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は、強力かつ特異的なEZH2メチルトランスフェラーゼ阻害剤です。
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.
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. In C57Bl/6 mice bearing murine B16-F10 tumors, this chemical significantly reduces global H3K27me3 levels, inhibits tumor growth and virtually abolishes metastases formation.

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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