H3k27 demethylase inhibitor. Oncotarget (2017) 8:62131–42.

H3k27 demethylase inhibitor 1B) , the HDAC inhibitor suberoylanilide hydroxamic acid (vorinostat) and the b romodomain and e xtra-t erminal (BET) family proteins inhibitor +JQ1 (Fig. It has been shown that H3K9me2 and H3K27me3 peptides bind with the same directionality to KDM7A, a dual-specificity H3K9/H3K27 demethylase from Caenorhabditis elegans 9 (Supplementary Fig. [Google Scholar] 81. Our work highlights how knowledge of normal processes in fetal development can Oct 21, 2021 · We have identified GSK-J4, a H3K27 demethylase inhibitor, as a potential agent for blocking latent HIV-1 reactivation in T cells. Laurens Kruidenier 1, Chun-wa Chung 2, Zhongjun Cheng 3, John Liddle 1, KaHing Che 4,5, A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. 1 B) , the HDAC inhibitor suberoylanilide hydroxamic acid (vorinostat) and the b romodomain and e xtra-t erminal (BET) family proteins inhibitor +JQ1 . , 2016; Xie et al. 2c and Supplementary Fig. doi: 10. Mar 17, 2020 · The antischistosomal potential of GSK-J4, an H3K27 demethylase inhibitor: insights from molecular modeling, transcriptomics and in vitro assays. Compared to the lead compound JIB-04 , derivative A4 had better water solubility, virulence factors inhibitory activity and in vivo antifungal potency. 18) highlights the shift in the divalent cation, as but lacks H3K27 demethylase activity, it provides an Jul 29, 2012 · A selective jumonji H3K27 demethylase inhibitor modulates the . Nature 488 , 404–408 (2012). Oncotarget. Show details Jun 23, 2023 · A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. (JMJD3 specific inhibitor) was used as an Jul 8, 2017 · Inhibitor of H3K27 demethylase JMJD3/UTX GSK-J4 is a potential therapeutic option for castration resistant prostate cancer Oncotarget . 2017;8:62131–62142. 1200/JCO. 6a, b). Oct 1, 2014 · A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. neoformans and C. 1 B) (16), the HDAC inhibitor suberoylanilide hydroxamic acid (vorinostat) (40) and the bromodomain and extra-terminal (BET) family proteins inhibitor +JQ1 (41) (Fig. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Background: GSKJ4, an H3K27 demethylase inhibitor, reportedly exhibits antitumor activity against specific cancers harboring genetic alterations in genes encoding chromatin modulators. , 2015; Hofstetter et al. Oct 15, 2017 · To test our hypothesis, GSKJ4, a potent selective jumonji H3K27 demethylase inhibitor was employed to evaluate the functions of the methylation of histone 3 lysine 27 on BCSCs in vitro. . Jul 26, 2017 · Persistent microglial activation is associated with the production and secretion of various pro-inflammatory genes, cytokines and chemokines, which may initiate or amplify neurodegenerative diseases. A novel synthetic histone 3 lysine 27 (H3K27) demethylase JMJD3 inhibitor, GSK-J4, was proven to exe … Jan 5, 2025 · Discovery of new fungal jumonji H3K27 demethylase inhibitors for the treatment of Cryptococcus neoformans and Candida auris infections Author links open overlay panel Xin Liu a 1 , Wang Li a 1 , Yang Liu b 1 , Xiaoqing Wang a , Qiao Shi a , Wanzhen Yang a , Jie Tu a , Yan Wang a , Chunquan Sheng a , Na Liu a The overlay of the peptide and inhibitor complexes (Fig. These results were confirmed by IC 50 measurements for the compounds that potently inhibited IFN-γ, comprising the H3K27 demethylase inhibitor GSK-J4 (Fig. 2012;488:404–408. Article CAS PubMed PubMed Central Google Scholar Feb 2, 2018 · These results were confirmed by IC 50 measurements for the compounds that potently inhibited IFN-γ, comprising the H3K27 demethylase inhibitor GSK-J4 (Fig. 2012;488:404–8. Vinogradova M. Feb 8, 2020 · Lysyl oxidase derived from M2-like macrophages also enhanced breast cancer cell migration, and this was suppressed by a H3K27 demethylase inhibitor. 7 × 10 −10; Fig. Sep 15, 2023 · GSK-J4 is a histone demethylase inhibitor that inhibits the JMJD3/UTX enzyme, which results in the upregulation of H3K27me3 levels. The present results suggest the mechanism of lysyl oxidase expression in M2-like macrophages as an aspect of epigenetics, particularly histone methylation. Oncotarget (2017) 8:62131–42. Some activity for the H3K4me3/2/1 demethylases Jarid1b and Jarid1c (IC50 values are 950 nM and 1. An inhibitor of KDM5 demethylases reduces survival of drug-tolerant cancer cells. Kruidenier L. Mar 12, 2017 · GSK-J4 is an ethyl ester derivative of the H3K27 demethylase inhibitor GSK-J1, and it has been used in various studies of the function of H3K27me3 histone demethylases (Kruidenier et al. Treatment of tumor cells with the H3K27 demethylase inhibitor GSKJ4 immediately before irradiation prevented the radiation-induced decrease in H3K27me3 and enhanced radiosensitivity. Article ADS CAS PubMed PubMed Central Google Scholar Feb 16, 2018 · These results were confirmed by IC 50 measurements for the compounds that potently inhibited IFN-γ, comprising the H3K27 demethylase inhibitor GSK-J4 (Fig. Dec 1, 2015 · The findings suggest that H3K27 methylation may have an inhibitory role in the maintenance of CSCs and that GSKJ4 may represent a novel class of C SC-targeting agents. We observed a range of sensitivity across the 31 neuroblastoma models included in May 10, 2023 · GSK-J4 is a histone demethylase inhibitor that inhibits the JMJD3/UTX enzyme, which results in the upregulation of H3K27me3 levels. May 1, 2023 · Therefore, demethylase inhibitors play an important role in the treatment of cancer. As determined by neutral comet analysis and γH2AX expression, this GSKJ4 treatment protocol inhibited the repair of radiation-induced DSBs. 76 μM, respectively). However, a genome-wide search for GSK-J4 Vinogradova M. The inactivation or deletion of methylase leads to the loss of the H3K27me3 mark in podocytes resulting in podocyte dedifferentiation and glomerular damage. 2017 Jul 8;8(37):62131-62142. 16_suppl. Among 31 epigenetic inhibitors, the H3K27 demethylase inhibitor GSK-J4 was found to reduce the production of collagens COL2A1 and COL10A1, structural components of cartilage and bone, respectively, and the glycosaminoglycan aggrecan in primary human bone marrow-derived mesenchymal stems cells (MSCs) undergoing chondrogenic differentiation (Fig Dec 1, 2022 · Cell Death Discovery - H3K27 tri-demethylase JMJD3 inhibits macrophage apoptosis by promoting ADORA2A in lipopolysaccharide-induced acute lung injury. Jul 29, 2012 · Our results resolve the ambiguity associated with the catalytic function of H3K27-specific JMJs in regulating disease-relevant inflammatory responses and provide encouragement for designing Aug 1, 2022 · Here, we review and summarise the pre-clinical evidence, both in vitro and in vivo, in support of the therapeutic potential of inhibiting H3K27-targeting demethylases, with a focus on the small-molecule inhibitor GSK-J4. KDM6A loss, like hypoxia, prevented H3K27 demethylation and blocked cellular differentiation. Thus, oxygen directly affects chromatin regulators to control cell fate. Nature 488 , 404–408 (2012) Article ADS CAS Google Scholar Aug 1, 2022 · Among 31 epigenetic inhibitors, the H3K27 demethylase inhibitor GSK-J4 was found to reduce the production of collagens COL2A1 and COL10A1, structural components of cartilage and bone, respectively, and the glycosaminoglycan aggrecan in primary human bone marrow-derived mesenchymal stems cells (MSCs) undergoing chondrogenic differentiation (Fig These results were confirmed by IC 50 measurements for the compounds that potently inhibited IFN-γ, comprising the H3K27 demethylase inhibitor GSK-J4 (Fig. Jan 5, 2025 · Compound A4 effectively inhibited the Jumonji H3K27 histone demethylase in C. Nat Chem Biol. , 2012; Liu et al. Restoring H3K27 methylation homeostasis in hypoxic cells reversed these effects. Inhibits UTX. DOI: 10. S2). 1038/nature11262. [ DOI ] [ PMC free article ] [ PubMed ] [ Google Scholar ] Oct 15, 2020 · Blocking the AFT4 stress response did not prevent suppression of TBXT and induction of cell death, but ectopic overexpression of TBXT increased viability, therefore implicating TBXT as a potential therapeutic target of H3K27 demethylase inhibitors in chordoma. 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. auris. Feb 25, 2021 · A selective jumonji H3K27 demethylase inhibitor modulates the proinflammatory macrophage response. Specifically, we exploited active site plasticity and targeted key substrate-binding features to identify the first series of selective H3K27 inhibitors. The present study shows that the H3K27me3 peptide binds to the H3K27-specific demethylase JMJD3 in the opposite orientation to KDM7A. α-KG/2-OG is a mandatory co-factor for demethylation by all JmjC-KDM, and most KDM inhibitors produce activity by broad-spectrum inhibition of α-KG/2-OG. e20035 Mar 15, 2019 · We found that the H3K27 histone demethylase KDM6A/UTX, but not its paralog KDM6B, is oxygen sensitive. 19100. 2085. 22 – 25 In contrast, research on KDM6 inhibitors has only recently been conducted in some cancers, such as prostate tumors, neuroblastoma, head and neck cancer, and colorectal Background/Aim: Global increase in the trimethylation of histone H3 at lysine 27 (H3K27me3) has been associated with the differentiation of normal stem cells and cancer cells, however, the role of H3K27me3 in the control of cancer stem cells (CSCs) remains poorly understood. Materials and methods: The effect of GSKJ4 on the viability as well as on the self-renewal and tumor-initiating capacity of CSCs derived from the A2780 human ovarian cancer cell line was examined. 2020 . proinflammatory macrophage response. The histone demethylase inhibitor GSK-J4 is a therapeutic target for the kidney fibrosis of Inhibitor of H3K27 demethylase JMJD3/UTX GSK-J4 is a potential therapeutic option for castration resistant prostate cancer. Inhibitor of H3K27 Demethylase JMJD3/UTX GSK-J4 is a Potential Therapeutic Option for Castration Resistant Prostate Cancer. , 2016). Materials May 10, 2023 · GSK-J4 is a histone demethylase inhibitor that inhibits the JMJD3/UTX enzyme, which results in the upregulation of H3K27me3 levels. 2016;12:531–538. Nature. 18632/oncotarget. 2024. We performed high-throughput drug screening of epigenetic-targeted therapies across a large and diverse tumor cell line panel and uncovered the hypersensitivity of neuroblastoma cells to GSK-J4, a small-molecule dual inhibitor of lysine 27 of histone 3 (H3K27) demethylases ubiquitously transcribed tetratricopeptide repeat, X chromosome (UTX Aug 8, 2012 · Our findings provide a strategy for the rational design and characterization of catalytic site inhibitors of JMJ enzymes. May 29, 2024 · Depletion of histone H3K27 demethylase exerts anti-tumor activity as a monotherapy and in combination therapy with ceralasertib in non-small cell lung carcinoma. Morozov VM, Li Y, Clowers MM, Ishov AM. BACKGROUND/AIM Global increase in the trimethylation of histone H3 at lysine 27 (H3K27me3) has been associated with the differentiation of normal stem cells and cancer cells, however, the role of H3K27me3 in the control of Mar 17, 2020 · @article{LoboSilva2020TheAP, title={The antischistosomal potential of GSK-J4, an H3K27 demethylase inhibitor: insights from molecular modeling, transcriptomics and in vitro assays}, author={J{\'e}ssica Lobo-Silva and Fernanda Janku Cabral and Murilo Sena Amaral and Patr{\'i}cia Aoki Miyasato and Rafaela Paula de Freitas and Adriana S. 1B) , the HDAC inhibitor suberoylanilide hydroxamic acid (vorinostat) and the b romodomain and e xtra-t erminal (BET) family proteins inhibitor +JQ1 . However, its potential as an anticancer agent against human cancers not associated with such genetic alterations, including non-small cell lung cancer (NSCLC MW 389. 4 Da, Purity >99%. 42. A novel synthetic histone 3 lysine 27 (H3K27) demethylase JMJD3 inhibitor, GSK-J4, was proven to exert immunosuppressive activities in macrophages. 1038/nchembio. As part of the continuing effort of the GDSC HTS (7, 18), we identified the histone H3K27 demethylase inhibitor GSK-J4 (16, 19) as having potent activity in neuroblastoma cell lines, among ~800 solid tumor cancer cell lines tested (P = 1. Aug 16, 2012 · We demonstrate that this inhibitor binds in a novel manner and reduces lipopolysaccharide-induced proinflammatory cytokine production by human primary macrophages, a process that depends on both JMJD3 and UTX. Jul 29, 2012 · Our results resolve the ambiguity associated with the catalytic function of H3K27-specific JMJs in regulating disease-relevant inflammatory responses and provide encouragement for designing Aug 1, 2022 · Here, we review and summarise the pre-clinical evidence, both in vitro and in vivo, in support of the therapeutic potential of inhibiting H3K27-targeting demethylases, with a focus on the small-molecule inhibitor GSK-J4. The H3K27 demethylase inhibitor ameliorated the early diabetic kidney disease lesions in diabetic mice . Mar 17, 2020 · Kruidenier L, Chung C, Cheng Z, Liddle J, Che K, Joberty G, et al. Feb 16, 2018 · The prototypic JMJD3/UTX (Jumonji domain-containing protein 3) H3K27 demethylase inhibitor GSK-J4 increased global levels of the repressive H3K27me3 mark around transcription start sites of effector cytokine genes. Dec 6, 2021 · 78. A Apr 30, 2018 · Treatment of tumor cells with the H3K27 demethylase inhibitor GSKJ4 immediately before irradiation prevented the radiation-induced decrease in H3K27me3 and enhanced radiosensitivity. Jul 26, 2017 · A novel synthetic histone 3 lysine 27 (H3K27) demethylase JMJD3 inhibitor, GSK-J4, was proven to exert immunosuppressive activities in macrophages. 1A). Potent and selective H3K27 histone demethylase inhibitor (IC50 = 60 nM, JMJD3). PubMed Abstract | CrossRef Full Text | Google Scholar Feb 23, 2024 · The utilization of PRC2 inhibitors has been extensively investigated in various cancer models, and several of these inhibitors are currently under clinical evaluation. Mar 17, 2020 · The antischistosomal potential of GSK-J4, an H3K27 demethylase inhibitor: insights from molecular modeling, transcriptomics and in vitro assays Jessica Lobo-Silva et al. We investigated the impact of increased H3K27me3 on CSCs using a selective H3K27 demethylase inhibitor GSKJ4. JCO 42 , e20035-e20035 (2024). Parasit Vectors . Unexpectedly, GSK-J4 has been shown to be able to induce DNA methylation of latent HIV-1, but unfortunately, the induction of DNA methylation by GSK-J4 on HIV-1 was only maintained in the presence of GSK-J4 and could May 10, 2023 · GSK-J4 is a histone demethylase inhibitor that inhibits the JMJD3/UTX enzyme, which results in the upregulation of H3K27me3 levels.