GSK343 is a highly potent and selective EZH2 inhibitor with an IC50 of 4 nM.
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GSK343 Estructura química
No. CAS : 1346704-33-3
This product is a controlled substance and not for sale in your territory.
Based on 29 publication(s) in Google Scholar
GSK343 purchased from MedChemExpress. Usage Cited in:
Nat Chem Biol. 2023 Mar 27.
[Abstract]
GSK343 (1, 2.5, 5, 10 μM; 72 h) reduces the level of H3K27me3 in wild-type and CXCdel+/− Karpas-422 cells.
GSK343 purchased from MedChemExpress. Usage Cited in:
Int Immunopharmacol. 2023 Apr 10;119:110155.
[Abstract]
GSK343 (2.5 mg/kg; i.p.; 32 weeks) reduces extensive IgG deposition in the kidneys of lupus mice.(once every other day for the first 16 weeks, then twice a week for 8 weeks, and finally once a week for 8 weeks)
GSK343 purchased from MedChemExpress. Usage Cited in:
Theranostics. 2019 Jan 24;9(3):761-777.
[Abstract]
Immunoblot analysis of the indicated proteins in lysates from cells as in G with α-Tubulin as loading control with or without the treatment of GSK343.
GSK343 purchased from MedChemExpress. Usage Cited in:
Oncol Lett. 2018 Jul;16(1):1231-1236.
[Abstract]
EZH2 protein expression in T24 cells treated with methyl jasmonate alone or in combination with GSK343 is analyzed using western blot analysis.
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GSK343 is a highly potent and selective EZH2 inhibitor with an IC50 of 4 nM.
IC50 & Target
EZH2
Cellular Effect
Cell Line
Type
Value
Description
References
HCC1806
IC50
174 nM
Compound: 6, GSK343
Inhibition of EZH2-mediated nuclear H3K27 methylation in human HCC1806 cells after 72 hrs by immunofluorescence analysis
Inhibition of EZH2-mediated nuclear H3K27 methylation in human HCC1806 cells after 72 hrs by immunofluorescence analysis
[PMID: 24900432]
LNCaP
IC50
2.9 μM
Compound: 6, GSK343
Inhibition of EZH2-mediated proliferation of human LNCaP cells after 6 days by chemiluminescence analysis
Inhibition of EZH2-mediated proliferation of human LNCaP cells after 6 days by chemiluminescence analysis
[PMID: 24900432]
In Vitro
GSK343, which contains an n-propyl group at the 4-position of the pyridone, has EZH2 Kiapp=1.2±0.2 nM. In this 6-day proliferation assay, among the cell lines evaluated in this study, the prostate cancer cell line LNCaP is the most sensitive to EZH2 inhibition, with growth IC50 value of 2.9 μM for GSK343[1]. GSK343 is found to have half maximal inhibitory concentration values of 13 μM in HeLa cells and 15 μM in SiHa cells[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
GSK343 Related Antibodies
In Vivo
Compare with the controls, GSK343 (5 mg/kg)-treated mice exhibits significantly inhibited tumor growth. The average tumor volume and weight of the GSK343-treated cohort is remarkably reduced. As early as 20 days post-implantation, a significant reduction in tumor growth is observed in the GSK343-treated cohort relative to the control cohort; this difference persisted through the remainder of the study. In addition, compare with the control cohort, the GSK343-treated animals in the xenograft model show a remarkable increase in messenger RNA levels of E-cadherin but a significant decrease in vimentin messenger RNA levels[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Room temperature in continental US; may vary elsewhere.
Almacenamiento
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
2 years
-20°C
1 year
Solvente y solubilidad
In Vitro:
DMSO : 15.62 mg/mL (28.84 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
H2O : < 0.1 mg/mL (insoluble)
Preparing Stock Solutions
ConcentrationSolventMass
1 mg
5 mg
10 mg
1 mM
1.8461 mL
9.2304 mL
18.4607 mL
5 mM
0.3692 mL
1.8461 mL
3.6921 mL
10 mM
0.1846 mL
0.9230 mL
1.8461 mL
View the Complete Stock Solution Preparation Table
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day. The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
This protocol yields a clear solution of ≥ 1.56 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (15.6 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 2
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
This protocol yields a clear solution of ≥ 1.56 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (15.6 mg/mL) to 900 μLCorn oil, and mix evenly.
For the following dissolution methods, please prepare the working solution directly.
It is recommended to prepare fresh solutions and use them promptly within a short period of time. The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution.
If precipitation or phase separation occurs during preparation,
heat and/or sonication can be used to aid dissolution.
Protocol 1
Add each solvent one by one: 0.5% CMC-Na/saline water
Solubility: 2 mg/mL (3.69 mM); Suspended solution; Need ultrasonic
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
Dosage
mg/kg
Animal weight (per animal)
g
Dosing volume (per animal)
μL
Number of animals
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO+
%
+
%
Tween-80
+
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO,
. All of co-solvents are available by MedChemExpress (MCE).
, Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration:
mg/mL
Method for preparing stock solution:
mg
drug dissolved in
μL
DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take
μL DMSO stock solution, add
μL .
μL , mix evenly, next add
μL Tween 80, mix evenly, then add
μL Saline.
Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution
If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
[1]. Sharad K, et al. Identification of Potent, Selective, Cell-Active Inhibitors of the Histone Lysine Methyltransferase EZH2. ACS Med Chem Lett. 2012 Oct 19;3(12):1091-6.
[Content Brief]
[2]. Ding M, et al. The polycomb group protein enhancer of zeste 2 is a novel therapeutic target for cervical cancer. Clin Exp Pharmacol Physiol. 2015 May;42(5):458-64.
[Content Brief]
Ensayo de quinasas
[1]
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 GSK343 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 are equal volume DMSO controls) and dispensed to assay ready plates using acoustic dispensing technology to create a 100 nL stamp of GSK343 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 ActivityBaseXE. 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, GSK343 plate preparation, quench conditions and data analysis are identical for EZH1 and EZH2 with final assay concentrations of 20 nM EZH1, 5 μg/mL HeLa nucleosomes and 0.25 μM [3H]-SAM. Further data analysis, pIC50 pivots and visualizations are enabled by TIBCO Spotfire[1].
MCE no ha confirmado la precisión de estos métodos independientemente. Son solo para referencia.
Ensayo celular
[1]
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 GSK343 or 0.147% DMSO (vehicle control) and incubated for 6 days at 37°C 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 GSK343 addition (T0) to quantify the starting number of cells. CTG values after 6 days of treatment are expressed as a percent of the T0 value and plotted against GSK343 concentration. Data are fit with a 4-parameter equation to generate a concentration response curve and the concentration of GSK343 required to inhibit 50% of growth (gIC50) is determined[1].
MCE no ha confirmado la precisión de estos métodos independientemente. Son solo para referencia.
Administraciòn de animales
[2]
Mice[2] Six-week-old female nude BALB/c mice are used. To study the effect of the EZH2 inhibitor GSK343, 5 mg/kg in 100-μL phosphate-buffered saline is injected intraperitoneally every other day into BALB/c nude mice (n=6) after the tumor volume reaches 100 mm3. In this analysis, the negative control group (n=6) received saline. After 40 days, the mice are killed, and the subcutaneous tumors are surgically excised, weighed, photographed, sectioned, and fixed in 10% formalin. The expression levels of E-cadherin, N-cadherin, and vimentin in the tumours are measured by real-time reverse transcription polymerase chain reaction.
MCE no ha confirmado la precisión de estos métodos independientemente. Son solo para referencia.
Referencias
[1]. Sharad K, et al. Identification of Potent, Selective, Cell-Active Inhibitors of the Histone Lysine Methyltransferase EZH2. ACS Med Chem Lett. 2012 Oct 19;3(12):1091-6.
[Content Brief]
[2]. Ding M, et al. The polycomb group protein enhancer of zeste 2 is a novel therapeutic target for cervical cancer. Clin Exp Pharmacol Physiol. 2015 May;42(5):458-64.
[Content Brief]
[1]. Sharad K, et al. Identification of Potent, Selective, Cell-Active Inhibitors of the Histone Lysine Methyltransferase EZH2. ACS Med Chem Lett. 2012 Oct 19;3(12):1091-6.
[2]. Ding M, et al. The polycomb group protein enhancer of zeste 2 is a novel therapeutic target for cervical cancer. Clin Exp Pharmacol Physiol. 2015 May;42(5):458-64.
Complete Stock Solution Preparation Table
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Optional Solvent
ConcentrationSolventMass
1 mg
5 mg
10 mg
25 mg
DMSO
1 mM
1.8461 mL
9.2304 mL
18.4607 mL
46.1519 mL
5 mM
0.3692 mL
1.8461 mL
3.6921 mL
9.2304 mL
10 mM
0.1846 mL
0.9230 mL
1.8461 mL
4.6152 mL
15 mM
0.1231 mL
0.6154 mL
1.2307 mL
3.0768 mL
20 mM
0.0923 mL
0.4615 mL
0.9230 mL
2.3076 mL
25 mM
0.0738 mL
0.3692 mL
0.7384 mL
1.8461 mL
GSK343 Related Classifications
EpigeneticsAutophagy
Histone MethyltransferaseAutophagy
Help & FAQs
Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.
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