2. Academic Validation
  3. Targeting Enhancer of Zeste Homolog 2 for the Treatment of Hematological Malignancies and Solid Tumors: Candidate Structure-Activity Relationships Insights and Evolution Prospects

Targeting Enhancer of Zeste Homolog 2 for the Treatment of Hematological Malignancies and Solid Tumors: Candidate Structure-Activity Relationships Insights and Evolution Prospects

  • J Med Chem. 2022 May 26;65(10):7016-7043. doi: 10.1021/acs.jmedchem.2c00047.
Juan Xia 1,  Jingyi Li 2,  Lei Tian 2 3,  Xiaodong Ren 4,  Chang Liu 5,  Chengyuan Liang 2
Affiliations

Affiliations

  • 1 Laboratory of Hematologic Diseases, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, P. R. China.
  • 2 Faculty of Pharmacy, Shaanxi University of Science & Technology, Xi'an 710021, P. R. China.
  • 3 College of Bioresources Chemical and Materials Engineering, Shaanxi University of Science & Technology, Xi'an 710021, P. R. China.
  • 4 Medical College, Guizhou University, Guiyang 550025, P. R. China.
  • 5 Zhuhai Jinan Selenium Source Nanotechnology Co., Ltd., Zhuhai 519030, P. R. China.
PMID: 35531606 DOI: 10.1021/acs.jmedchem.2c00047
Abstract

Enhancer of zeste homolog 2 (EZH2) is a Histone Methyltransferase that can change the expression of downstream target genes by catalyzing the trimethylation of lysine 27 of histone H3 (H3K27me3). Studies have found that EZH2 is highly expressed in a variety of tumor tissues and is closely related to the occurrence, development, invasion, and metastasis of tumors; therefore, EZH2 is becoming a new molecular target in antitumor therapy. Tazemetostat (EPZ-6438) was approved in 2020 as the first inhibitor targeting catalytic EZH2 for the treatment of epithelioid sarcoma. In addition, a variety of EZH2 inhibitors are being investigated in basic and clinical research for the treatment of tumors, and encouraging results have been obtained. This article systematically reviews the research progress on EZH2 inhibitors and proteolysis targeting chimera (PROTAC)-based EZH2 degradation agents with a focus on their design strategies, structure-activity relationships (SARs), and safety and clinical manifestations.

Figures
Products