Abstract | BACKGROUND: METHODS: In this study, we developed a virtual screening integrated affinity screening technology for target protein drug screening. A series of in vitro and in vivo experiments were used for drug activity verification. Multi-omics analysis and flow cytometry analysis were used to explore antitumor mechanisms. Comparative analysis of proteome and transcriptome combined with survival follow-up information of patients reveals the clinical therapeutic potential of screened drugs. RESULTS: We screened three compounds, nilotinib, ABT-737, and evacetrapib, that exhibited optimal binding with SOAT1. In particular, nilotinib displayed a high affinity for SOAT1 protein and significantly inhibited tumor activity both in vitro and in vivo. Multi-omics analysis and flow cytometry analysis indicated that SOAT1-targeting compounds reprogrammed the cholesterol metabolism in tumors and enhanced CD8+ T cells and neutrophils to suppress tumor growth. CONCLUSIONS: Taken together, we reported several high-affinity SOAT1 ligands and demonstrated their clinical potential in the precision therapy of liver cancer, and also reveal the potential antitumor mechanism of SOAT1-targeting compounds.
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Authors | Zhihua Wang, Miaomiao Wang, Mengxin Zhang, Kaikun Xu, Xinshuai Zhang, Yi Xie, Yiming Zhang, Cheng Chang, Xiaolu Li, Aihua Sun, Fuchu He |
Journal | BMC medicine
(BMC Med)
Vol. 20
Issue 1
Pg. 292
(08 09 2022)
ISSN: 1741-7015 [Electronic] England |
PMID | 35941608
(Publication Type: Journal Article)
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Copyright | © 2022. The Author(s). |
Chemical References |
- Cholesterol
- Sterol O-Acyltransferase
- sterol O-acyltransferase 1
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Topics |
- CD8-Positive T-Lymphocytes
- Carcinoma
- Cholesterol
(metabolism)
- Humans
- Sterol O-Acyltransferase
(chemistry, metabolism)
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