TY  - JOUR
AU  - Wang Yu-zhe
AU  - Liu Xiao
AU  - Way George
AU  - Madarha Vipul
AU  - Zhou Qing-tong
AU  - Yang De-hua
AU  - Liao Jia-yu
AU  - Wang Ming-wei
PY  - 2020
TI  - An in vitro Förster resonance energy transfer-based high-throughput screening assay identifies inhibitors of SUMOylation E2 Ubc9
JF  - Acta Pharmacologica Sinica; Vol 41, No 11 (November 2020): Acta Pharmacologica Sinica
Y2  - 2020
KW  - 
N2  - SUMOylation is one of the posttranslational modifications that mediate cellular activities such as transcription, DNA repair, and signal transduction and is involved in the cell cycle. However, only a limited number of small molecule inhibitors have been identified to study its role in cellular processes. Here, we report a Förster resonance energy transfer (FRET) high-throughput screening assay based on the interaction between E2 Ubc9 and E3 PIAS1. Of the 3200 compounds screened, 34 (1.1%) showed higher than 50% inhibition and 4 displayed dose–response inhibitory effects. By combining this method with a label-free surface plasmon resonance (SPR) assay, false positives were excluded leading to discovering WNN0605-F008 and WNN1062-D002 that bound to Ubc9 with KD values of 1.93 ± 0.62 and 5.24 ± 3.73 μM, respectively. We examined the effect of the two compounds on SUMO2-mediated SUMOylation of RanGAP1, only WNN0605-F008 significantly inhibited RanGAP1 SUMOylation, whereas WNN1062-D002 did not show any inhibition. These compounds, with novel chemical scaffolds, may serve as the initial material for developing new SUMOylation inhibitors.
UR  - http://www.chinaphar.com/article/view/10229