A patent review of EZH2 inhibitors from 2017 and beyond

Introduction: EZH2 is an important epigenetic regulator that forms the PRC2 complex with SUZ12, EED and RbAp46/48. As the key catalytic subunit of PRC2, EZH2 regulates the trimethylation of histone H3K27, which in turn promotes chromatin condensation and represses the transcription of relevant target genes. EZH2 overexpression and mutations are strictly related to tumor proliferation, invasion and metastasis. Currently, a large number of highly specific EZH2 inhibitors have been developed and some have already been in clinical trials.

Areas covered: The aim of the present review is to provide an overview of the molecular mechanisms of EZH2 inhibitors and to highlight the research advances in the patent literature published from 2017 to date. A search of the literature and patents for EZH2 inhibitors and degraders was performed using the Web of Science, SCIFinder, WIPO, USPTO, EPO and CNIPA databases.

Expert opinion: In recent years, a great number of structurally diverse EZH2 inhibitors have been identified, including EZH2 reversible inhibitors, EZH2 irreversible inhibitors, EZH2-based dual inhibitors and EZH2 degraders. Despite the multiple challenges, EZH2 inhibitors offer promising potential for the treatment of various diseases, such as cancers.

Comments：

EZH2 inhibitors are an emerging class of drugs that target EZH2, an important epigenetic regulator that plays a critical role in tumorigenesis. EZH2 inhibitors work by blocking the catalytic activity of EZH2, leading to a decrease in histone H3K27 trimethylation and subsequent inhibition of cancer cell growth.

There are several types of EZH2 inhibitors, including reversible and irreversible inhibitors, dual inhibitors, and degraders. Reversible inhibitors bind to EZH2 reversibly, while irreversible inhibitors covalently bind to EZH2, resulting in permanent inhibition. Dual inhibitors target both EZH2 and other cancer-related proteins, such as BET bromodomain proteins, to achieve better therapeutic efficacy. EZH2 degraders, on the other hand, induce the degradation of EZH2 protein, leading to a more sustained and long-lasting inhibition of EZH2 activity.

Although EZH2 inhibitors have shown promising results in preclinical studies and clinical trials, there are still several challenges that need to be overcome, including drug resistance, off-target effects, and toxicity. Further research is needed to optimize the efficacy and safety of EZH2 inhibitors and to explore their potential applications in the treatment of various diseases.

Related Products

Cat.No.	Product Name	Information
S7128	Tazemetostat (EPZ-6438)	Tazemetostat (EPZ-6438, E7438) is a potent, and selective EZH2 inhibitor with Ki and IC50 of 2.5 nM and 11 nM in cell-free assays, exhibiting a 35-fold selectivity versus EZH1 and >4,500-fold selectivity relative to 14 other HMTs.

Related Targets

EZH1/2 Histone Methyltransferase