product name EED226
Description: EED226 is a novel, potent, selective, and orally bioavailable, allosteric embryonic ectoderm development (EED) inhibitor with an IC50 of 22 nM when the H3K27me0 peptide was used as substrate and an IC50 of 53.5 nM when the mononucleosome was used as the substrate. It directly binds to the H3K27me3 binding pocket of EED. EED226 induces a conformational change upon binding EED, leading to loss of PRC2 activity.
References: Nat Chem Biol. 2017 Apr;13(4):381-388; Cancer Discov. 2017 Apr;7(4):OF8.
369.40
Formula
C17H15N5O3S
CAS No.
2083627-02-3
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 73 mg/mL (197.6 mM)
Water: <1 mg/mL
Ethanol: <1 mg/mL
Solubility (In vivo)
Synonyms
other peoduct :References PubMed ID：:http://www.ncbi.nlm.nih.gov/pubmed/19419966
| In Vitro |
In vitro activity: EED226 is a highly potent, efficient and selective inhibitor of EZH2 and EZH1 evaluated against a broad range of epigenetic and non-epigenetic targets. It potently reduces global H3K27Me3 mark in cells and demonstrates selectively cell killing effects in cells carrying a heterozygous Y641N mutation. EED226 has moderate permeability as the measured in Caco-2 cells at A→B=3.0×10-6 cm/s, with an efflux ratio at 7.6. Kinase Assay: Cell Assay: G401 cells are treated with EED226 for 3 d at the indicated concentrations. Total histone H3 is shown as a loading control. WB analysis for protein expression of H3K27me3, H3K27me2, H3K27me1. |
|---|---|
| In Vivo | EED226 induces robust and sustained tumor regression in EZH2MUT pre-clinical DLBCL model. In CD-1 mice, dosing of EED226 for 14 days at 300 mg/kg bid is well tolerated with no apparent adverse effects. It has very low in vivo clearance, and approximately 100% oral bioavailability. EED226 has low volume of distribution (0.8 L/kg), reasonable terminal t1/2 (2.2 h), and moderate plasma protein binding (PPB). |
| Animal model | Karpas422 xenograft tumors (mouse model) |
| Formulation & Dosage | Dissolved in 75% Soluplus + 5% sodium laureth sulfate + 20% EED226; 10 ml/kg ; Oral gavage |
| References | Nat Chem Biol. 2017 Apr;13(4):381-388; Cancer Discov. 2017 Apr;7(4):OF8. |
