GSK503

製品コードS7804 バッチS780402

印刷

化学情報

Chemical Structure Synonyms N/A Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C31H38N6O2
分子量 526.67 CAS No. 1346572-63-1
Solubility (25°C)* 体外 DMSO 100 mg/mL (189.87 mM)
Ethanol (warmed with 50ºC water bath) 4 mg/mL (7.59 mM)
Water Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
* <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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 GSK503 is a potent and specific EZH2 methyltransferase inhibitor.
in vitro GSK503 inhibits the methyltransferase activity of WT and mutant EZH2 with similar potency. In a panel of seven DLBCL cell lines, this compound 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, this compound inhibits tumor growth. [1] In C57Bl/6 mice bearing murine B16-F10 tumors, this chemical significantly reduces global H3K27me3 levels, inhibits tumor growth and virtually abolishes metastases formation. [2]

プロトコル(参考用のみ)

キナーゼアッセイ In vitro biochemical assays against histone acetylases
GSK503 is profiled to assess inhibition against a panel of histone acetylases. This compound 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.

参考

  • https://pubmed.ncbi.nlm.nih.gov/23680150/
  • https://pubmed.ncbi.nlm.nih.gov/25609585/

カスタマーフィードバック

Data from [Data independently produced by , , J Pathol, 2018, 245(4):433-444]

Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：

Inhibition of histone methyltransferase EZH2 for immune-interception of colorectal cancer in Lynch syndrome [ JCI Insight, 2025, e177545] PubMed: 39946195
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
Epigenetic drift of H3K27me3 in aging links glycolysis to healthy longevity in Drosophila [ Elife, 2018, 7e35368] PubMed: 29809154
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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