Aberrations in the ubiquitin–proteasome system — which maintains cellular protein homeostasis — are implicated in tumour development and progression. Here, Hyer et al. report the identification of TAK-243, a first-in-class inhibitor of the ubiquitin-activating enzyme. In vitro, TAK-243 induced defective protein turnover and proteotoxic stress, impaired cell cycle progression and inhibited DNA repair, leading to cytotoxicity in a panel of human cancer cell lines. In mice bearing subcutaneous xenograft tumours, representing both solid and haematological cancers, intravenous TAK-243 treatment for 3 weeks induced a marked and robust antitumour effect.
References
Hyer, M. et al. A small-molecule inhibitor of the ubiquitin activating enzyme for cancer treatment. Nat. Med. 24, 186–193 (2018)
Rights and permissions
About this article
Cite this article
Crunkhorn, S. Targeting the ubiquitin pathway. Nat Rev Drug Discov 17, 166 (2018). https://doi.org/10.1038/nrd.2018.33
Published:
Issue Date:
DOI: https://doi.org/10.1038/nrd.2018.33