GSK2816126

As EZH2 is highly expressed in numerous precancers, PPT@GSK126 has broad application prospects for reducing these tumor burdens. Schematic images presenting the mechanism of action regarding EZH2 in promoting MT of OLK into HNSCC via inhibiting MHC-I associated APM (left panel) and the proposed therapeutic strategy for preventing OLK carcinogenesis (right panel).

EZH2 inhibitors (EPZ6438, GSK126) were intraperitoneally injected. EZH2 inhibitors exerted potent anti-fibrotic effects in secondary lymphedema though activating PPARγ signaling, offering novel insights and strategies for fibrotic disorders. This study demonstrated that targeted inhibition of the EZH2-PPARγ axis effectively inhibited fibrogenic differentiation of AdMSCs and reduced fibroadipose tissue in secondary lymphedema, indicating it is a promising strategy for secondary lymphedema treatment, offering novel insights and strategy for musculoskeletal fibrotic disorders.

Notably, treatment with GSK126, a specific EZH2 inhibitor, reversed the chemoresistance induced by USP44 overexpression. USP44/EZH2 signaling pathway is one of the key to causing the drug resistance of TNBC, warranting further clinical investigation.

Additionally, GSK126 NPs can partially counteract the effects of GSK126 on MDSCs, particularly by decreasing the infiltration of M-MDSCs into tumors. Albumin-based EZH2i NPs have potent anti-cancer efficacy with tolerable adverse effects, providing promising opportunity for future clinical translation in treating solid tumors.

In conclusion, the observed synergistic antitumor effect could be partly due to increased intracellular accumulation, although this alone is certainly not sufficient to explain it. Overall, the developed method provides a valuable approach for characterizing interactions at the transport level and for predicting the efficiency of both anticancer substance classes in different cell lines.

NHD13 mice were treated with GSK126 (EZH2 inhibitor) and CXCL10 neutralizing antibody, with transformation time, blood cell counts and CD8+ T cell determined...EZH2-mediated H3K27me3 curbed CXCL10 transcription and secretion. Collectively, EZH2/H3K27me3 downregulates CXCL10 to facilitate CD8+ T-cell exhaustion, accelerating transformation from MDS to AML.

Our findings revealed that GSK126 induced apoptosis and autophagy, evidenced by increased markers like cleaved caspase-3 and LC3-II, and decreased cellular migration, through downregulation of the Fuse Binding Protein 1 (FBP1)/C-Myc axis. These findings suggest GSK126 as a promising therapeutic against osteosarcoma, offering a dual action of promoting cell death and hindering migration.

Furthermore, KDM2B knockdown increased the level of the transcriptionally repressive histone mark H3K27me3 on the key lytic gene pp38 promoter, accompanied by suppression of pp38 expression and reduced latent-to-lytic switch in MDV-latently infected cells, while treatment of cells with H3K27me3 inhibitors (GSK126 and Tazemetostat) markedly promoted the expression of pp38 and MDV reactivation from latency. Mechanistically, miR-M6-5p epigenetically suppressed the expression of the viral lytic gene pp38 by directly targeting the histone demethylase KDM2B. These findings will advance our understanding of the role of virus-encoded miRNA in the regulation of viral latency and will help guide the development of novel strategies for the effective control of MDV.

Our further experiments evidences indicated that ETV5 facilitated cell proliferation and reduced sensitivity to GSK126 via regulating EZH2. Collectively, this study comprehensively elucidates the carcinogenic effects and molecular mechanisms of ETV5 in tumorigenesis and development, and provides theoretical basis and guidance for tumor diagnosis, targeted therapy for ETV5 and clinical epigenetic drug research.

While GSK-J4 had minimal effects alone on TGCT tumor growth in vivo, it dramatically sensitized cisplatin-sensitive and -resistant TGCTs to cisplatin...Further, several chromatin modifier genes, including BRD4, lysine demethylases, chromodomain helicase DNA binding proteins, and lysine methyltransferases, were repressed with cisplatin only in KDM6A/KDM6B-targeted cells, implying that KDM6A/KDM6B inhibition sets the stage for extensive chromatin remodeling of TGCT cells upon cisplatin treatment. Our findings demonstrate that targeting polycomb demethylases is a new potent pharmacologic strategy for treating cisplatin resistant TGCTs that warrants clinical development.

He, we show that combined use of the EZH2 inhibitor GSK126 and the CDK4/6 inhibitor abemaciclib synergistically enhances antitumoral effects in preclinical GBM models. Mechanistically, this was due to transcriptional changes in genes involved in mitotic aberrations/spindle assembly (Rb, PLK1, RRM2, PRC1, CENPF, TPX2), histone modification (HIST1H1B, HIST1H3G), DNA damage/replication stress events (TOP2A, ATF4), immuno-oncology (DEPDC1), EMT-counterregulation (PCDH1) and a shift in the stemness profile towards a more differentiated state. We propose a dual EZH2/CDK4/6 blockade for further investigation.

Treatment with the EZH2 inhibitor GSK126 significantly reduced in vitro proliferation and increased cell-cycle arrest and apoptosis, which were partially mediated through the WNT pathway...This suggests that IL-11Rα promotes OS lung metastasis via activation of EZH2. Thus, blocking EZH2 activity may be an effective strategy for inhibiting OS lung metastasis and improving prognosis.