| Residential College | false |
| Status | 已發表Published |
| Rational design of a sensitivity-enhanced tracer for discovering efficient APC–Asef inhibitors | |
Zhong, Jie1,2,3; Guo, Yuegui4; Lu, Shaoyong2; Song, Kun2; Wang, Ying2; Feng, Li3; Zheng, Zhen3; Zhang, Qiufen3; Wei, Jiacheng2; Sang, Peng5; Shi, Yan5; Cai, Jianfeng5; Chen, Guoqiang6; Liu, Chen-Ying4 ; Yang, Xiuyan2,7; Zhang, Jian1,2,3,8
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| 2022-08-24 | |
| Source Publication | Nature Communications
 |
| ISSN | 2041-1723 |
| Volume | 13Issue:1Pages:4961 |
| Abstract | The adenomatous polyposis coli (APC)–Rho guanine nucleotide exchange factor 4 (Asef) protein–protein interaction (PPI) is essential for colorectal cancer metastasis, making it a promising drug target. Herein, we obtain a sensitivity-enhanced tracer (tracer 7) with a high binding affinity (K = 0.078 μM) and wide signal dynamic range (span = 251 mp). By using tracer 7 in fluorescence-polarization assays for APC–Asef inhibitor screening, we discover a best-in-class inhibitor, MAI-516, with an IC of 0.041 ± 0.004 μM and a conjugated transcriptional transactivating sequence for generating cell-permeable MAIT-516. MAIT-516 inhibits CRC cell migration by specifically hindering the APC–Asef PPI. Furthermore, MAIT-516 exhibits no cytotoxic effects on normal intestinal epithelial cell and colorectal cancer cell growth. Overall, we develop a sensitivity-enhanced tracer for fluorescence polarization assays, which is used for the precise quantification of high-activity APC–Asef inhibitors, thereby providing insight into PPI drug development. |
| DOI | 10.1038/s41467-022-32612-6 |
| URL | View the original |
| Indexed By | SCIE |
| Language | 英語English |
| WOS Research Area | Science & Technology - Other Topics |
| WOS Subject | Multidisciplinary Sciences |
| WOS ID | WOS:000844555300006 |
| Scopus ID | 2-s2.0-85136492156 |
| Fulltext Access | |
| Citation statistics | |
| Document Type | Journal article |
| Collection | THE STATE KEY LABORATORY OF QUALITY RESEARCH IN CHINESE MEDICINE (UNIVERSITY OF MACAU) Institute of Chinese Medical Sciences |
| Co-First Author | Zhong, Jie; Guo, Yuegui |
| Corresponding Author | Liu, Chen-Ying; Yang, Xiuyan; Zhang, Jian |
| Affiliation | 1.State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China 2.Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, Shanghai Jiao Tong University School of Medicine, Shanghai, China 3.Medicinal Chemistry and Bioinformatics Center, Shanghai Jiao Tong University School of Medicine, Shanghai, China 4.Department of Colorectal and Anal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China 5.Department of Chemistry, University of South Florida, Tampa, FL, USA 6.Research Unit of Stress and Cancer, Chinese Academy of Medical Sciences, Shanghai, China 7.State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Macau, China 8.School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, China |
| Corresponding Author Affilication | Institute of Chinese Medical Sciences |
| Recommended Citation GB/T 7714 | Zhong, Jie,Guo, Yuegui,Lu, Shaoyong,et al. Rational design of a sensitivity-enhanced tracer for discovering efficient APC–Asef inhibitors[J]. Nature Communications, 2022, 13(1), 4961. |
| APA | Zhong, Jie., Guo, Yuegui., Lu, Shaoyong., Song, Kun., Wang, Ying., Feng, Li., Zheng, Zhen., Zhang, Qiufen., Wei, Jiacheng., Sang, Peng., Shi, Yan., Cai, Jianfeng., Chen, Guoqiang., Liu, Chen-Ying., Yang, Xiuyan., & Zhang, Jian (2022). Rational design of a sensitivity-enhanced tracer for discovering efficient APC–Asef inhibitors. Nature Communications, 13(1), 4961. |
| MLA | Zhong, Jie,et al."Rational design of a sensitivity-enhanced tracer for discovering efficient APC–Asef inhibitors".Nature Communications 13.1(2022):4961. |
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