Home Epigenetics Histone Methyltransferase inhibitor - EZH1/2 inhibitor - Autophagy activator GSK343

GSK343

Catalog No.S7164

For research use only.

GSK343 is a potent and selective EZH2 inhibitor with IC50 of 4 nM in a cell-free assay, showing 60 fold selectivity against EZH1, and >1000 fold selectivity against other histone methyltransferases. GSK343 induces autophagy.

GSK343 Chemical Structure

CAS No. 1346704-33-3

Selleck's GSK343 has been cited by 45 publications

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Biological Activity

Description GSK343 is a potent and selective EZH2 inhibitor with IC50 of 4 nM in a cell-free assay, showing 60 fold selectivity against EZH1, and >1000 fold selectivity against other histone methyltransferases. GSK343 induces autophagy.
Features A chemical probe for the SGC epigenetics initiative. Potential use in a variety of solid tumors.
Targets
EZH2 [1]
(Cell-free assay)		 EZH1 [1]
(Cell-free assay)
4 nM 240 nM
In vitro

GSK343 inhibits trimethylation of H3K27 (H3K27me3) with IC50 of 174 nM in HCC1806 breast cancer cells. GSK343 potently inhibits cell proliferation in breast cancer cells and prostate cancer cells, and the prostate cancer cell line LNCaP is the most sensitive to GSK343, with IC50 of 2.9 μM. [1] GSK343 significantly suppresses the growth of EOC cells cultured in 3D matrigel extracellular matrix (ECM), which mimics the tumor microenvironment in vivo. In addition, GSK343 also induces apoptosis of EOC cells in 3D and significantly inhibits the invasion of EOC cells. [2]
Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
2D10  Mm\sSpVv[3Srb36gRZN{[Xl? NXzVPVBlOC5{NT2yMlAh|ryP MXm5OkBp NH;kNZpz\WS3Y3XzJJRwfGGuIHPlcIx2dGG{IITybY1mfGi7bHH0[YQhUDONMkegbY4h[SC2aX3lMUBidmRiZH;z[U1l\XCnbnTlcpQhdWGwbnXy MVG8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPjB2MUK4O{c,OjZyNEGyPFc9N2F-
MDA-MB-231 NYDYcWdZT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MViwMVIxKM7:TR?= Ml;kO|IhcA>? NUH5RWc1e2ixd4OgZ5l1d3SxeHnjbZR6KGmwIHGg[I9{\S2mZYDlcoRmdnRibXHucoVz NUfrcZNQRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkWyNFM3OjZpPkK1NlA{PjJ4PD;hQi=>
MDA-MB-231 MYTGeY5kfGmxbjDBd5NigQ>? MYCxNEDPxE1? NVizNVZxPzJiaB?= MXzy[YR2[2W|IITo[UBt\X[nbDDv[kBJO0t{Nz3t[VM> MWe8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTJyM{[yOkc,OjV{MEO2NlY9N2F-
MDA-MB-231 M1ixd2Z2dmO2aX;uJGF{e2G7 M4ixcFExKM7:TR?= NFjHU5A4OiCq NXTaVVF7cW6mdXPld{BNSzNvSVmgZYNkfW23bHH0bY9v MWm8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPTJyM{[yOkc,OjV{MEO2NlY9N2F-
MDA-MB-231 NE[4SItHfW6ldHnvckBCe3OjeR?= Ml7TNVAh|ryP M2XyeFI1KGh? MV7pcoR2[2W|IHH1eI9xcGGpeR?= MlfpQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjV{MEO2NlYoRjJ3MkCzOlI3RC:jPh?=
HepG2 NIL2dotIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MYmwMVIxKM7:TR?= MWq3NkBp MX\zbI94eyCleYTveI95cWOrdImgbY4h[SCmb4PlMYRmeGWwZHXueEBu[W6wZYK= NIHzTG89[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUKwN|YzPid-MkWyNFM3OjZ:L3G+
A549 NWLle2FpT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= Ml21NE0zOCEQvF2= M3fYc|czKGh? MmC1d4hwf3NiY4n0c5RwgGmlaYT5JIlvKGFiZH;z[U1l\XCnbnTlcpQhdWGwbnXy NInjflE9[SC2YYLn[ZQ:L1:kbHHub{chcHKnZk2nbJR1eHN8Lz;weYJu\WRwbnPibU5vdG1wbnnoModwfi9{NUKwN|YzPid-MkWyNFM3OjZ:L3G+
HepG2 MXHGeY5kfGmxbjDBd5NigQ>? NVn5Vmt1OTBizszN M{HEOFI1KGh? M{nreIlv\HWlZYOgZZV1d3CqYXf5 NXKzXJR1RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkWyNFM3OjZpPkK1NlA{PjJ4PD;hQi=>
A549 NU[zVng5TnWwY4Tpc44hSXO|YYm= MnfXNVAh|ryP Mn3NNlQhcA>? MXHpcoR2[2W|IHH1eI9xcGGpeR?= NWfZcG5zRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkWyNFM3OjZpPkK1NlA{PjJ4PD;hQi=>
OVCAR10 Mn\YS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? M{nrd|Eh|ryP MlS2NE0yOiCm NHr4c5RFVVOR MoO2bY5pcWKrdIOgZ4VtdCCpcn;3eIghfGmvZTDk[ZBmdmSnboTsfS=> NXzHWIZsRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO3OVk2QDlpPkKzO|U6PTh7PD;hQi=>
UPN289 NHnX[5JIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWLhdZdTOSEQvF2= MnO0NE0yOiCm Mm[1SG1UVw>? M2fyN4lvcGmkaYTzJINmdGxiZ4Lve5RpKHSrbXWg[IVx\W6mZX70cJk> NWDLW5lDRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkO3OVk2QDlpPkKzO|U6PTh7PD;hQi=>
SKOV3  M3fZO2dzd3e2aDDJcohq[mm2aX;uJGF{e2G7 M1[4R|Eh|ryP NWe2XndYOC1zMjDk NHTVN2JFVVOR NGriV5hqdmirYnn0d{Bk\WyuIHfyc5d1cCC2aX3lJIRmeGWwZHXueIx6 MUS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zOzd3OUW4PUc,OjN5NUm1PFk9N2F-
SKOV3  M1rZVmFxd3C2b4Ppd{BCe3OjeR?= NE\xRmUyKM7:TR?= NUPsPFg2PCCm MkjLSG1UVw>? NIrZcpZqdmS3Y3XzJIFxd3C2b4Ppd{BkfWy2dYLl[EBqdiB|RDDjc45lcXSrb37z MkH5QIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjN5NUm1PFkoRjJ|N{W5OVg6RC:jPh?=
HCC1806 NYPW[Yl6TnWwY4Tpc44h[XO|YYm= MVm3NkBpenN? NVLGN4ZkUW6qaXLpeIlwdiCxZjDFXmgzNW2nZHnheIVlKG63Y3zlZZIhUDONMkegcYV1cHmuYYTpc44hcW5iaIXtZY4hUEOFMUiwOkBk\WyuczDh[pRmeiB5MjDodpMh[nliaX3teY5w\my3b4Lld4NmdmOnIHHuZYx6e2m|LDDJR|UxKD1iMD6xO|Qh|ryPLh?= NVO5UZhDRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFA1OzJpPkK0PVAxPDN{PD;hQi=>
LNCaP Mln0SpVv[3Srb36gZZN{[Xl? M3;uOlYh\GG7cx?= MUTJcohq[mm2aX;uJI9nKEWcSEKtcYVlcWG2ZXSgdJJwdGmoZYLheIlwdiCxZjDoeY1idiCOTlPhVEBk\WyuczDh[pRmeiB4IHThfZMh[nliY3jlcYltfW2rbnXzZ4Vv[2ViYX7hcJl{cXNuIFnDOVAhRSB{Lkmg{txONg>? M1XZVFxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4D1Zo1m\C6wY3LpMo5tdS6waXiu[493NzJ2OUCwOFMzLz5{NEmwNFQ{OjxxYU6=
DU145 M{m5VWZ2dmO2aX;uJIF{e2G7 MVG2JIRigXN? MYjJcohq[mm2aX;uJI9nKEWcSEKtcYVlcWG2ZXSgdJJwdGmoZYLheIlwdiCxZjDoeY1idiCGVUG0OUBk\WyuczDh[pRmeiB4IHThfZMh[nliY3jlcYltfW2rbnXzZ4Vv[2ViYX7hcJl{cXN? MYS8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyMESzNkc,OjR7MEC0N|I9N2F-
SKBR3 NWXQPY1FTnWwY4Tpc44h[XO|YYm= NXy0RnBOPiCmYYnz M4DQdWlvcGmkaYTpc44hd2ZiRWrINk1u\WSrYYTl[EBxem:uaX\ldoF1cW:wIH;mJIh2dWGwIGPLRnI{KGOnbHzzJIFnfGW{IE[g[IF6eyCkeTDjbIVucWy3bXnu[ZNk\W6lZTDhcoFtgXOrcx?= MoPPQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xcIXicYVlNm6lYnmucoxuNm6raD7nc5YwOjR7MEC0N|IoRjJ2OUCwOFMzRC:jPh?=
PC3 NEH5VmtHfW6ldHnvckBie3OjeR?= NF\xU3c3KGSjeYO= NIPuT4VKdmirYnn0bY9vKG:oIFXaTFIudWWmaXH0[YQheHKxbHnm[ZJifGmxbjDv[kBpfW2jbjDQR|Mh[2WubIOgZYZ1\XJiNjDkZZl{KGK7IHPo[Y1qdHWvaX7ld4NmdmOnIHHuZYx6e2m| NYLuVHZ2RGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFA1OzJpPkK0PVAxPDN{PD;hQi=>
ZR-75-1 M13YNWZ2dmO2aX;uJIF{e2G7 NVX4T|dnPiCmYYnz Mk[wTY5pcWKrdHnvckBw\iCHWliyMY1m\GmjdHXkJJBzd2yrZnXyZZRqd25ib3[gbJVu[W5iWmKtO|UuOSClZXzsd{Bi\nSncjC2JIRigXNiYomgZ4hmdWmudX3pcoV{[2WwY3WgZY5idHm|aYO= NWjKUYNCRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:vdJVjdWWmLn7jZokvdmyvLn7pbE5od3ZxMkS5NFA1OzJpPkK0PVAxPDN{PD;hQi=>
HCC180 NXjXUFFiTnWwY4Tpc44h[XO|YYm= NWfWTopDPiCmYYnz MV\Jcohq[mm2aX;uJI9nKEWcSEKtcYVlcWG2ZXSgdJJwdGmoZYLheIlwdiCxZjDoeY1idiCKQ1OxPFAh[2WubIOgZYZ1\XJiNjDkZZl{KGK7IHPo[Y1qdHWvaX7ld4NmdmOnIHHuZYx6e2m| MV[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:ydXLt[YQvdmOkaT7ucI0vdmmqLnfvek8zPDlyMESzNkc,OjR7MEC0N|I9N2F-
Click to View More Cell Line Experimental Data
Assay
Methods Test Index PMID
Western blot H3K27me3 ; EZH2 / EED / SUZ12 ; N-cadherin / Vimentin / Snail / Slug / MMP2 / MMP9 29228694
Immunofluorescence N-cadherin / H3K27me3 / Vimentin 29228694
Growth inhibition assay Cell viability 26973856

Protocol (from reference)

Kinase Assay:[1]
  • In vitro biochemical assays against histone methyltransferases:

    Activity against EZH2 is assessed using 5 member PRC2 complex (Flag-EZH2, EED, SUZ12, AEBP2, RbAp48). The assay protocol may be summarized as follows: 10 mM stocks of compounds are prepared from solid in 100% DMSO. An 11 point serial dilution master plate is prepared in 384 well format (1:3 dilution, columns 6 and 18 were equal volume DMSO controls) and dispensed to assay ready plates using acoustic dispensing technology to create a 100 nL stamp of compound and DMSO controls. The assay additions consisted of equal volume additions of 10 nM EZH2 and the substrate solution (5 µg/mL HeLa nucleosomes and 0.25 µM [3H]-SAM) dispensed into assay plates using a multi-drop combi dispense. Reaction plates are incubated for 1 hr and quenched with an equal volume addition of 0.5 mg/mL PS-PEI Imaging Beads (RPNQ0098) containing 0.1 mM unlabeled SAM. The plates are sealed, dark adapted for 30 minutes, and a 5 minute endpoint luminescence image is acquired using a Viewlux imager. Plate statistics such as Z’ and signal to background as well as dose response curves are analyzed using Activity BaseXE. The in vitro biochemical activity of EZH1 is assessed as part of a 5 member PRC2 complex using a 384 well SPA assay identical to EZH2. Buffer components, reagent dispensing, compound plate preparation, quench conditions and data analysis are identical for EZH1 and EZH2 with final assay concentrations of 20 nM EZH1, 5 μM/mL HeLa nucleosomes and 0.25 μM [3H]-SAM. Further data analysis, pIC50 pivots and visualizations are enabled by TIBCO Spotfire. Compounds are profiled at Reaction Biology Corp. (Malvern, PA) to assess inhibition in their panel of histone methyltransferase assays. Methyltransferase activity is assessed using HotSpot technology, a miniaturized radioisotope-based filter binding assay. Inhibitors are dissolved in dimethyl sulfoxide (DMSO) and tested at concentrations up to 100 uM with a final DMSO concentration of 2%. Buffer containing the methyltrasferase at the listed concentration and its preferred substrate as shown in the accompanying table is preincubated with compound for 10 min. Reactions are initiated by the addition of 1 uM S-adenosyl-L-[methyl-3H]methionine (SAM), allowed to incubate for 60 min at 30C followed by transfer to P81 filter-paper and PBS wash before detection.
Cell Research:[1]
  • Cell lines: Breast cancer cell lines (HCC1806, Sk-Br-3, ZR-75-1), prostate cancer cell lines (DU145, PC3, LNCaP)
  • Concentrations: ~50 μM
  • Incubation Time: 6 days
  • Method: To account for varying doubling rates among cancer cell lines, the optimal cell seeding is determined empirically for all cell lines by examining their growth in a 384-well plate over 6 days with a wide range of seeding densities. Cells are then plated at the optimal seeding density and allowed to adhere overnight. Cells are treated in duplicate with a 20-point 2-fold dilution series of compound or 0.147% DMSO (vehicle control) and incubated for 6 days at 37C in 5% CO2. Cells are then lysed with 25 μl CellTiter-Glo per well and chemiluminescence is quantified 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 after 6 days of treatment were expressed as a percent of the T0 value and plotted against compound concentration. Data are fit with a 4-parameter equation to generate a concentration response curve and the concentration of compound required to inhibit 50% of growth (gIC50) is determined

Solubility (25°C)

In vitro

Chemical Information

Molecular Weight 541.69
Formula

C31H39N7O2
CAS No. 1346704-33-3
Storage 3 years -20°C powder
2 years -80°C in solvent
Smiles CCCC1=C(C(=O)NC(=C1)C)CNC(=O)C2=C3C=NN(C3=CC(=C2)C4=CC(=NC=C4)N5CCN(CC5)C)C(C)C

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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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