Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10595502 | Bioorganic & Medicinal Chemistry Letters | 2013 | 6 Pages |
Abstract
To reduce the pro-angiogenic effects of sEH inhibition, a structure-activity relationship (SAR) study was performed by incorporating structural features of the anti-angiogenic multi-kinase inhibitor sorafenib into soluble epoxide hydrolase (sEH) inhibitors. The structural modifications of this series of molecules enabled the altering of selectivity towards the pro-angiogenic kinases C-RAF and vascular endothelial growth factor receptor-2 (VEGFR-2), while retaining their sEH inhibition. As a result, sEH inhibitors with greater potency against C-RAF and VEGFR-2 were obtained. Compound 4 (t-CUPM) possesses inhibition potency higher than sorafenib towards sEH but similar against C-RAF and VEGFR-2. Compound 7 (t-CUCB) selectively inhibits sEH, while inhibiting HUVEC cell proliferation, a potential anti-angiogenic property, without liver cancer cell cytotoxicity. The data presented suggest a potential rational approach to control the angiogenic responses stemming from sEH inhibition.
Keywords
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Sung Hee Hwang, Aaron T. Wecksler, Guodong Zhang, Christophe Morisseau, Long V. Nguyen, Samuel H. Fu, Bruce D. Hammock,