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Chemical Structure| 1346704-33-3 Chemical Structure| 1346704-33-3

Structure of GSK343
CAS No.: 1346704-33-3

Chemical Structure| 1346704-33-3

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GSK343 emerges as an exceptionally potent and selective inhibitor of EZH2, boasting an IC50 of 4 nM.

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Product Details of GSK343

CAS No. :1346704-33-3
Formula : C31H39N7O2
M.W : 541.69
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
MDL No. :MFCD25563250
InChI Key :ULNXAWLQFZMIHX-UHFFFAOYSA-N
Pubchem ID :71268957

Safety of GSK343

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Related Pathways of GSK343

epigenetics

Isoform Comparison

Biological Activity

Target
  • Histone Methyltransferase

    EZH1, IC50:240 nM

    EZH2, IC50:4 nM

In Vitro:

Cell Line
Concentration Treated Time Description References
mouse oocytes 1 µM 14 hours GSK343 treatment did not affect oocyte meiotic maturation but reduced the level of H3K27me3. PMC5027481
YB5 cells 1 µM 96 hours To study the effect of GSK343 on gene expression, it was found to affect only 1.2% of the transcriptome and preferentially targets genes marked with H3K27me3. PMC5243171
MCF7 cells 1 µM 96 hours To study the effect of GSK343 on gene expression, it was found to affect only 1.2% of the transcriptome and preferentially targets genes marked with H3K27me3. PMC5243171
HL60 cells 1 µM 96 hours To study the effect of GSK343 on gene expression, it was found to affect only 1.2% of the transcriptome and preferentially targets genes marked with H3K27me3. PMC5243171
SK-HEP-1 cells 3 μM 72 hours GSK343 treatment significantly increased CXCL10 expression and promoted NK cell migration. PMC8325240
PLC/PRF/5 cells 3 μM 72 hours GSK343 treatment significantly increased CXCL10 expression and promoted NK cell migration. PMC8325240
MDA-MB-231 2 µM 2 days Inhibited TNBC cell proliferation, induced G1 phase cell cycle arrest and cellular senescence PMC6376470
MDA-MB-436 2 µM 2 days Inhibited TNBC cell proliferation, induced G1 phase cell cycle arrest and cellular senescence PMC6376470
MCF7 2 µM 2 days Had minimal effect on non-TNBC cell proliferation PMC6376470
Human primary myoblasts 20 nM, 200 nM, 2 μM 10 days To assess the impact of the EZH2 inhibitor GSK343 on myoblast differentiation and fusion, measured by PAX7 and MYHC iμMunocytochemistry, and mitochondrial bioenergetics determined using the Seahorse XF96. Results showed that GSK343 treatment led to an increase in PAX7 expression (P≤0.05), decreased myotube fusion (P= 0.043), and an increase in ATP production (P= 0.008), with alterations in the DNA methylation of genes involved in oxidative phosphorylation and myogenesis. PMC8818655
B16 cells 10 mg/kg GSK343 impairs the phagocytosis of EMCDRs by macrophages, thereby inhibiting the tumor-promoting polarization of macrophages. PMC8899568
SYO-1 cells 2.5 µM 72 hours To evaluate the effect of GSK343 on the PRAME-EZH2 dimer, results showed that the combination treatment (GSK343 and ATRA) significantly disrupted the PRAME-EZH2 dimer in SYO-1 cells. PMC11569238
MoJo cells 2.5 µM 72 hours To evaluate the effect of GSK343 on the PRAME-EZH2 dimer, results showed that the combination treatment (GSK343 and ATRA) significantly disrupted the PRAME-EZH2 dimer in MoJo cells. PMC11569238

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
mice C57BL/6 mice intraperitoneal injection 10 mg/kg single injection GSK343 treatment significantly inhibited tumor growth, and this effect was dependent on NK cell activity. PMC8325240
Nude mice TNBC xenograft model Intraperitoneal injection 80 ng single dose, lasted for 20 hours Combination of GSK343 with chemotherapy drug Adriamycin significantly inhibited TNBC tumor growth, inducing cellular senescence and apoptosis PMC6376470
mice PGRN KO mice intraperitoneal 20 mg/kg 5 days per week for 28 days After treatment of PGRN KO mice with GSK343, the numbers of iNKT, NKT2, and IL-4+ cells were rescued to the same level as that of WT mice, and PLZF expression and airway hyperresponsiveness were also ameliorated. PMC9525702
mice B16 melanoma model subcutaneously 5 mg/kg Twice a week for 21 days GSK343 combined with PD1 monoclonal antibody significantly prolonged the survival of B16 melanoma-bearing mice and reduced the number of nodules in the lung and brain. PMC8899568
CD1 mice MPTP-induced Parkinson's disease model Intraperitoneal injection consecutively for 14 days GSK343 treatment significantly improved behavioral deficits and reduced the alteration of PD hallmarks. Furthermore, GSK343 administration significantly attenuated the neuroinflammatory state through the modulation of canonical and non-canonical NF-κB/IκBα pathway as well as the cytokines expression and glia activation, also reducing the apoptosis process. PMC10311910

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

1.85mL

0.37mL

0.18mL

9.23mL

1.85mL

0.92mL

18.46mL

3.69mL

1.85mL

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