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ID: ALA2417363

Journal: Bioorg Med Chem Lett

Title: Identification of quinazolinyloxy biaryl urea as a new class of SUMO activating enzyme 1 inhibitors.

Authors: Kumar A, Ito A, Hirohama M, Yoshida M, Zhang KY.

Abstract: SUMO activating enzyme 1 (SUMO E1) is the first enzyme in sumoylation pathway and an important cancer drug target. However, only a few inhibitors were reported up to now that includes three natural products, semi-synthetic protein inhibitors and one AMP mimic. Here, we report the identification of quinazolinyloxy biaryl urea as a new class of SUMO E1 inhibitors. The most active compound of this class inhibited the in vitro sumoylation with an IC50 of 13.4 μM. This compound inhibits sumoylation by blocking the formation of SUMOE1-SUMO thioester intermediate. The biological activity of the most active compound is comparable to previously reported inhibitors with properties suitable for medicinal chemistry optimization for potency and druggability.

CiteXplore: 23920437

DOI: 10.1016/j.bmcl.2013.07.022