4.7 Article

Design, synthesis and biological evaluation of 2-aminopyridine derivatives as USP7 inhibitors

期刊

BIOORGANIC CHEMISTRY
卷 129, 期 -, 页码 -

出版社

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bioorg.2022.106128

关键词

Aminopyridine; USP7 inhibitors; Suzuki coupling reaction; Colorectal carcinoma; MDM2; P53 and p21

资金

  1. Natural Science Interdisciplinary Research Program of Hebei University [DXK201903]
  2. Science and Technology Commission of Shanghai Municipality [21ZR1474700, 19XD1404700]
  3. Youth Innovation Promotion Association of CAS [2022279]

向作者/读者索取更多资源

A series of novel 2-aminopyridine derivatives were synthesized and evaluated for their USP7 inhibitory activities. Compounds 7 and 21 showed significant binding interactions with USP7 according to surface plasmon resonance binding assay.
A series of novel 2-aminopyridine derivatives 1-26 have been designed and synthesized by structural modifications on a lead USP7 inhibitor, GNE6640. All the compounds were evaluated for their USP7 inhibitory activities. The results showed that most of the compounds have good USP7 inhibitory activities at the concentration of 50 mu M. Among them, compounds 7, 14 and 21 are the most potential ones from each category with the IC50 values of 7.6 +/- 0.1 mu M, 17.0 +/- 0.2 mu M and 11.6 +/- 0.5 mu M, respectively. Compounds 7 and 21 expressed significant binding interactions with USP7 by surface plasmon resonance (SPR)-based binding assay, but both of them presented moderate antiproliferative activities against HCT116 cells. They could effectively promote MDM2 degradation, p53 stabilization and p21 gene expression in the western blot analysis.

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