GSK-J4: An H3K27 histone demethylase inhibitor, as a potential anti-cancer agent

Abstract

Aberrant epigenetic modifications are emerging as potent drivers of tumor initiation and progression. The deregulation of H3K27me3 marks has shown to play an important role in cancer progression in several cancers. The H3K27me3 mark is associated with gene silencing. The reversible nature of these epigenetic aberrations makes them an important target for treating cancer. GSK-J4 is a histone demethylase inhibitor that inhibits the JMJD3/UTX enzyme, which results in the upregulation of H3K27me3 levels. In this review, the anti-cancer properties of GSK-J4 have been summarized, the various molecular pathways targeted, in-vivo studies, and drug combination studies in different cancer models. GSK-J4 targeted pathways like apoptosis, cell cycle, invasion, migration, DNA damage repair, metabolism, oxidative stress, stemness, etc. GSK-J4 is a promising candidate alone and in combination with other conventional anti-cancer drugs against different cancer types.

Keywords: GSK-J4; In-vivo studies; cancer; combinatorial studies; histone modifications.