Design, Synthesis, and Characterization of Dichlorobiphenyl-Derived Inhibitors of the Proprotein Convertase Furin.

ABSTRACT: The proprotein convertase (PC) furin emerged as promising drug target for the treatment of numerous infectious diseases, cancer and cystic fibrosis. A recently described nonpeptidic lead structure served as template to develop a new series of PC inhibitors containing a dichlorobiphenyl-derived core segment decorated with a left and right inhibitor arm. The compounds were tested for their inhibitory potency against furin and the structurally related PC7. The most potent compounds inhibited furin with K_i values <5 nM, whereas most of them were significantly weaker inhibitors of PC7. Only for one compound, a significant potency with a K_i value of 7.3 nM against PC7 was found. Furthermore, crystal structures of six inhibitors in complex with furin were deter

SUBMITTER: Lange RW 

PROVIDER: S-EPMC12703725 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature