EED226 - 10mM in DMSO, high purity , CAS No.2083627-02-3

  • 10mM in DMSO
Item Number
E422525
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E422525-1ml
1ml
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$218.90

Epigenetic Reader Domain Inhibitors

Basic Description

Specifications & Purity10mM in DMSO
Biochemical and Physiological MechanismsEED226 is a potent, selective, and orally bioavailable a novel allosteric Polycomb repressive complex 2 (PRC2) inhibitor with an IC50 of 23.4 nM when the H3K27me0 peptide was used as substrate and an IC50 of 53.5 nM when the mononucleosome was used as the
Storage TempStore at -80°C
Shipped InIce chest + Ice pads
Product Description

Information

EED226 EED226 is a potent, selective, and orally bioavailable a novel allosteric Polycomb repressive complex 2 (PRC2) inhibitor with an IC50 of 23.4 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.

Targets

EED ; PRC2 82 nM(Kd); 114 nM(Kd)

In vitro

EED226 induces a conformational change upon binding EED, leading to loss of PRC2 activity. EED226 also effectively inhibits PRC2 containing a mutant EZH2 protein resistant to SAM-competitive inhibitors. It regulates histone H3K27 methylation and PRC2 target gene expression in cells. In the in vitro enzymatic assays, EED226 inhibits PRC2 with an IC50 (half-maximal inhibitory concentration) of 23.4 nM when the H3K27me0 peptide is used as substrate and 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). EED226 is noncompetitive with both SAM and peptide substrate. EED226 bound to EED and PRC2 complex with a 1:1 stoichiometry and Kd of 82 nM and 114 nM, respectively. EED226 does not disrupt the PRC2 complex and could still occupy its binding pocket with a SAM-competitive EZH2 inhibitor bound to PRC2. EED226 shows remarkable selectivity for PRC2 complex over 21 other protein methyltransferases, kinases and other protein classes, The only other histone methyltransferase that can be inhibited by EED226 is the EZH1-PRC2 complex. EED226 with moderate permeability leads to a dose-dependent decrease of both global H3K27me3 and H3K27me2 markers in G401 cell.

In vivo

EED226 effectively induces tumor regression in a mouse xenograft model. EED226 in a solid dispersion formulation are well tolerated in animals. EED226 clearly demonstrates a dose-dependent efficacy in the mouse xenograph study. EED226 inhibits the growth of diffuse large B-cell lymphoma (DLBCL) xenografts and reduces H3K27me3 levels to a similar extent as an EZH2 inhibitor. EED226 has very low in vivo and in vitro clearance and approximately 100% oral bioavailability, low volume of distribution (0.8 L/kg), reasonable terminal t1/2 (2.2 h), and moderate plasma protein binding (PPB)(14.4%). Its solubility is relatively low and with little dependency on the pH of the medium.

Cell Research(from reference)

Cell lines:G401 cells 

Concentrations:0.12, 0.37, 1.1, 3.3, 10 μM 

Incubation Time:3 d 

Product Properties

ALogP2.136
HBD Count1
Rotatable Bond5

Associated Targets(Human)

EED Tchem Polycomb protein EED (7 Activities)
Activity TypeActivity Value -log(M)Mechanism of ActionActivity ReferencePublications (PubMed IDs)
ADRA2A Tclin Alpha-2a adrenergic receptor (9450 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
KCNH2 Tclin HERG (29587 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
ADRA2C Tclin Alpha-2c adrenergic receptor (4876 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CYP2D6 Tclin Cytochrome P450 2D6 (33882 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
AOX1 Tchem Aldehyde oxidase (429 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CYP2C9 Tchem Cytochrome P450 2C9 (32119 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
CYP3A4 Tclin Cytochrome P450 3A4 (53859 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Liver (3974 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
EED Tchem Polycomb protein EED (645 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
KARPAS-422 (454 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
EZH2 Tclin EZH2/SUZ12/EED complex (20 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Associated Targets(non-human)

Pde4d Phosphodiesterase 4D (4 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Hdac6 Histone deacetylase 6 (222 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Canis familiaris (36305 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Mus musculus (284745 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Rattus norvegicus (775804 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
rep Replicase polyprotein 1ab (378 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
Plasma (328 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID
SARS-CoV-2 (38078 Activities)
Activity TypeRelationActivity valueUnitsAction TypeJournalPubMed IddoiAssay Aladdin ID

Names and Identifiers

IUPAC Name N-(furan-2-ylmethyl)-8-(4-methylsulfonylphenyl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine
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)
InChi Key DYIRSNMPIZZNBK-UHFFFAOYSA-N
Canonical SMILES CS(=O)(=O)C1=CC=C(C=C1)C2=CN=C(N3C2=NN=C3)NCC4=CC=CO4
Isomeric SMILES CS(=O)(=O)C1=CC=C(C=C1)C2=CN=C(N3C2=NN=C3)NCC4=CC=CO4
PubChem CID 123132228
Molecular Weight 369.4

Certificates

Certificate of Analysis(COA)

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Chemical and Physical Properties

DMSO(mg / mL) Max Solubility73
DMSO(mM) Max Solubility197.6177585
Water(mg / mL) Max Solubility<1

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