Eur J Med Chem 2021 Jan 24;210:112964. Epub 2020 Oct 24.
State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, East China University of Science and Technology, 130 Mei Long Road, Shanghai, 200237, China; College of Pharmacy and Chemistry, Dali University, 5 Xue Ren Road, Dali, Yunnan, 671000, China; Frontiers Science Center for Materiobiology and Dynamic Chemistry, East China University of Science and Technology, 130 Mei Long Road, Shanghai, 200237, China. Electronic address:
Ubiquitin-like protein neddylation is overactivated in various human cancers and correlates with disease progression, and targeting this pathway represents a valuable therapeutic strategy. Our previous work disclosed an antihypertensive agent, candesartan cilexetic (CDC), serves as a novel neddylation inhibitor for suppressing tumor growth by targeting Nedd8-activating enzyme (NAE). In this study, 42 benzimidazole derivatives were designed and synthesized based on lead compound CDC to improve the neddylation inhibition and anticancer efficacy. Read More