Discovery of IHMT-337 as a potent irreversible EZH2 inhibitor targeting CDK4 transcription for malignancies.

ABSTRACT: Enhancer of zeste homolog 2 (EZH2), an enzymatic subunit of PRC2 complex, plays an important role in tumor development and progression through its catalytic and noncatalytic activities. Overexpression or gain-of-function mutations of EZH2 have been significantly associated with tumor cell proliferation of triple-negative breast cancer (TNBC) and diffuse large B-cell lymphoma (DLBCL). As a result, it has gained interest as a potential therapeutic target. The currently available EZH2 inhibitors, such as EPZ6438 and GSK126, are of benefit for clinical using or reached clinical trials. However, certain cancers are resistant to these enzymatic inhibitors due to its noncatalytic or transcriptional activity through modulating nonhistone proteins. Thus, it may be more effective to synergistically

SUBMITTER: Mei H 

PROVIDER: S-EPMC9841011 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature