Oxa Analogues of Nexturastat A Demonstrate Improved HDAC6 Selectivity and Superior Antileukaemia Activity.

ABSTRACT: The acetylome is important for maintaining the homeostasis of cells. Abnormal changes can result in the pathogenesis of immunological or neurological diseases, and degeneration can promote the manifestation of cancer. In particular, pharmacological intervention in the acetylome with pan-histone deacetylase (HDAC) inhibitors is clinically validated. However, these drugs exhibit an undesirable risk-benefit profile due to severe side effects. Selective HDAC inhibitors might promote patient compliance and represent a valuable opportunity in personalised medicine. Therefore, we envisioned the development of HDAC6-selective inhibitors. During our lead structure identification, we demonstrated that an alkoxyurea-based connecting unit proves to be beneficial for HDAC6 selectivity and established t

SUBMITTER: Pflieger M 

PROVIDER: S-EPMC8251746 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature