Inhibition of Jumonji demethylases reprograms severe dilated cardiomyopathy and prolongs survival

Abstract

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Jumonji Histone Demethylase Inhibitor JIB-04 as a Broad-Spectrum Antifungal Agent

“…Jumonji histone demethylase plays an important role in the regulation and expression of genes, and several inhibitors have entered clinical trials. 12,25,26 JIB-04 was reported as an inhibitor of the Jumonji subfamily of human HDMs. 10 To evaluate the inhibition of JIB-04 on Jumonji enzyme activity in fungal cells, the total nucleoprotein of C. neoformans H99 was extracted and JMJD3 (H3K27me3) and JARID (H3K4me3) were used as substrates for the inhibition assay of fungal HDMs.…”

Epigenetic modification mechanism of histone demethylase KDM1A in regulating cardiomyocyte apoptosis after myocardial ischemia-reperfusion injury

“…H3K4me3 is closely related to several heart-related pathologies, such as hypertrophic/dilated cardiomyopathy ( Raveendran et al, 2020 ; Tran et al, 2022 ), and is associated with the conversion of the induced cardiomyocytes ( Liu et al, 2016 ). Additionally, dexmedetomidine precondition in lung tissues alleviated I/R-induced lung injury via modulating H3K4me3 modification on the KGF-2 promoter ( Hong et al, 2021 ).…”

Recent Advances with KDM4 Inhibitors and Potential Applications

“…While the functions of KDM4 in virus infection are unknown, a recent study has shown that JIB-04 has broad-spectrum antiviral activity and inhibits SARS-CoV-2 replication and coronavirus pathogenesis, indicating that KDM4 inhibition may have the potential to suppress infectious diseases. In a transgenic dilated cardiomyopathy mouse model, JIB-04 reduces heart size and prolongs mouse survival . Importantly, JIB-04 has no negative effect on healthy hearts .…”

“…In a transgenic dilated cardiomyopathy mouse model, JIB-04 reduces heart size and prolongs mouse survival. 153 Importantly, JIB-04 has no negative effect on healthy hearts. 154 Thus, KDM4 inhibitors might be suitable to treat cardiovascular diseases.…”