Be Aware of Aggregators in the Search for Potential Human ecto-5'-Nucleotidase Inhibitors.

ABSTRACT: Promiscuous inhibition due to aggregate formation has been recognized as a major concern in drug discovery campaigns. Here, we report some aggregators identified in a virtual screening (VS) protocol to search for inhibitors of human ecto-5'-nucleotidase (ecto-5'-NT/CD73), a promising target for several diseases and pathophysiological events, including cancer, inflammation and autoimmune diseases. Four compounds (A, B, C and D), selected from the ZINC-11 database, showed IC₅₀ values in the micromolar range, being at the same time computationally predicted as potential aggregators. To confirm if they inhibit human ecto-5'-NT via promiscuous mechanism, forming aggregates, enzymatic assays were done in the presence of 0.01% (

SUBMITTER: Viviani LG 

PROVIDER: S-EPMC6222861 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature