GSK126

SKU: orb1306533

Description

GSK126 (GSK2816126A) is a potent and selective EZH2 methyltransferase inhibitor (IC50=9.9 nM). It demonstrates antitumor activity in research by inhibiting the proliferation of cancer cells and suppressing angiogenesis, as shown in both in vitro and in vivo studies.

Research Area

Epigenetics & Chromatin

Key Properties

• CAS Number: 1346574-57-9
• MW: 526.67
• Purity: 99.67% (May vary between batches)
• Formula: C₃₁H₃₈N₆O₂
• SMILES: CC[C@H](C)n1cc(C)c2c(cc(cc12)-c1ccc(nc1)N1CCNCC1)C(=O)NCc1c(C)cc(C)[nH]c1=O
• Target: Histone Methyltransferase
• Solubility: DMSO:10.63 mg/mL (20.18 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:0.53 mg/mL (1.01 mM)

Bioactivity

• Target IC50:
  U266 cells:17.15 μM|EZH2:9.9 nM|OCL-MY5 cells:15.10 μM|RPMI8226 cells:17.43 μM|SGC-7901 cells:35.05 ± 1.13 µM|OPM2 cells:16.82 μM|AGS cells:38.48 ± 1.43 µM|LP1 cells:14.45 μM
• In Vivo:
  In both EZH2 wild-type and mutant DLBCL cell lines, GSK126 effectively inhibits H3K27me3 and H3K27me2, consequently suppressing cell proliferation. In parental H2087 cells, GSK126 curtails cell proliferation, migration, and metastasis by downregulating the expression of VEGF-A and phosphorylated Ser(473)-AKT. In A687V EZH2 mutant cells, GSK126 reduces H3K27me3 levels, leading to the inhibition of cell proliferation.
• In Vitro:
  In mice bearing human B-cell lymphoma cells and human diffuse large B-cell xenografts, treatment with GSK126 (150 mg/kg/d, i.p.) led to a reduction in H3K27me3, thereby inhibiting tumor cell proliferation.
• Cell Research:
  The optimal cell seeding is determined empirically for all cell lines by examining the growth of a wide range of seeding densities in a 384-well format to identify conditions that permitted proliferation for 6 days. Cells are then plated at the optimal seeding density 24 h before treatment (in duplicate) with a 20-point two fold dilution series of GSK126 or 0.15% DMSO. Plates are incubated for 6 days at 37°C in 5% CO2. Cells are then lysed with CellTiter-Glo (CTG) and chemiluminescent signal is detected with a TECAN Safire2 microplate reader. In addition, an untreated plate of cells is harvested at the time of compound addition (T0) to quantify the starting number of cells. CTG values obtained after the 6 day treatment are expressed as a percent of the T0 value and plotted against compound concentration. Data are fit with a four-parameter equation to generate a concentration response curve and the concentration of GSK126 required to inhibit 50% of growth (growth IC50) is determined.(Only for Reference)

Storage & Handling

• Storage: store at low temperature,keep away from direct sunlight | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Inhibitor, HistoneMethyltransferase, Histone Methyltransferase, GSK 126, GSK126, GSK-126, GSK2816126A, EZH2, EZH2 inhibitor, inhibit

Compound Identifiers

PubChem CID

68210102