Inhibition of XPO-1 Mediated Nuclear Export through the Michael-Acceptor Character of Chalcones.

ABSTRACT: The nuclear export receptor exportin-1 (XPO1, CRM1) mediates the nuclear export of proteins that contain a leucine-rich nuclear export signal (NES) towards the cytoplasm. XPO1 is considered a relevant target in different human diseases, particularly in hematological malignancies, tumor resistance, inflammation, neurodegeneration and viral infections. Thus, its pharmacological inhibition is of significant therapeutic interest. The best inhibitors described so far (leptomycin B and SINE compounds) interact with XPO1 through a covalent interaction with Cys528 located in the NES-binding cleft of XPO1. Based on the well-established feature of chalcone derivatives to react with thiol groups via hetero-Michael addition reactions, we have synthesized two series of chalcones. Their capacity to reac

SUBMITTER: Gargantilla M 

PROVIDER: S-EPMC8621101 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature