Name: GSK126
Price: 225.00 USD

- Overview
  - Please contact us at for specific academic pricing.
    
    Background
    
    GSK126 is an inhibitor of EZH2 with Ki Value of 93 pM [1].
    Over-expression of EZH2 has been reported to be correlated with cancer progression and poor prognosis, high grade and high stage in several tumor types. GSK126 is a potent inhibitor of EZH2 and its functional residence time on activated form of EZH2/PRC2 is mush longer than unactivated forms [1]. When tested with lymphoma cell lines, results showed that harboring EZH2 mutations such as Y641N, Y641F or A677G were more sensitivity [2]. In DMS53, Lu30, H209 SCLC cells, cellular growth was inhibited with 0.5, 2, and 8 μM GSK126 treatment [3]. And GSK126 could also significantly restore ARNTL expression in ovarian cancer cells thus inhibit cell growth and enhance chemosensitivity of cisplatin [4].
    Intermittent dosing of GSK126 treated subcutaneous KARPAS-422 xenografts model could effectively inhibit its growth with or without a 1 week drug holiday. In mouse model with EZH2 mutant DLBCL xenografts, treatment with GSK126 could markedly inhibit its growth [2].
    
    1. Sato, T., et al., PRC2 overexpression and PRC2-target gene repression relating to poorer prognosis in small cell lung cancer. Sci Rep, 2013. 3(1911).
    2. McCabe, M.T., et al., EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations. Nature, 2012. 492(7427): p. 108-12.
    3. Van Aller, G.S., et al., Long residence time inhibition of EZH2 in activated polycomb repressive complex 2. ACS Chem Biol, 2014. 9(3): p. 622-9.
    4. Yeh, C.M., et al., Epigenetic silencing of ARNTL, a circadian gene and potential tumor suppressor in ovarian cancer. Int J Oncol, 2014. 45(5): p. 2101-7.
- Properties
  - Alternative Name
    
    EZH2 inhibitor;GSK-126;GSK 126; 1-[(2S)-butan-2-yl]-N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-3-methyl-6-(6-piperazin-1-ylpyridin-3-yl)indole-4-carboxamide
    
    CAS Number
    
    1346574-57-9
    
    Molecular Formula
    
    C31H38N6O2
    
    Molecular Weight
    
    526.67
    
    Purity
    
    99.74%
    
    Solubility
    
    insoluble in H2O; insoluble in EtOH; ≥4.38 mg/mL in DMSO with gentle warming
    
    Storage
    
    Store at -20°C
    
    * For Research Use Only
- Reference
  - 1. Baokun Sui, Dong Chen, et al. "A novel antiviral lncRNA, EDAL, shields a T309 O-GlcNAcylation site to promote EZH2 lysosomal degradation." Genome Biol 2020 Sep 1;21(1):228. PMID:32873321
    2. Meng XL, Fu P, et al. "Increased EZH2 Levels in Anterior Cingulate Cortex Microglia Aggravate Neuropathic Pain by Inhibiting Autophagy Following Brachial Plexus Avulsion in Rats." Neurosci Bull. 2020;10.1007/s12264-020-00502-w. PMID:32346844
    3. Silasi M, You Y, et al. "Human Chorionic Gonadotropin modulates CXCL10 Expression through Histone Methylation in human decidua." Sci Rep. 2020;10(1):5785. PMID:32238853
    4. Otsuka Y, Nishikori M, et al. "EZH2 inhibitors restore epigenetically silenced CD58 expression in B-cell lymphomas." Mol Immunol. 2020;119:35–45. PMID:31962268
    5. Liu Y, Niu Y, et al. "Tat expression led to increased histone 3 tri-methylation at lysine 27 and contributed to HIV latency in astrocytes through regulation of MeCP2 and Ezh2 expression." J Neurovirol. 2019 Apr 24. PMID:31020497
    6. Hübner JM, Müller T, et al. "EZHIP / CXorf67 mimics K27M mutated oncohistones and functions as an intrinsic inhibitor of PRC2 function in aggressive posterior fossa ependymoma." Neuro Oncol. 2019 Mar 29. pii: noz058. PMID:30923826
    7. Anastassiia Vertii, Jianhong Ou, et al. "Two Contrasting Classes of Nucleolus-Associated Domains in Mouse Fibroblast Heterochromatin." bioRxiv. 2018 December 03.
    8. Agnieszka I. Laskowski, Danielle A. Fanslow1,et al. "Clinical Epigenetic Therapies Disrupt Sex Chromosome Dosage Compensation in Human Female Cells." Gender and the Genome 2018, Vol. 2(1) 2-7
    9. Jalan-Sakrikar N, De Assuncao TM, et al. "Hedgehog Signaling Overcomes an EZH2-Dependent Epigenetic Barrier to Promote Cholangiocyte Expansion." PLoS One. 2016 Dec 9;11(12):e0168266. PMID:27936185

GSK126

GSK126

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