2. Academic Validation
  3. Medicinal chemistry strategies targeting PRMT5 for cancer therapy

Medicinal chemistry strategies targeting PRMT5 for cancer therapy

  • Eur J Med Chem. 2022 Dec 15:244:114842. doi: 10.1016/j.ejmech.2022.114842.
Siyu Fu 1,  Qinwen Zheng 1,  Dan Zhang 1,  Congcong Lin 2,  Liang Ouyang 1,  Jifa Zhang 3,  Lei Chen 4
Affiliations

Affiliations

  • 1 Department of Neurology, Joint Research Institution of Altitude Health, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
  • 2 Department of Medicinal Chemistry and Natural Medicine Chemistry, College of Pharmacy, Harbin Medical University, Harbin, 150081, China.
  • 3 Department of Neurology, Joint Research Institution of Altitude Health, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China; Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. Electronic address: [email protected].
  • 4 Department of Neurology, Joint Research Institution of Altitude Health, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. Electronic address: [email protected].
PMID: 36274274 DOI: 10.1016/j.ejmech.2022.114842
Abstract

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.

Keywords

Anticancer; Protein arginine methyltransferases 5 (PRMT5); Small-molecule inhibitors; Structure-activity relationships (SARs).

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