G-quadruplex stabilization via small-molecules as a potential anti-cancer strategy

被引:74
作者
Awadasseid, Annoor [1 ,2 ,4 ]
Ma, Xudong [1 ,2 ]
Wu, Yanling [3 ]
Zhang, Wen [1 ,2 ]
机构
[1] Zhejiang Univ Technol, Coll Pharmaceut Sci, Lab Chem Biol & Mol Drug Design, 18 Chaowang Rd, Hangzhou 310014, Peoples R China
[2] Zhejiang Univ Technol, Inst Drug Dev & Chem Biol, Hangzhou 310014, Peoples R China
[3] Zhejiang Prov Ctr Dis Control & Prevent, Virus Inspect Dept, Lab Mol Immunol, 630 Xincheng Rd, Hangzhou 310051, Peoples R China
[4] Univ Kordofan, Dept Biochem & Food Sci, Al Ubayyid 51111, Sudan
基金
中国国家自然科学基金;
关键词
G-quadruplexes; G-quadruplex stabilization; Small-molecule drugs; Cancer therapy; Cancer; DNA SECONDARY STRUCTURES; C-MYC PROMOTER; SYNTHETIC LETHALITY; GENOME INSTABILITY; CANCER; TELOMERE; TARGET; INHIBITION; STABILITY; LIGANDS;
D O I
10.1016/j.biopha.2021.111550
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
G-quadruplexes (G4) are secondary four-stranded DNA helical structures consisting of guanine-rich nucleic acids, which can be formed in the promoter regions of several genes under proper conditions. Several cancer cells have been shown to emerge from genomic changes in the expression of crucial growth-regulating genes that allow cells to develop and begin to propagate in an undifferentiated state. Recent attempts have focused on producing treatments targeted at particular protein products of genes that are abnormally expressed. Many of the proteins found are hard to target and considered undruggable due to structural challenges, protein overexpression, or mutations that affect treatment resistance. The utilization of small molecules that stabilize secondary DNA structures existing in several possible oncogenes' promoters and modulate their transcription is a new strategy that avoids some of these problems. In this review, we outline the function of G-quadruplex stabilization in cancer by small-molecules with the aim to improve cancer therapy.
引用
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页数:9
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