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GSK126 (Synonyms: EZH2 inhibitor;GSK-126;GSK 126)

Katalog-Nr.GC15783

Ein selektiver EZH2-Inhibitor

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GSK126 Chemische Struktur

Cas No.: 1346574-57-9

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10mM (in 1mL DMSO)
69,00 $
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5mg
66,00 $
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10mg
95,00 $
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50mg
207,00 $
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100mg
289,00 $
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Sample solution is provided at 25 µL, 10mM.

Product Documents

Quality Control & SDS

View current batch:

Protocol

Kinase experiment [1]:

Inhibitory activities

Biochemical assays used the five-member PRC2 complex (human Flag-EZH2, EED, SUZ12, AEBP2, RbAp48) containing either wild-type or mutant EZH2, [3H]-SAM and histone H3 peptides (21-44) with K27me0, K27me1 or K27me2 were used as substrates, reactions were incubated for 30 min. Global histone modification levels were determined by enzyme-linked immunosorbent assay (ELISA) or western blot methods using antibodies specific for total histoneH3, H3K27me1, H3K27me2 orH3K27me3.

Cell experiment [2]:

Cell lines

Lu130, H209, and DMS53 small cell lung cancer (SCLC) cell lines.

Preparation method

Dissolved in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reaction Conditions

0.5, 2, and 8 μM; 72, 144, 192 h.

Applications

GSK126 inhibited cell growth in all the three cell lines at 8 μM.

Animal experiment [1]:

Animal models

Mice using subcutaneous xenografts of KARPAS-422 and Pfeiffer cells.

Dosage form

15, 50, 150 mg/kg, 10 days of once daily; 300 mg/kg twice per week; administered intraperitoneally.

Applications

GSK126 decreases H3K27me3 and increases gene expression in a dose-dependent way. GSK126 completely inhibited tumour growth at 50 mg/kg and increases survival of mice bearing the more aggressive KARPAS-422 tumours. GSK126 was well tolerated at the doses and schedules examined as measured by little to no decrease in body weight.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. McCabe MT, Ott HM, Ganji G, et al. EZH2 inhibition as a therapeutic strategy for lymphoma with EZH2-activating mutations. Nature, 2012, 492(7427): 108-112.

[2]. Sato T, Kaneda A, Tsuji S, et al. PRC2 overexpression and PRC2-target gene repression relating to poorer prognosis in small cell lung cancer. Sci Rep, 2013, 3: 1911.

Background

GSK126 ist ein Inhibitor von EZH2 mit einem Ki-Wert von 93 pM [1].

Eine Überexpression von EZH2 wurde bei mehreren Tumorarten mit Krebsprogression, schlechter Prognose, hohem Grad und Stadium in Verbindung gebracht. GSK126 ist ein potenter Inhibitor von EZH2 und seine funktionelle Verweildauer auf der aktivierten Form von EZH2/PRC2 ist länger als bei unaktivierten Formen [1]. Bei Tests mit Lymphomzelllinien zeigte sich, dass solche mit EZH2-Mutationen wie Y641N, Y641F oder A677G empfindlicher waren [2]. In DMS53-, Lu30- und H209-SCLC-Zellen wurde das Zellwachstum durch eine Behandlung mit 0,5, 2 bzw. 8 μM GSK126 gehemmt [3]. Und GSK126 konnte auch die ARNTL-Expression in Eierstockkrebszellen signifikant wiederherstellen und so das Zellwachstum hemmen sowie die Chemosensitivität von Cisplatin erhöhen [4].

Die intermittierende Dosierung von GSK126 konnte das Wachstum von subkutanen KARPAS-422 Xenografts effektiv hemmen, mit oder ohne eine einwöchige Medikamentenpause. In einem Mausmodell mit EZH2-mutierten DLBCL-Xenografts konnte die Behandlung mit GSK126 das Wachstum signifikant hemmen [2].

References:
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.

Chemical Properties

Cas No. 1346574-57-9 SDF
Überlieferungen EZH2 inhibitor;GSK-126;GSK 126
Chemical Name 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
Canonical SMILES CCC(C)N1C=C(C2=C(C=C(C=C21)C3=CN=C(C=C3)N4CCNCC4)C(=O)NCC5=C(C=C(NC5=O)C)C)C
Formula C31H38N6O2 M.Wt 526.67
Löslichkeit ≥ 3.29 mg/mL in DMSO, <2.4 mg/mL in EtOH, <2.27 mg/mL in Water Storage Store at -20°C
General tips Please select the appropriate solvent to prepare the stock solution according to the solubility of the product in different solvents; once the solution is prepared, please store it in separate packages to avoid product failure caused by repeated freezing and thawing.Storage method and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored at -20°C, please use it within 1 month.
To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time.
Shipping Condition Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request.

Complete Stock Solution Preparation Table

Prepare stock solution
1 mg 5 mg 10 mg
1 mM 1.8987 mL 9.4936 mL 18.9872 mL
5 mM 0.3797 mL 1.8987 mL 3.7974 mL
10 mM 0.1899 mL 0.9494 mL 1.8987 mL
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