GSK343   Click here for help

GtoPdb Ligand ID: 8240

Synonyms: compound 6 [PMID 24900432] [2] | GSK 343
PDB Ligand Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: GSK343 is a cell-permeable inhibitor of EZH2 histone H3 methyltransferase activity, developed by GlaxoSmithKline and included in the Structural Genomics Consortium's (SGCs) portfilio of epigenetic probe compounds [1-2].
Click here to link to the SGC's full list of epigenetics probes.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 7
Hydrogen bond donors 2
Rotatable bonds 9
Topological polar surface area 99.15
Molecular weight 541.32
XLogP 6.35
No. Lipinski's rules broken 1
SMILES / InChI / InChIKey
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Canonical SMILES CCCc1cc(C)[nH]c(=O)c1CNC(=O)c1cc(cc2c1cnn2C(C)C)c1ccnc(c1)N1CCN(CC1)C
Isomeric SMILES CCCc1cc(C)[nH]c(=O)c1CNC(=O)c1cc(cc2c1cnn2C(C)C)c1ccnc(c1)N1CCN(CC1)C
InChI 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)
InChI Key ULNXAWLQFZMIHX-UHFFFAOYSA-N
Immunopharmacology Comments
GSK343 has been used to demonstrate that inhibition of EZH2 alleviates experimental intestinal inflammation [3]. In this study pharmacological inhibition of EZH2 increased the population of functional myeloid-derived suppressor cells (MDSCs) in the gut, which in turn produced immunosuppressive disease-modifying effects. These findings identify EZH2 inhibition as a potential therapeutic approach for the treatment of inflammatory bowel disease. The authors also caution that the use of EZH2 inhibitors in oncology may suppress beneficial anticancer immunity (by increasing MDSC populations).