For research use only. Not for therapeutic Use.
EED226 is a polycomb repressive complex 2 (PRC2) inhibitor, which binds to the K27me3-pocket on embryonic ectoderm development (EED) and shows strong antitumor activity in xenograft mice model[1]. EED226 is a potent, selective, and orally bioavailable EED inhibitor[2]. EED226 inhibits PRC2 with an IC50 of 23.4 nM when the H3K27me0 peptide is used as a substrate in the in vitro enzymatic assays[3].
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[2].In the in vitro enzymatic assays, EED226 inhibited PRC2 with an IC50 of 53.5 nM when the mononucleosome is used as the substrate, with the stimulatory H3K27me3 added at 1× Kact (1.0 μM)[3].
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)[2].
| Catalog Number | I013724 |
| CAS Number | 2083627-02-3 |
| Synonyms | N-(furan-2-ylmethyl)-8-(4-methylsulfonylphenyl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine |
| Molecular Formula | C17H15N5O3S |
| Purity | ≥95% |
| InChI | InChI=1S/C17H15N5O3S/c1-26(23,24)14-6-4-12(5-7-14)15-10-19-17(22-11-20-21-16(15)22)18-9-13-3-2-8-25-13/h2-8,10-11H,9H2,1H3,(H,18,19) |
| InChIKey | DYIRSNMPIZZNBK-UHFFFAOYSA-N |
| SMILES | CS(=O)(=O)C1=CC=C(C=C1)C2=CN=C(N3C2=NN=C3)NCC4=CC=CO4 |
| Reference | [1]. Li L, et al. Discovery and Molecular Basis of a Diverse Set of Polycomb Repressive Complex 2 Inhibitors Recognition by EED. PLoS One. 2017 Jan 10;12(1):e0169855. [2]. Huang Y, et al. Discovery of First-in-Class, Potent, and Orally Bioavailable Embryonic Ectoderm Development (EED) Inhibitor with Robust Anticancer Efficacy. J Med Chem. 2017 Mar 23;60(6):2215-2226. [3]. Qi W, et al. An allosteric PRC2 inhibitor targeting the H3K27me3 binding pocket of EED. Nat Chem Biol. 2017 Apr;13(4):381-388. |
