society for Promotion of Science. This work was also supported financially by Platform for Drug Discovery, Informatics, and Structural Life Science. We are grateful to Prof. Mikihiko Naito for helpful discussions. The following cells/DNA samples were obtained from the NIGMS Human Genetic Cell Repository at the Coriell Institute for Medical Research: GM04281, GM01187, GM07492 and CH00019. Publisher Copyright: {\textcopyright} 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim",
year = "2017",
month = sep,
day = "11",
doi = "10.1002/anie.201706529",
language = "English",
volume = "56",
pages = "11530--11533",
journal = "Angewandte Chemie - International Edition",
issn = "1433-7851",
publisher = "John Wiley and Sons Ltd",
number = "38",
}