GSK343 / GSK - LARVOL DELTA

Enhancer of Zeste homolog 2-mediated histone H3 lysine 27 trimethylation silences LIM domain-containing protein 1 and activates hippo signaling in Mycoplasma pathogenesis. (PubMed, Int J Biol Macromol) - "Pharmacological blockade of EZH2 with GSK343 significantly reduced MG burden, highlighting the pathogenic role of H3K27me3...Collectively, our findings uncover a novel EZH2-H3K27me3-LIMD1-Hippo-YAP1 axis that governs host susceptibility to MG infection. Targeting this epigenetic circuit may offer novel strategies for host-directed therapy against avian mycoplasmosis."

Journal • Infectious Disease • Inflammation • Respiratory Diseases • YAP1

Inhibition of Enhancer of Zeste Homolog 2 Alleviates Oxidative Stress, Inflammation and Barrier Damage of Human Corneal Epithelial Cells. (PubMed, Exp Eye Res) - "Furthermore, GSK343 decreased the number of apoptotic cells and p53 positive cells, highlighting its protective properties. These findings suggest that GSK343 exerts anti-inflammatory, antioxidant, and epithelial-protective effects in DED models, suggesting EZH2 inhibition as a potential therapeutic strategy for DED management."

Journal • Corneal Abrasion • Dry Eye Disease • Inflammation • Ophthalmology • IL17A • IL1B • IL6 • OCLN • SOD2 • TJP1 • TNFA

Assessing the selective impact of histone modifying drugs on adenoid cystic carcinoma cells and their stem cell counterparts. (PubMed, BMC Cancer) - "These findings demonstrate that CSCs and non‑CSCs respond differently to epigenetic modulation, suggesting that personalized combination therapies targeting both subpopulations may be necessary to improve treatment outcomes for ACC. Although these targeted therapies are still in the early stages of investigation, our study provides a promising pre-clinical foundation for the development of effective, personalized therapeutic strategies for this challenging malignancy."

Journal • Adenoid Cystic Carcinoma • Oncology • Salivary Gland Cancer • EGFR

EZH2 promotes endometriosis progression through estrogen receptor and TNFα expression. (PubMed, Front Endocrinol (Lausanne)) - "Thus, EZH2 promotes TNFα-driven inflammation, contributing to endometriosis. Targeting EZH2, as with GSK343, could be a promising therapeutic strategy for endometriosis treatment."

Journal • Endometriosis • Gynecology • Infertility • Inflammation • Musculoskeletal Pain • Oncology • Pain • Sexual Disorders • Women's Health • ER • TNFA

GSK343, an inhibitor of EZH2, prevents acquired cisplatin resistance in bladder cancer. (PubMed, Mol Genet Genomics) - "Furthermore, the apoptosis rate was significantly increased in resistant cells treated with 20 µM GSK343. The study demonstrates that GSK343 inhibits EZH2-mediated H3K27me3 and overcomes acquired CDDP resistance in BCa cells, suggesting its therapeutic potential for BCa patients with limited benefit from chemotherapy."

Journal • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor

Antitumor Potential of GSK343 in Breast Cancer Cells: An in vitro Study. (BBCS 2025) - "The GSK343 inhibitor can exert significant cytotoxic and antiproliferative effects, especially in MDA-MB-231 cells, suggesting greater sensitivity of the triple negative subtype to EZH2 inhibition. These findings indicate the therapeutic potential of GSK343 as an epigenetic agent in aggressive breast cancers and reinforce the need for further studies for clinical validation."

Preclinical • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • HER-2

GSK343 and EZH2: Epigenetic Modulation in Breast Tumor Cells. (BBCS 2025) - "GSK343 is effective in negatively modulating EZH2 expression in breast cancer cells of different subtypes, with effects dependent on dose and exposure time, reinforcing its potential as an epigenetic agent in antitumor therapeutic strategies."

Tumor cell • Breast Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • EZH2

Asxl1 loss in mice leads to microcephaly by regulating neural stem cell survival. (PubMed, Anim Cells Syst (Seoul)) - "Furthermore, Ezh2 target genes associated with apoptosis, such as Epha7 and Osr1, were upregulated in wild-type NSCs following GSK343 treatment but not significantly affected in Asxl1-deficient NSCs. These findings establish Asxl1 as a critical regulator of NSC survival and neurogenesis via Ezh2-mediated chromatin modification and provide insights into the mechanisms underlying microcephaly in developmental disorders."

Journal • Preclinical • CNS Disorders • Developmental Disorders • Psychiatry • ASXL1 • EPHA7

Histone methylation regulated by EZH2 promotes the formation of liver fibrosis and the inhibitory effect of Fuzheng Huayu Recipe (APASL 2025) - "Compared with the 6-week model group, EZH2 inhibitor GSK343 group and Fuzheng Huayu recipe group significantly decreased the levels of ALT and AST in serum liver function, the content of hydroxyproline in liver tissue, the Sirius red staining area and the gene and protein expression levels of EZH2 and H3K27me3 in liver tissue. Histone methylation regulated by EZH2 promotes the formation of liver fibrosis, and inhibition of histone methylation involved in EZH2 can significantly improve the degree of liver fibrosis in mice. The anti-liver fibrosis effect of Fuzheng Huayu recipe may be related to the inhibition of this link."

Epigenetic controller • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • EZH2

Screening and identification of gene expression in large cohorts of clinical tissue samples unveils the major involvement of EZH2 and SOX2 in lung cancer. (PubMed, Cancer Genet) - "Molecular docking analyses predicted most probable inhibitors of EZH2. We employed several predictive analysis tools and identified GSK343, as a promising inhibitor of EZH2."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • SOX2

Epigenetic Suppression of miR-137 Induces RNF4 Expression, Facilitating Wnt Signaling in Colorectal Cancer. (PubMed, Mol Carcinog) - "EZH2-mediated H3K27 trimethylation silences miR-137 in CRC cells by increasing chromatin compaction, reversible by EZH2 siRNA or inhibitor GSK343...It regulates the Wnt signaling pathway by targeting RNF4, leading to c-Myc and β-catenin destabilization. Restoring miR-137 or inhibiting RNF4 suppresses CRC cell proliferation, migration, invasion, and tumor growth, highlighting its therapeutic potential in CRC."

Journal • Colorectal Cancer • Oncology • Solid Tumor • CTNNB1 • EZH2 • MYC

Histone modification H3K27me3 is essential during chilling-induced flowering in Litchi chinensis. (PubMed, Plant Physiol) - "To probe the functional role of H3K27me3, we employed GSK343, a histone H3 lysine methyltransferase inhibitor...Overexpression of LcSVP10 in Arabidopsis thaliana delayed flowering, indicating a conserved function in flowering time control. Our results elucidate the molecular and epigenetic mechanisms that govern floral induction in litchi and highlight the potential of epigenetic modifications to regulate flowering time in horticultural plants."

Epigenetic controller • Journal • CTPS1

EZH2 inhibition sensitizes retinoic acid-driven senescence in synovial sarcoma. (PubMed, Cell Death Dis) - "Exposure to GSK343 or ATRA results in inhibition of cell proliferation and induction of cellular senescence, where GSK343 shows a dominant effect. The Figure was created with Biorender.com."

Journal • Melanoma • Oncology • Sarcoma • Solid Tumor • Synovial Sarcoma • PRAME • RARA • SS18

Combined inhibition of histone methyltransferases EZH2 and DOT1L is an effective therapy for neuroblastoma. (PubMed, Cancer Med) - "Our results support further investigation of HMT inhibitor combinations as a therapeutic approach in NB."

Epigenetic controller • Journal • CNS Tumor • Neuroblastoma • Oncology • Solid Tumor • ATF4 • DOT1L • EZH2

Super-silencer perturbation by EZH2 and REST inhibition leads to large loss of chromatin interactions and reduction in cancer growth. (PubMed, Nat Struct Mol Biol) - "To perturb the super-silencers, we applied combinational treatment of an enhancer of zeste homolog 2 inhibitor GSK343, and a repressor element 1-silencing transcription factor inhibitor, X5050 ('GR')...Moreover, GR synergistically upregulated super-silencer-controlled genes related to cell cycle, apoptosis and DNA damage, leading to anticancer effects in vivo. Overall, our data demonstrated a super-silencer example and showed that GR can disrupt super-silencers, potentially leading to cancer ablation."

Journal • Oncology • FGF18 • TOP2A

EZH2 Inhibition to Counteract Oral Cancer Progression through Wnt/β-Catenin Pathway Modulation. (PubMed, Pharmaceuticals (Basel)) - "Moreover, GSK343 reduced the expression of inflammatory mediators; eNOS and TGFβ, markers of angiogenesis; and CD31 and CD34, markers of micro vessel density, respectively. In conclusion, our data demonstrate that GSK343 counteracts oral cancer progression through EZH2/Wnt/β-catenin pathway modulation, suggesting that it could be a promising therapeutic approach for OSCC management."

Journal • Head and Neck Cancer • Oncology • Oral Cancer • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • CD31 • CD34 • NFKBIA • NOS3 • PECAM1 • TGFB1

Enhancer of zeste homolog 2 (EZH2) as a new therapeutic target to prevent indoxyl-sulfate-induced aortic valve calcification (ERA-EDTA 2024) - "This work demonstrates that IS-induced macrophages' secretion of IL-6 promotes hVICs osteogenic transition and mineralization. Our data suggest that IL-6 secretion in response to IS depends on the EZH2-p65 pathway. The fact that GSK-343 can block this mechanism sheds light on EZH2 as a new therapeutic target to prevent CAVD in CKD patients."

Chronic Kidney Disease • Inflammation • Nephrology • Renal Disease • CCL2 • EZH2 • GLI2 • IL1B • IL6 • RUNX2 • TNFA

Iron overload increases the sensitivity of endometriosis stromal cells to ferroptosis via a PRC2-independent function of EZH2. (PubMed, Int J Biochem Cell Biol) - "In addition, the activity or expression of EZH2 is directly and specifically inhibited by the methyltransferase inhibitor GSK343, which raises the sensitivity of stromal cells to ferroptosis. Taken together, our findings revealed that EZH2 act as a suppressor in the induced cell ferroptosis through a PRC2-independent methyltransferase mechanism. Therefore, blocking EZH2 expression and inducing ferroptosis may be effective treatment approaches for ovarian endometriosis."

Journal • Stroma • Endometriosis • Gynecology • Hematological Disorders • Women's Health • EZH2

EZH2 Inhibitor Improves Cognitive Behavior in CAA (ISC 2024) - "The present study investigates the therapeutic potential of an EZH2 inhibitor (GSK343) in CAA mice... Our study revealed that EZH2 expression is upregulated in the brain of CAA-model mice. Pharmacological inhibition of EZH2 improved cognitive outcomes in CAA mice, suggesting a possible therapeutic target."

Alzheimer's Disease • Cardiovascular • CNS Disorders • Dementia • Inflammation • EZH2

GSK343 modulates macrophage M2 polarization through the EZH2/MST1/YAP1 signaling axis to mitigate neurological damage induced by hypercalcemia in CKD mice. (PubMed, Cell Signal) - "Specifically, GSK343 downregulated the expression of histone methyltransferase EZH2 and upregulated MST1, which suppressed YAP1, promoting M2 macrophage polarization and thereby, alleviating neural injury in hypercalcemia arising from renal failure. This molecular pathway introduced herein not only sheds light on the cellular machinations behind CKD-induced neurological harm but also paves the way for potential therapeutic interventions targeting the identified axis, especially considering the M2 macrophage polarization as a potential strategy to mitigate hypercalcemia-induced neural injuries."

Journal • Preclinical • Chronic Kidney Disease • Endocrine Disorders • Metabolic Disorders • Nephrology • Renal Disease • EZH2 • YAP1

Targeting polycomb repressor complex 2-mediated bivalent promoter epigenetic silencing of secreted frizzled-related protein 1 inhibits cholangiocarcinoma progression. (PubMed, Clin Transl Med) - "Overall, our data strongly suggested that targeting PRC2 promotes the expression of SFRP1, thereby inhibiting the progression of CCA."

Journal • Biliary Cancer • Cholangiocarcinoma • Gastrointestinal Cancer • Oncology • Solid Tumor • DNMT3A • EZH2 • SFRP1 • SUZ12

Treatment of calcific arterial disease via enhancement of autophagy using GSK343. (PubMed, iScience) - "In vivo experiments involve pharmacological and genetic activation of autophagy using mouse models of spontaneous large (Mgp) and small (Abcc6) artery calcification. Taken together, these data advance our mechanistic understanding of vascular calcification and provide important insights for a broad range of cardiovascular diseases involving VSMC phenotype switch."

Journal • Atherosclerosis • Cardiovascular • Dyslipidemia • ABCC6

PRRX1 Is a Master Regulator of Renal Fibroblast Cell Fate and Regulates Myofibroblast Activation in Response to TGF-β via Alteration of the Chromatin Landscape (KIDNEY WEEK 2023) - "Single cell RNA-sequencing (scRNA-seq) was performed on iPSC derived kidney organoids treated with EZH2 inhibitor, GSK343, for 1h prior to TGFβ1 treatment for 48 hours. Mass Spectrometry data revealed differential abundance of trimethylated lysine residues on Histone 3 (H3K27me3) between TGFβ treated and control, indicating dynamic changes in transcriptionally permissive states... TGF-β is a key driver of chromatin dynamics as evidenced by H3K27me3 and likely contributes to gene repression through interaction between SMAD3 and EZH2. We propose that subsequent silencing of PRRX1 expression mediates fibroblast to myofibroblast activation and represent a tractable therapeutic target for the amelioration of fibrosis in DKD."

Diabetic Nephropathy • Fibrosis • Immunology • Nephrology • Renal Disease • PRRX1 • SMAD3 • TGFB1

Ezh2 emerges as an epigenetic checkpoint regulator during monocyte differentiation limiting cardiac dysfunction post-MI. (PubMed, Nat Commun) - "In line with this protective effect, GSK-343 treatment accelerated cardiac inflammatory resolution preventing infarct expansion and subsequent cardiac dysfunction in female mice post-MI in vivo. In conclusion, our study reveals that pharmacological epigenetic modulation of cardiac-infiltrating immune cells may hold promise to limit adverse cardiac remodeling after MI."

Journal • Cardiovascular • Immune Modulation • Myocardial Infarction

Neuroprotective effects of GSK-343 in an in vivo model of MPTP-induced nigrostriatal degeneration. (PubMed, J Neuroinflammation) - "Furthermore, GSK-343 administration significantly attenuated the neuroinflammatory state through the modulation of canonical and non-canonical NF-κB/IκBα pathway as well as the cytokines expression and glia activation, also reducing the apoptosis process. In conclusion, the obtained results provide further evidence that epigenetic mechanisms play a pathogenic role in PD demonstrating that the inhibition of EZH2, mediated by GSK-343, could be considered a valuable pharmacological strategy for PD."

Journal • Preclinical • CNS Disorders • Inflammation • Movement Disorders • Parkinson's Disease • NFKBIA