受注:045-509-1970 |
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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C31H38N6O2 |
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分子量 | 526.67 | CAS No. | 1346572-63-1 | |
Solubility (25°C)* | 体外 | DMSO | 100 mg/mL (189.87 mM) | |
Ethanol | 26 mg/mL warmed with 50ºC water bath (49.36 mM) | |||
Water | Insoluble | |||
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. |
製品説明 | GSK503 is a potent and specific EZH2 methyltransferase inhibitor. |
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in vitro | GSK503 inhibits the methyltransferase activity of WT and mutant EZH2 with similar potency. In a panel of seven DLBCL cell lines, GSK503 causes growth inhibition and the effects are enhanced by ABT737 or Obatoclax. [1] |
in vivo | In C57BL6 mice immunized with SRBC, GSK503 (150 mg/kg, i.p.) reduced the level of H3K27me3 in splenocytes. In male SCID mice bearing SUDHL4 and SUDHL6 tumors, GSK503 (150 mg/kg, i.p.) inhibits tumor growth. [1] In C57Bl/6 mice bearing murine B16-F10 tumors, GSK503 (150 mg/kg, i.p.) significantly reduces global H3K27me3 levels, inhibits tumor growth and virtually abolishes metastases formation. [2] |
キナーゼアッセイ | In vitro biochemical assays against histone acetylases | |
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GSK503 is profiled to assess inhibition against a panel of histone acetylases. GSK503 is dissolved in DMSO and tested in 10-dose IC50 mode with 3-fold serial dilution starting at 100 μM, with a final DMSO concentration of 2%. Anacardic Acid is used as positive control for CBP, GCN5, and pCAF and tested in 10-dose IC50 mode with 3-fold serial dilution starting at 100 μM. Curcumin is used as positive control for KAT5, MYST2/KAT7, MYST4/KAT6B, and p300, and tested in 10-dose IC50 mode with 3-fold serial dilution starting at 100 μM. Reactions are carried out at 3.08 μM Acetyl-CoA. For CBP, GCN5, MYST2/KAT7, pCAF, and p300, the substrate used is histone H3. For KAT5 and MYST4/KAT6B the substrates used are histone H2A and histone H4, respectively. | ||
細胞アッセイ | 細胞株 | OCI-Ly1, OCI-Ly7, OCI-Ly18, Pfeiffer, OCI-Ly19, OCI-Ly3, Farage, WSU-DLCL2, HBL-1, U2932, TMD8, SUDHL6, SUDHL5 and SUDHL4 cells |
濃度 | ||
反応時間 | 6 days | |
実験の流れ | DLBCL cell lines are grown at concentrations sufficient to keep untreated cells in exponential growth over the complete drug exposure time. Cell viability is determined using a fluorometric resazurin reduction method and trypan blue automatic method. Fluorescence (Ex560nm / Em590nm) is determined with the Synergy4 microplate reader. The number of viable cells is calculated by using the linear least-squares regression of the standard curve. The fluorescence is determined for three replicates per treatment condition and normalized to their respective controls. To plot dose-effect curves CompuSyn software is used, and drug concentrations that inhibit the growth of the cell lines by 50% compared to control (GI50) are determined. Data were presented as the mean GI50 with a 95% confidence interval for duplicate experiments. | |
動物実験 | 動物モデル | Male SCID mice bearing SUDHL4 and SUDHL6 tumors |
投薬量 | 150 mg/kg daily | |
投与方法 | i.p. |
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Data from [Data independently produced by , , J Pathol, 2018, 245(4):433-444]
Study on the Effect of EZH2 Inhibitor Combined with TIGIT Monoclonal Antibody against Multiple Myeloma Cells [ Int J Mol Sci, 2023, 24(10)8603] | PubMed: 37239949 |
PRC2-mediated epigenetic suppression of type I IFN-STAT2 signaling impairs antitumor immunity in luminal breast cancer [ Cancer Res, 2022, CAN-22-0736] | PubMed: 36222718 |
EZH2-mediated H3K27me3 is a predictive biomarker and therapeutic target in uveal melanoma [ Front Genet, 2022, 13:1013475] | PubMed: 36276954 |
An Evolutionarily Conserved Function of Polycomb Silences the MHC Class I Antigen Presentation Pathway and Enables Immune Evasion in Cancer. [ Cancer Cell, 2019, 36(4):385-401] | PubMed: 31564637 |
Epigenetic Reprogramming with Antisense Oligonucleotides Enhances the Effectiveness of Androgen Receptor Inhibition in Castration-Resistant Prostate Cancer [ Cancer Res, 2018, 78(20):5731-5740] | PubMed: 30135193 |
Overexpression of EZH2 in conjunctival melanoma offers a new therapeutic target [Cao J, et al. J Pathol, 2018, 245(4):433-444] | PubMed: 29732557 |
Human Papillomavirus Downregulates the Expression of IFITM1 and RIPK3 to Escape from IFNγ- and TNFα-Mediated Antiproliferative Effects and Necroptosis. [Ma W, et al. Front Immunol, 2016, 7:496] | PubMed: 27920775 |
長期の保管のために-20°Cの下で製品を保ってください。
人間や獣医の診断であるか治療的な使用のためにでない。
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