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embryonic ectoderm development

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Target not currently curated in GtoImmuPdb

Target id: 2487

Nomenclature: embryonic ectoderm development

Family: Neutral sphingomyelinase coupling factors

Gene and Protein Information Click here for help
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 441 11q14.2 EED embryonic ectoderm development
Mouse - 441 7 Eed embryonic ectoderm development
Rat - 441 1q32 Eed embryonic ectoderm development
Previous and Unofficial Names Click here for help
Polycomb protein EED | WAIT-1 | WD protein associating with integrin cytoplasmic tails 1
Database Links Click here for help
Alphafold
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia

Download all structure-activity data for this target as a CSV file go icon to follow link

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
AZ14117230 Small molecule or natural product Hs Binding 9.3 pKd 4
pKd 9.3 (Kd 5.4x10-10 M) [4]
Description: Binding affinity determined by SPR assay
A-395 Small molecule or natural product Hs Binding 9.4 pKi 3
pKi 9.4 (Ki 4x10-10 M) [3]
Allosteric Modulators
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
FTX-6058 Small molecule or natural product Hs Negative >8.6 pKd 2
pKd >8.6 (Kd <2.5x10-9 M) [2]
Description: Binding affinity by SPR
MAK683 Small molecule or natural product Ligand has a PDB structure Hs Negative 8.2 pIC50 1
pIC50 8.2 (IC50 5.8x10-9 M) [1]
Description: Measuring test compound-mediated inhibition of EED-H3K27Me3 binding in a peptide competition binding assay using AlphaScreen technology.
Immuno Process Associations
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:1990830 cellular response to leukemia inhibitory factor IEA
General Comments
The EED protein is an essential subunit of the polycomb repressive complex 2 (PRC2). PRC2 trimethylates histone H3 at lysine 27 (H3K27me3) causing gene silencing. H3K27me3 marks are recognised, and the trimethyllysine bound by EED. The small molecule probe A-395 prevents EED binding to H3K27me3 histone marks and this blocks activation of the catalytic activity of PRC2.

References

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1. Chan HM, Gu X-JJ, Huang Y, Li L, Mi Y, Qi W, Sendzik M, Sun Y, Wang L, Yu Z et al.. (2016) Triazolopyrimidine compounds and uses thereof. Patent number: WO2016103155A1. Assignee: Novartis Ag. Priority date: 23/12/2014. Publication date: 20/06/2016.

2. Efremov IV, Kazmirski S, Li q, Thompson LA III, Wallace OW, Johnstone SD, Zhou F, Rahl P. (2020) MACROCYCLIC AZOLOPYRIDINE DERIVATIVES AS EED AND PRC2 MODULATORS. Patent number: WO2020190754. Assignee: FULCRUM THERAPEUTICS, INC. Priority date: 15/03/2019. Publication date: 24/09/2020.

3. He Y, Selvaraju S, Curtin ML, Jakob CG, Zhu H, Comess KM, Shaw B, The J, Lima-Fernandes E, Szewczyk MM et al.. (2017) The EED protein-protein interaction inhibitor A-395 inactivates the PRC2 complex. Nat Chem Biol, 13 (4): 389-395. [PMID:28135237]

4. Hsu JH, Rasmusson T, Robinson J, Pachl F, Read J, Kawatkar S, O' Donovan DH, Bagal S, Code E, Rawlins P et al.. (2020) EED-Targeted PROTACs Degrade EED, EZH2, and SUZ12 in the PRC2 Complex. Cell Chem Biol, 27 (1): 41-46.e17. [PMID:31786184]

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