Discovery of SIRT7 Inhibitor as New Therapeutic Options Against Liver Cancer

• DOI: 10.3389/fcell.2021.813233
• Publication Date: 2022-01-31T06:35:08Z
• Authors: Chen Zhang; Yaqi Li; Bohao Liu; Chao Ning; Yimin Li; Ying Wang; Zhuan Li
• Keywords: Cancer Therapy

Optimal therapeutic strategies for liver cancer patients remain challenging due to the high recurrence rate after surgical resection and chemotherapy resistance. Emerging evidence has shown that epigenetic factor SIRT7 is involved in various aspects of biology, while inactive reverses human phenotype suppresses tumor growth. In present study, we predicted structure by using fold recognition (or threading) method performed structure-based virtual screening develop specific inhibitor docking 939319 structurally diverse compounds with SIRT proteins. Compounds affinities but low other proteins were chosen as candidates inhibitor. Our leading 2800Z 40569Z showed strong interaction protein, specifically inhibited deacetylation activity vitro. results also revealed ARG-120, TRP-126, HIS-187 critical sites responsible small molecules. Mutations aforementioned significantly abolished inhibitory effects SIRT7. addition, vivo data indicated able induce apoptosis increase chemosensitivity sorafenib cancer. findings demonstrated targeting may offer novel options management, value chemical probes study biological functions well starting leads development new against