Medicinal chemistry strategies targeting PRMT5 for cancer therapy

被引：31

作者：

Fu, Siyu

Zheng, Qinwen ^{[1
,2
]}

Zhang, Dan ^{[1
,2
]}

Lin, Congcong ^{[4
]}

Ouyang, Liang ^{[1
,2
]}

Zhang, Jifa ^{[1
,2
,3
]}

Chen, Lei ^{[1
,2
]}

机构：

[1] Sichuan Univ, West China Hosp, Joint Res Inst Altitude Hlth, Dept Neurol,State Key Lab Biotherapy,Natl Clin Res, Chengdu 610041, Sichuan, Peoples R China

[2] Sichuan Univ, West China Hosp, Canc Ctr, Chengdu 610041, Sichuan, Peoples R China

[3] Sichuan Univ, West China Hosp, Frontiers Sci Ctr Dis related Mol Network, Chengdu 610041, Sichuan, Peoples R China

[4] Harbin Med Univ, Coll Pharm, Dept Med Chem & Nat Med Chem, Harbin 150081, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2022年 / 244卷

基金：

中国国家自然科学基金;

关键词：

Protein arginine methyltransferases 5 (PRMT5); Small -molecule inhibitors; Structure -activity relationships (SARs); Anticancer; ARGININE METHYLTRANSFERASE 5; WD REPEAT PROTEIN; SYMMETRIC DIMETHYLATION; DRUG DISCOVERY; TUMOR-GROWTH; CELL-DEATH; METHYLATION; INHIBITOR; EXPRESSION; POTENT;

D O I：

10.1016/j.ejmech.2022.114842

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Protein arginine methyltransferases 5 (PRMT5), a therapeutic target whose main physiological function is mono -and symmetric dimethylation of arginine, has drawn significant attention from researchers in the field. PRMT5 has been reported to participate in many cellular functions including cell growth, migration, and development. Upregulation of PRMT5 occurs in different kinds of tumors and is strongly associated with poor prognosis. In recent years, several PRMT5 inhibitors have entered clinical trials for the treatment of various cancers, such as advanced or recurrent solid tumors with MTAP deletion. Herein, we reviewed the binding modes and structure -activity relationships of novel PRMT5 inhibitors and discussed prospects of PRMT5 inhibitors in cancer therapy, aiming to provide insights on drug development of PRMT5 inhibitors.

引用

页数：22

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