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Discovery and identification of a novel small molecule BCL-2 inhibitor that binds to the BH4 domain

Acta Pharmacol Sin. 2022-08; 
Jing-Yi Zhou, Rui-Rui Yang, Jie Chang, Jia Song, Zi-Sheng Fan, Ying-Hui Zhang, Cheng-Hao Lu, Hua-Liang Jiang, Ming-Yue Zheng, Su-Lin Zhang
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Catalog Antibody … The clarified cell lysates were immunoprecipitated with Protein A/G MagBeads (GenScript, L00277) combined with a c-Myc antibody (Cell Signaling Technology, 18583) overnight at 4 C… Get A Quote

摘要

The B-cell lymphoma 2 (BCL-2) protein family plays a pivotal role in regulating the apoptosis process. BCL-2, as an antiapoptotic protein in this family, mediates apoptosis resistance and is an ideal target for cell death strategies in cancer therapy. Traditional treatment modalities target BCL-2 by occupying the hydrophobic pocket formed by BCL-2 homology (BH) domains 1-3, while in recent years, the BH4 domain of BCL-2 has also been considered an attractive novel target. Herein, we describe the discovery and identification of DC-B01, a novel BCL-2 inhibitor targeting the BH4 domain, through virtual screening combined with biophysical and biochemical methods. Our results from surface plasmon resonance and cellu... More

关键词

BH4 domain, Bcl-2, antitumor, apoptosis, virtual screening