GSK343
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MedKoo CAT#: 406270

CAS#: 1346704-33-3

Description: GSK343 is a potent, selective inhibitor of EZH2 with cellular activity. GSK343 inhibits EZH2 with an IC50 of 4nM and is over 1000-fold selective for other HMTs except EZH1 (60-fold selectivity). GSK343 inhibits H3K27 methylation in HCC1806 cells with an IC50 of <200nM as measured by immunofluorescence. GSK343 exhibited limited effects on the growth of EOC cells in conventional two-dimensional (2D) culture. In contrast, GSK343 significantly suppressed the growth of EOC cells cultured in 3D matrigel extracellular matrix (ECM), which more closely mimics the tumor microenvironment in vivo. Notably, GSK343 induces apoptosis of EOC cells in 3D but not 2D culture. In addition, GSK343 significantly inhibited the invasion of EOC cells.

Chemical Structure

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GSK343
CAS# 1346704-33-3
Product data Instruction

Theoretical Analysis

MedKoo Cat#: 406270
Name: GSK343
CAS#: 1346704-33-3
Chemical Formula: C31H39N7O2
Exact Mass: 541.32
Molecular Weight: 541.690
Elemental Analysis: C, 68.74; H, 7.26; N, 18.10; O, 5.91

Price and Availability

Size Price Availability Quantity
25mg USD 150 Ready to ship
50mg USD 250 Ready to ship
100mg USD 450 Ready to ship
200mg USD 750 Ready to ship
500mg USD 1550 Ready to ship
1g USD 2850 Ready to ship
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Synonym: GSK343; GSK-343; GSK 343.

IUPAC/Chemical Name: 1-isopropyl-N-((6-methyl-2-oxo-4-propyl-1,2-dihydropyridin-3-yl)methyl)-6-(2-(4-methylpiperazin-1-yl)pyridin-4-yl)-1H-indazole-4-carboxamide.

InChi Key: ULNXAWLQFZMIHX-UHFFFAOYSA-N

InChi Code: InChI=1S/C31H39N7O2/c1-6-7-23-14-21(4)35-31(40)26(23)18-33-30(39)25-15-24(16-28-27(25)19-34-38(28)20(2)3)22-8-9-32-29(17-22)37-12-10-36(5)11-13-37/h8-9,14-17,19-20H,6-7,10-13,18H2,1-5H3,(H,33,39)(H,35,40)

SMILES Code: O=C(C1=CC(C2=CC(N3CCN(C)CC3)=NC=C2)=CC4=C1C=NN4C(C)C)NCC5=C(CCC)C=C(C)NC5=O

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

More Info:         

Biological target: GSK343 is an EZH2 inhibitor with an IC50 of 4 nM.
In vitro activity: As shown in Figure 2A, GSK343 increased the level of mature SREBP2, but not SREBP1, in both HepG2 and PLC5 cells. Although the expression of SREBP1 precursor in PLC5 cells was reduced by GSK343, no increase of mature SREBP1 was observed. To confirm the activation of SREBP2, the nuclear localization and DNA binding activity of SREBP1/2 were examined. Consistently, GSK343 increased nuclear level and DNA binding ability of SREBP2, but not SREBP1, in HepG2 and PLC5 cells (Figure 2B and 2C). Reference: Am J Cancer Res. 2019; 9(10): 2120–2139. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6834481/
In vivo activity: GSK343, which is an EZH2 inhibitor, was used to treat CLP mice to observe whether inhibition of EZH2 could protect the intestine against sepsis-induced injury. At the end of the experiment, animals were sacrificed and H&E staining was performed on small intestinal tissue sections. Fig. 2A demonstrates the results of H&E staining in the intestinal tissues of mice in different groups. The ileum tissue structure of the mice in the sham operation group was normal, the intestinal villi were arranged neatly and the villi structure was clear. In the CLP group, however, evident edema, hyperemia, necrosis and inflammatory cell infiltration were observed, accompanied by missing apical epithelial cells of the villi and thinner and shorter microvilli. Compared with the CLP group, the intestinal structure of the mice in the GSK343 treatment group was relatively normal, with relieved intestinal villi edema and inflammation. The levels of inflammatory cytokines, including TNF-α, IL-1β and IL-6, in the serum and intestinal tissues of mice in different groups are presented in Fig. 2B and C. It was indicated that CLP stimulation significantly promoted the production of all inflammatory cytokines, and this increase was reversed by GSK343 treatment. Reference: Exp Ther Med. 2021 May; 21(5): 437. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7967880/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 31.9 58.82
Ethanol 7.0 12.92
DMF 25.0 46.15
DMF:PBS (pH 7.2) (1:1) 0.5 0.92

Preparing Stock Solutions

The following data is based on the product molecular weight 541.69 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Yang PM, Hong YH, Hsu KC, Liu TP. p38α/S1P/SREBP2 activation by the SAM-competitive EZH2 inhibitor GSK343 limits its anticancer activity but creates a druggable vulnerability in hepatocellular carcinoma. Am J Cancer Res. 2019 Oct 1;9(10):2120-2139. PMID: 31720078; PMCID: PMC6834481. 2. Xiong X, Zhang J, Li A, Dai L, Qin S, Wang P, Liu W, Zhang Z, Li X, Liu Z. GSK343 induces programmed cell death through the inhibition of EZH2 and FBP1 in osteosarcoma cells. Cancer Biol Ther. 2020;21(3):213-222. doi: 10.1080/15384047.2019.1680061. Epub 2019 Oct 25. PMID: 31651209; PMCID: PMC7012145. 3. Yue D, Wang Z, Yang Y, Hu Z, Luo G, Wang F. EZH2 inhibitor GSK343 inhibits sepsis-induced intestinal disorders. Exp Ther Med. 2021 May;21(5):437. doi: 10.3892/etm.2021.9854. Epub 2021 Feb 26. PMID: 33747174; PMCID: PMC7967880. 4. Bownes LV, Williams AP, Marayati R, Stafman LL, Markert H, Quinn CH, Wadhwani N, Aye JM, Stewart JE, Yoon KJ, Mroczek-Musulman E, Beierle EA. EZH2 inhibition decreases neuroblastoma proliferation and in vivo tumor growth. PLoS One. 2021 Mar 9;16(3):e0246244. doi: 10.1371/journal.pone.0246244. PMID: 33690617; PMCID: PMC7942994.
In vitro protocol: 1. Yang PM, Hong YH, Hsu KC, Liu TP. p38α/S1P/SREBP2 activation by the SAM-competitive EZH2 inhibitor GSK343 limits its anticancer activity but creates a druggable vulnerability in hepatocellular carcinoma. Am J Cancer Res. 2019 Oct 1;9(10):2120-2139. PMID: 31720078; PMCID: PMC6834481. 2. Xiong X, Zhang J, Li A, Dai L, Qin S, Wang P, Liu W, Zhang Z, Li X, Liu Z. GSK343 induces programmed cell death through the inhibition of EZH2 and FBP1 in osteosarcoma cells. Cancer Biol Ther. 2020;21(3):213-222. doi: 10.1080/15384047.2019.1680061. Epub 2019 Oct 25. PMID: 31651209; PMCID: PMC7012145.
In vivo protocol: 1. Yue D, Wang Z, Yang Y, Hu Z, Luo G, Wang F. EZH2 inhibitor GSK343 inhibits sepsis-induced intestinal disorders. Exp Ther Med. 2021 May;21(5):437. doi: 10.3892/etm.2021.9854. Epub 2021 Feb 26. PMID: 33747174; PMCID: PMC7967880. 2. Bownes LV, Williams AP, Marayati R, Stafman LL, Markert H, Quinn CH, Wadhwani N, Aye JM, Stewart JE, Yoon KJ, Mroczek-Musulman E, Beierle EA. EZH2 inhibition decreases neuroblastoma proliferation and in vivo tumor growth. PLoS One. 2021 Mar 9;16(3):e0246244. doi: 10.1371/journal.pone.0246244. PMID: 33690617; PMCID: PMC7942994.

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1: Amatangelo MD, Garipov A, Li H, Conejo-Garcia JR, Speicher DW, Zhang R. Three-dimensional culture sensitizes epithelial ovarian cancer cells to EZH2 methyltransferase inhibition. Cell Cycle. 2013 Jun 10;12(13). [Epub ahead of print] PubMed PMID: 23759589.