EED

Summary

EED (embryonic ectoderm development, HGNC:3188) is a protein-coding gene on chromosome 11q14.2, encoding Polycomb protein EED (O75530). Polycomb group (PcG) protein. It is a selective cancer dependency (DepMap: 23.5% of cell lines).

This gene encodes a member of the Polycomb-group (PcG) family. PcG family members form multimeric protein complexes, which are involved in maintaining the transcriptional repressive state of genes over successive cell generations. This protein interacts with enhancer of zeste 2, the cytoplasmic tail of integrin beta7, immunodeficiency virus type 1 (HIV-1) MA protein, and histone deacetylase proteins. This protein mediates repression of gene activity through histone deacetylation, and may act as a specific regulator of integrin function. Two transcript variants encoding distinct isoforms have been identified for this gene.

Source: NCBI Gene 8726 — RefSeq curated summary.

At a glance

• Gene–disease (curated): Cohen-Gibson syndrome (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 3
• Clinical variants (ClinVar): 177 total — 5 pathogenic, 8 likely-pathogenic
• Phenotypes (HPO): 47
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 23.5% of screened cell lines
• MANE Select transcript: NM_003797

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:3188
Approved symbol	EED
Name	embryonic ectoderm development
Location	11q14.2
Locus type	gene with protein product
Status	Approved
Aliases	WAIT-1, HEED
Ensembl gene	ENSG00000074266
Ensembl biotype	protein_coding
OMIM	605984
Entrez	8726

Gene structure

Transcript identifiers

Ensembl transcripts: 14 — 9 protein_coding, 5 retained_intron

ENST00000263360, ENST00000327320, ENST00000351625, ENST00000524673, ENST00000525244, ENST00000527888, ENST00000528180, ENST00000528250, ENST00000533228, ENST00000534564, ENST00000534595, ENST00000672825, ENST00000673233, ENST00000707108

RefSeq mRNA: 3 — MANE Select: NM_003797 NM_001308007, NM_001330334, NM_003797

CCDS: CCDS76463, CCDS81612, CCDS8273

Canonical transcript exons

ENST00000263360 — 12 exons

Exon	Start	End
ENSE00001514890	86278399	86278810
ENSE00002194984	86244753	86245343
ENSE00003494253	86276980	86277138
ENSE00003516186	86257515	86257596
ENSE00003560025	86255222	86255287
ENSE00003587936	86252148	86252240
ENSE00003608084	86277918	86277991
ENSE00003609161	86256387	86256512
ENSE00003615608	86250296	86250448
ENSE00003623983	86266083	86266216
ENSE00003652990	86268456	86268561
ENSE00003657568	86264172	86264263

Expression profiles

Bgee: expression breadth ubiquitous, 159 present calls, max score 93.61.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 19.7645 / max 305.8048, expressed in 1804 samples.

FANTOM5 promoters (7 alternative TSS)

Promoter ID	TPM avg	Samples expressed
116097	13.0756	1789
116099	4.8282	1519
116100	0.8637	498
206408	0.4517	265
116098	0.2147	75
116101	0.1971	92
116102	0.1336	50

Top tissues by expression

159 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
endometrium epithelium	UBERON:0004811	93.61	gold quality
lymph node	UBERON:0000029	92.27	gold quality
endometrium	UBERON:0001295	90.72	gold quality
cerebellar vermis	UBERON:0004720	89.74	gold quality
cerebellar hemisphere	UBERON:0002245	89.62	gold quality
cortical plate	UBERON:0005343	89.61	gold quality
endocervix	UBERON:0000458	89.54	gold quality
cerebellar cortex	UBERON:0002129	89.54	gold quality
right uterine tube	UBERON:0001302	89.46	gold quality
epithelium of bronchus	UBERON:0002031	89.45	gold quality
mucosa of transverse colon	UBERON:0004991	89.40	gold quality
right hemisphere of cerebellum	UBERON:0014890	89.38	gold quality
cerebellum	UBERON:0002037	89.37	gold quality
uterus	UBERON:0000995	89.18	gold quality
left ovary	UBERON:0002119	88.96	gold quality
ventricular zone	UBERON:0003053	88.69	gold quality
vermiform appendix	UBERON:0001154	88.65	gold quality
spleen	UBERON:0002106	88.60	gold quality
body of uterus	UBERON:0009853	88.55	gold quality
vagina	UBERON:0000996	88.49	gold quality
embryo	UBERON:0000922	88.44	gold quality
ganglionic eminence	UBERON:0004023	88.44	gold quality
ovary	UBERON:0000992	88.43	gold quality
right ovary	UBERON:0002118	88.35	gold quality
myometrium	UBERON:0001296	88.25	gold quality
tonsil	UBERON:0002372	88.21	gold quality
skin of leg	UBERON:0001511	88.15	gold quality
skin of abdomen	UBERON:0001416	88.12	gold quality
zone of skin	UBERON:0000014	88.11	gold quality
ectocervix	UBERON:0012249	88.08	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	4.51

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

8 targets.

Target	Regulation
ASCL1
CPEB1	Unknown
DAB2IP
ELAC2
KDM6B
ME3
PINK1
XIST

Upstream regulators (CollecTRI, top): POU5F1, STAT3

miRNA regulators (miRDB)

37 targeting EED, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-4262	100.00	73.26	3931
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-4482-3P	99.98	72.50	3147
HSA-MIR-590-3P	99.96	74.34	6478
HSA-MIR-3910	99.95	71.13	2227
HSA-MIR-101-3P	99.94	75.03	2230
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-548E-5P	99.89	72.73	4486
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-4495	99.82	72.08	3080
HSA-MIR-323A-3P	99.79	70.30	1739
HSA-MIR-4645-3P	99.76	69.33	993
HSA-MIR-7-5P	99.67	70.53	1809
HSA-MIR-451B	99.55	68.28	1380
HSA-MIR-4672	99.50	71.58	2893
HSA-MIR-4728-3P	99.47	68.94	981
HSA-MIR-4735-5P	99.43	68.49	1780
HSA-MIR-513A-3P	99.39	70.63	3620
HSA-MIR-513C-3P	99.39	70.63	3620
HSA-MIR-190B-3P	99.33	68.29	1382
HSA-MIR-4293	99.22	65.46	1263
HSA-MIR-499A-3P	99.18	69.20	1392

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 23.5% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 37)

• EED is a nuclear factor and repressor of transcription and is recruited to the plasma membrane by HIV-1 nef (PMID:14759364)
• EED exerted an antiviral activity at the late stage of HIV-1 replication, which included genomic RNA packaging and virus assembly, resulting possibly from a mistrafficking of viral genomic RNA (gRNA) or gRNA/Gag complex. (PMID:17547741)
• NIPP1 is present in a complex with EED and EZH2 in vivo and has distinct binding sites for these proteins. (PMID:17804093)
• Identification of antibody-, MA-, IN- and EZH2-binding sites at EED’s surface provides a global picture of the immunogenic and protein-protein interacting regions in the EED C-terminal domain, organized as a seven-bladed beta-propeller protein. (PMID:18302803)
• histone modification including PRC2-mediated repressive histone marker H3K27me3 and active histone marker acH4 may involve in CD11b transcription during HL-60 leukemia cells reprogramming to terminal differentiation[polycomb repressive complex 2 ] (PMID:19578722)
• the carboxy-terminal domain of EED specifically binds to histone tails carrying trimethyl-lysine residues associated with repressive chromatin marks, and this leads to the allosteric activation of the methyltransferase activity of PRC2. (PMID:19767730)
• molecular basis of EED-methyllysine recognition, and the biochemical characterization of how the activity of a histone methyltransferase is oppositely regulated by two histone marks. (PMID:20974918)
• The authors found that Sox2 and Eed positively regulate each other’s expression and contribute to the maintenance of self-renewal in embryonic stem cells by controlling histone methylation and acetylation. (PMID:21540835)
• Promoter polymorphism of the EED gene is associated with the susceptibility to ulcerative colitis. (PMID:22271413)
• Genetic defects in PRC2 components other than EZH2 are not common in myeloid malignancies. (PMID:22308284)
• EED mutants impair polycomb repressive complex 2 and is associated with myelodysplastic syndrome and related neoplasms (PMID:22733077)
• These results suggest that the SNPs of the EED gene might not be associated with susceptibility to CRC. (PMID:23709348)
• Although inactivating mutations in PRC2-encoding genes EZH2, EED, and SUZ12 are present in T-cell acute lymphoblastic leukemia and in myeloid malignancies, gain-of-function mutations in EZH2 are frequently observed in B-cell lymphoma. (PMID:23982173)
• EZH2-EED is necessary and sufficient for binding to the lncRNA HOTAIR. (PMID:24320048)
• An integral role for EED as an epigenetic exchange factor coordinating the activities of PRC1 and 2, is reported. (PMID:24457600)
• Polycomb repressive complex 2 is recurrently inactivated through EED or SUZ12 loss in malignant peripheral nerve sheath tumors. (PMID:25240281)
• EED, a component of Polycomb repressive complex-2 (PRC2) that catalyzes methylation of lysine 27 of histone H3 (H3K27), was involved in epithelial-mesenchymal transition (EMT) of cancer cells induced by Transforming Growth Factor-beta (TGF-beta). (PMID:25264103)
• Data show that overall enhancer of zeste 2 (EZH2), embryonic ectoderm development (EED) and suppressor of zeste 12 homolog (SUZ12) expression in the colorectal cancer (CRC) tissues was significantly increased than in the non-cancerous tissue. (PMID:25326896)
• Mutations of SUZ12 and EED are reported to have tumor suppressive functions. (Review) (PMID:27000413)
• we have found two unrelated families of different ethnicities, with a similar rare phenotype, both associated with de novo mutations in this member of the PRC2 complex, we are confident that EED is indeed a novel overgrowth gene. (PMID:27193220)
• These findings support that Weaver syndrome is a disorder with locus heterogeneity and can be due to pathogenic variants in either EZH2 or EED. This case highlights the utility of exome sequencing as a clinical diagnostic tool for novel gene discovery as well as the importance of re-examination of exome data as new information about gene-disease associations becomes available. (PMID:27868325)
• we analyzed eight probands with clinically suspected Weaver syndrome by whole-exome sequencing and identified three mutations: a 25.4-kb deletion partially involving EZH2 and CUL1 ,a missense mutation , and a missense mutation in SUZ12 inherited from her father .In vitro functional analyses demonstrated that the identified EED and SUZ12 missense mutations cause decreased decreased trimethylation of lysine 27 of H3 (PMID:28229514)
• we present a patient with a clinical diagnosis of Weaver syndrome and novel de novo sequence variant in EED. Our observation together with previous reports [2, 3, 5] suggests that EED gene testing is warranted in patients with the overgrowth syndrome features and suspicion of Weaver syndrome with normal results for EZH2 gene sequencing. (PMID:29410511)
• Data suggest the polycomb repressive complex 2 subunits EZH2, SUZ12, and EED protein axis as promising therapeutic target for treating sarcoma. (PMID:29415665)
• These findings identify Eed/PRC2 as necessary for maintenance of global gene silencing and terminal differentiation in b cells, and suggest a ‘’two-hit’’ (chromatin and hyperglycemia) model of b cell dedifferentiation. (PMID:29754954)
• PICOT knock-down in Jurkat T cells resulted in a reduced histone H3 lysine 27 trimethylation (H3K27me3) at the PRC2 target gene, myelin transcription factor 1 (MYT1), suggesting that PICOT binding to EED alters PRC2-regulated transcriptional repression, and potentially contributes to the epigenetic regulation of chromatin silencing and remodeling. (PMID:30595380)
• Results report that EED presents a direct interaction with androgen receptor (AR). In the context of AR-positive prostate cancer, EED along with EZH2 regulate AR expression levels and its downstream targets. (PMID:30628724)
• Mutation in the EED gene is associated with Cohen-Gibson syndrome. (PMID:30793471)
• In silico modeling and calculations of the free energy changes resulting from these variants suggested that they not only destabilize the EED protein structure but also adversely affect interactions between EED, EZH2, and/or H3K27me3. (PMID:30858506)
• Identification of mutations in the PRC2 components EED and SUZ12 in the majority of MPNSTs may imply noncanonical oncogenic activities of the intact component, EZH2, and provide new opportunities for therapeutic intervention. (PMID:31023785)
• BR-001, a potent inhibitor of the EED subunit of the PRC2 complex, suppresses tumor progression by modulating the tumor microenvironment. (PMID:31395608)
• PICOT binding to chromatin-associated EED negatively regulates cyclin D2 expression by increasing H3K27me3 at the CCND2 gene promoter. (PMID:31527584)
• review the PRC2 complex and clinical syndromes of overgrowth and intellectual disability associated with core components EZH2, EED, and SUZ12 (PMID:31724824)
• Methylation of microRNA-338-5p by EED promotes METTL3-mediated translation of oncogene CDCP1 in gastric cancer. (PMID:33882457)
• Embryonic Ectoderm Development (EED) as a Novel Target for Cancer Treatment. (PMID:34544341)
• The PRC2 molecule EED is a target of epigenetic therapy for neuroblastoma. (PMID:35636260)
• EED related overgrowth: First report of multiple members in a single family. (PMID:37840385)

Cross-species orthologs

6 orthologs

Organism	Symbol	Gene ID
danio_rerio	eed	ENSDARG00000099640
mus_musculus	Eed	ENSMUSG00000030619
rattus_norvegicus	Eed	ENSRNOG00000017509
drosophila_melanogaster	esc	FBGN0000588
drosophila_melanogaster	escl	FBGN0032391
caenorhabditis_elegans		WBGENE00003224

Protein

Protein identifiers

Polycomb protein EED — O75530 (reviewed: O75530)

Alternative names: Embryonic ectoderm development protein, WD protein associating with integrin cytoplasmic tails 1

All UniProt accessions (6): O75530, A0A5F9ZI63, A0A9L9PY60, E9PJK2, E9PMU3, H0YEL4

UniProt curated annotations — full annotation on UniProt →

Function. Polycomb group (PcG) protein. Component of the PRC2/EED-EZH2 complex, which methylates ‘Lys-9’ and ‘Lys-27’ of histone H3, leading to transcriptional repression of the affected target gene. Also recognizes ‘Lys-26’ trimethylated histone H1 with the effect of inhibiting PRC2 complex methyltransferase activity on nucleosomal histone H3 ‘Lys-27’, whereas H3 ‘Lys-27’ recognition has the opposite effect, enabling the propagation of this repressive mark. The PRC2/EED-EZH2 complex may also serve as a recruiting platform for DNA methyltransferases, thereby linking two epigenetic repression systems. Genes repressed by the PRC2/EED-EZH2 complex include HOXC8, HOXA9, MYT1 and CDKN2A.

Subunit / interactions. Component of the PRC2/EED-EZH2 complex, which includes EED, EZH2, SUZ12, RBBP4 and RBBP7 and possibly AEBP2. The minimum components required for methyltransferase activity of the PRC2/EED-EZH2 complex are EED, EZH2 and SUZ12. Component of the PRC2/EED-EZH1 complex, which includes EED, EZH1, SUZ12, RBBP4 and AEBP2. The PRC2 complex may also interact with DNMT1, DNMT3A, DNMT3B and PHF1 via the EZH2 subunit and with SIRT1 via the SUZ12 subunit. Interacts with HDAC, HDAC2, histone H1 and YY1. May interact with ITGA4, ITGAE and ITGB7. Interacts with CDYL. Interacts with BMAL1. Interacts with KMT2A/MLL1. (Microbial infection) May interact with the MA protein of HIV-1.

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Expressed in brain, colon, heart, kidney, liver, lung, muscle, ovary, peripheral blood leukocytes, pancreas, placenta, prostate, spleen, small intestine, testis, thymus and uterus. Appears to be overexpressed in breast and colon cancer.

Post-translational modifications. Methylated. Binding to histone H1 ‘Lys-26’ promotes mono-, di-, and trimethylation of internal lysines.

Disease relevance. Cohen-Gibson syndrome (COGIS) [MIM:617561] An autosomal dominant overgrowth disorder characterized by accelerated osseous maturation, advanced bone age, skeletal abnormalities including flaring of the metaphyses of the long bones, large hands with long fingers and camptodactyly, scoliosis, cervical spine anomalies, dysmorphic facial features, and variable intellectual disability. The disease is caused by variants affecting the gene represented in this entry.

Domain organisation. The WD repeat domain mediates recognition of trimethylated histone peptides at the consensus sequence Ala-Arg-Lys-Ser. This is achieved through an aromatic cage encircling the methyllysine, and involving Phe-97, Tyr-148 and Tyr-365.

Induction. Expression is induced by E2F1, E2F2 and E2F3.

Similarity. Belongs to the WD repeat ESC family.

Isoforms (3)

UniProt ID	Names	Canonical?
O75530-1	1	yes
O75530-2	2
O75530-3	3

RefSeq proteins (3): NP_001294936, NP_001317263, NP_003788* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001680	WD40_rpt	Repeat
IPR015943	WD40/YVTN_repeat-like_dom_sf	Homologous_superfamily
IPR019775	WD40_repeat_CS	Conserved_site
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR051243	PcG_WD-repeat	Family

Pfam: PF00400

UniProt features (102 total): strand 40, modified residue 16, mutagenesis site 9, repeat 7, sequence variant 6, turn 6, helix 5, region of interest 4, sequence conflict 4, splice variant 2, initiator methionine 1, chain 1, compositionally biased region 1

Structure

Experimental structures (PDB)

78 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5U69	X-RAY DIFFRACTION	1.28
5U8F	X-RAY DIFFRACTION	1.34
5U8A	X-RAY DIFFRACTION	1.45
6SFB	X-RAY DIFFRACTION	1.52
3K26	X-RAY DIFFRACTION	1.58
5U5T	X-RAY DIFFRACTION	1.6
7QK4	X-RAY DIFFRACTION	1.6
7P3C	X-RAY DIFFRACTION	1.61
6V3Y	X-RAY DIFFRACTION	1.63
5U6D	X-RAY DIFFRACTION	1.64
6V3X	X-RAY DIFFRACTION	1.7
5TTW	X-RAY DIFFRACTION	1.74
7SI5	X-RAY DIFFRACTION	1.75
3K27	X-RAY DIFFRACTION	1.76
3IIW	X-RAY DIFFRACTION	1.8
5U5H	X-RAY DIFFRACTION	1.8
7QJG	X-RAY DIFFRACTION	1.8
7QJU	X-RAY DIFFRACTION	1.8
5K0M	X-RAY DIFFRACTION	1.83
6YVJ	X-RAY DIFFRACTION	1.84
6W7G	X-RAY DIFFRACTION	1.85
5H13	X-RAY DIFFRACTION	1.9
5H14	X-RAY DIFFRACTION	1.9
5H19	X-RAY DIFFRACTION	1.9
5U62	X-RAY DIFFRACTION	1.9
7MSB	X-RAY DIFFRACTION	1.9
7SI4	X-RAY DIFFRACTION	1.9
7P3J	X-RAY DIFFRACTION	1.93
3IJC	X-RAY DIFFRACTION	1.95
6SFC	X-RAY DIFFRACTION	2

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75530-F1	87.21	0.80

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Post-translational modifications (16): 2, 2, 34, 55, 66, 66, 66, 197, 197, 197, 268, 268, 268, 284, 284, 284

Mutagenesis-validated functional residues (9):

Position	Phenotype
97	abolishes binding to h3k27me3.
148	abolishes binding to h3k27me3.
193	impairs interaction with ezh2.
196	impairs interaction with ezh2.
300–301	impairs interaction with the matrix protein ma of hiv-1.
305–308	impairs interaction with the matrix protein ma of hiv-1.
364	abolishes binding to h3k27me3.
365	abolishes binding to h3k27me3.

Function

Pathways and Gene Ontology

Reactome pathways

10 pathways

ID	Pathway
R-HSA-212300	PRC2 methylates histones and DNA
R-HSA-2559580	Oxidative Stress Induced Senescence
R-HSA-3214841	PKMTs methylate histone lysines
R-HSA-5617472	Activation of anterior HOX genes in hindbrain development during early embryogenesis
R-HSA-8943724	Regulation of PTEN gene transcription
R-HSA-8953750	Transcriptional Regulation by E2F6
R-HSA-9609690	HCMV Early Events
R-HSA-9710421	Defective pyroptosis
R-HSA-9764725	Negative Regulation of CDH1 Gene Transcription
R-HSA-9909649	Regulation of PD-L1(CD274) transcription

MSigDB gene sets: 408 (showing top): GOBP_SPINAL_CORD_DEVELOPMENT, E2F_Q4, WANG_CLIM2_TARGETS_UP, PAX4_01, TGCGCANK_UNKNOWN, E2F4DP1_01, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_RESPONSE_TO_PEPTIDE, SP3_Q3, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_UP, GOBP_NEUROGENESIS, BROWNE_HCMV_INFECTION_16HR_UP, GNF2_MCM5, PUJANA_CHEK2_PCC_NETWORK, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS

GO Biological Process (10): negative regulation of transcription by RNA polymerase II (GO:0000122), spinal cord development (GO:0021510), heterochromatin formation (GO:0031507), negative regulation of DNA-templated transcription (GO:0045892), oligodendrocyte differentiation (GO:0048709), genomic imprinting (GO:0071514), facultative heterochromatin formation (GO:0140718), cellular response to leukemia inhibitory factor (GO:1990830), regulation of adaxial/abaxial pattern formation (GO:2000011), chromatin organization (GO:0006325)

GO Molecular Function (6): transcription corepressor binding (GO:0001222), chromatin binding (GO:0003682), enzyme activator activity (GO:0008047), identical protein binding (GO:0042802), protein binding (GO:0005515), nucleosome binding (GO:0031491)

GO Cellular Component (8): sex chromatin (GO:0001739), nucleus (GO:0005634), nucleoplasm (GO:0005654), chromatin silencing complex (GO:0005677), cytosol (GO:0005829), ESC/E(Z) complex (GO:0035098), pronucleus (GO:0045120), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-10 pathways:

Category	Pathways
Epigenetic regulation of gene expression	1
Cellular Senescence	1
Chromatin modifying enzymes	1
Activation of HOX genes during differentiation	1
PTEN Regulation	1
Generic Transcription Pathway	1
HCMV Infection	1
Diseases of programmed cell death	1
Regulation of CDH1 Gene Transcription	1
Regulation of PD-L1(CD274) expression	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
central nervous system development	2
binding	2
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
anatomical structure development	1
cellular component assembly	1
heterochromatin boundary formation	1
negative regulation of gene expression, epigenetic	1
heterochromatin organization	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
glial cell differentiation	1
germ cell development	1
epigenetic programming of gene expression	1
heterochromatin formation	1
cellular response to cytokine stimulus	1
response to leukemia inhibitory factor	1
adaxial/abaxial pattern specification	1
regulation of multicellular organismal process	1
cellular component organization	1
transcription coregulator binding	1
catalytic activity	1
enzyme regulator activity	1
molecular function activator activity	1
protein binding	1
chromatin binding	1
protein-containing complex binding	1
heterochromatin	1
sex chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
nuclear protein-containing complex	1
cytoplasm	1
PcG protein complex	1
histone methyltransferase complex	1
nucleus	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

2884 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
EED	SUZ12	Q15022	999
EED	EZH2	Q15910	999
EED	RBBP4	P31149	997
EED	EZH1	Q92800	997
EED	RBBP7	Q16576	996
EED	JARID2	Q92833	993
EED	AEBP2	Q6ZN18	952
EED	RNF2	Q99496	950
EED	H3-3A	P06351	891
EED	H3C14	Q71DI3	891
EED	H3C1	P02295	891
EED	PHC1	P78364	891
EED	H3-4	Q16695	891
EED	H3-7	Q5TEC6	891
EED	H3-5	Q6NXT2	891

IntAct

185 interactions, top by confidence:

A	B	Type	Score
EZH2	EED	psi-mi:“MI:0915”(physical association)	0.930
EZH2	EED	psi-mi:“MI:0914”(association)	0.930
EED	EZH2	psi-mi:“MI:0915”(physical association)	0.930
SUZ12	EED	psi-mi:“MI:0914”(association)	0.910
SUZ12	EED	psi-mi:“MI:0915”(physical association)	0.910
EZH2	PHF1	psi-mi:“MI:0914”(association)	0.900
EED	RBBP4	psi-mi:“MI:0914”(association)	0.840
RBBP7	CDK2AP1	psi-mi:“MI:0914”(association)	0.840
PHF1	EED	psi-mi:“MI:0914”(association)	0.790
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
EZH1	EED	psi-mi:“MI:0915”(physical association)	0.740
EZH2	EPOP	psi-mi:“MI:0914”(association)	0.730
PHF19	EED	psi-mi:“MI:0914”(association)	0.730
RBBP7	HAT1	psi-mi:“MI:0914”(association)	0.730

BioGRID (1023): EED (Affinity Capture-MS), EED (Affinity Capture-MS), EED (Affinity Capture-Western), EED (Affinity Capture-Western), EED (Affinity Capture-Western), EED (Affinity Capture-MS), EED (Affinity Capture-MS), EED (Affinity Capture-MS), RNF2 (Affinity Capture-MS), BMI1 (Affinity Capture-MS), FBXO11 (Affinity Capture-MS), SNRNP70 (Affinity Capture-MS), RING1 (Affinity Capture-MS), CBX8 (Affinity Capture-MS), SNRPA (Affinity Capture-MS)

ESM2 similar proteins: A8Q2R5, A8XSW2, B0X2V9, B3MET8, B3NSK1, B4GIJ0, B4HND9, B4J8H6, B4KRQ4, B4MFM2, B4P7H8, B4QB64, O16023, O75530, P49846, Q05B17, Q0WV90, Q16MY0, Q1LZ08, Q20059, Q24338, Q28YY2, Q2TAF3, Q2TAY7, Q2TBS9, Q32PG3, Q3SZ25, Q3UKJ7, Q4R2Z6, Q5F3K4, Q5NBT9, Q5RAW8, Q5ZME8, Q6CKE8, Q6DIP5, Q6NNP0, Q6NRT3, Q6P4J8, Q6PFM9, Q6S7B0

Diamond homologs: A0A223GEB2, A0DB19, A3LNI7, A4R2Q6, A5DJX5, A5DXE2, A6S0T8, A7ECP3, A7RHG8, B0LSW3, B3S4I5, B4GAJ1, B4KT48, B5X3C4, B5X3Z6, B7PS00, B9WD30, C3XVT5, C4Q0P6, C4R6H3, C4YPI7, C5MJE8, E3LB80, G4MQX3, O54927, O54929, O75530, O88342, P07834, P25382, P38011, P43033, P43034, P46800, P61480, P63004, P63005, Q0V8J1, Q0VC24, Q10282

SIGNOR signaling

2 interactions.

A	Effect	B	Mechanism
EED	“form complex”	SUZ12/EED	binding
EED	“form complex”	“Polycomb repressive complex 2”	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 106 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
SUMOylation of DNA methylation proteins	5	44.8×	5e-06
Transcriptional Regulation by E2F6	8	31.2×	2e-08
PRC2 methylates histones and DNA	15	30.4×	3e-16
Regulation of PTEN gene transcription	10	23.8×	2e-09
Defective pyroptosis	9	18.8×	1e-07
Negative Regulation of CDH1 Gene Transcription	9	14.4×	1e-06
PKMTs methylate histone lysines	6	12.9×	3e-04
Interaction of NuRD complexes with transcription factors	7	11.8×	1e-04

GO biological processes:

GO term	Partners	Fold	FDR
DNA methylation-dependent constitutive heterochromatin formation	8	47.3×	4e-09
negative regulation of gene expression, epigenetic	8	34.9×	2e-08
stem cell differentiation	6	19.6×	6e-05
heterochromatin formation	7	19.4×	9e-06
rhythmic process	7	19.1×	9e-06
cellular response to amino acid stimulus	5	16.6×	9e-04
regulation of circadian rhythm	5	14.1×	2e-03
chromatin organization	10	10.8×	7e-06

Disease & clinical

Clinical variants and AI predictions

ClinVar

177 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	5
Likely pathogenic	8
Uncertain significance	75
Likely benign	38
Benign	33

Top pathogenic / likely-pathogenic (13)

Variant ID	HGVS	Classification
2848299	NM_003797.5(EED):c.923A>G (p.Tyr308Cys)	Pathogenic
430644	NM_003797.5(EED):c.772C>T (p.His258Tyr)	Pathogenic
430645	NM_003797.5(EED):c.904A>G (p.Arg302Gly)	Pathogenic
430646	NM_003797.5(EED):c.707G>C (p.Arg236Thr)	Pathogenic
560087	Single allele	Pathogenic
1700087	NM_003797.5(EED):c.1241G>A (p.Arg414Gln)	Likely pathogenic
2429866	NM_003797.5(EED):c.767T>C (p.Met256Thr)	Likely pathogenic
3572541	NM_003797.5(EED):c.282A>C (p.Gln94His)	Likely pathogenic
3765780	NM_003797.5(EED):c.773A>T (p.His258Leu)	Likely pathogenic
430643	NM_003797.5(EED):c.906A>C (p.Arg302Ser)	Likely pathogenic
4531366	NM_003797.5(EED):c.710A>G (p.Asp237Gly)	Likely pathogenic
584435	NM_003797.5(EED):c.1097T>C (p.Met366Thr)	Likely pathogenic
802712	NM_003797.5(EED):c.1133C>T (p.Ala378Val)	Likely pathogenic

SpliceAI

1851 predictions. Top by Δscore:

Variant	Effect	Δscore
11:86245340:GAAT:G	donor_gain	1.0000
11:86245344:G:GG	donor_gain	1.0000
11:86250372:G:GT	donor_gain	1.0000
11:86250400:G:GT	donor_gain	1.0000
11:86252239:GA:G	donor_gain	1.0000
11:86252241:G:GG	donor_gain	1.0000
11:86255216:CATTA:C	acceptor_loss	1.0000
11:86255218:TTA:T	acceptor_loss	1.0000
11:86255219:TAGGT:T	acceptor_loss	1.0000
11:86255288:G:GG	donor_gain	1.0000
11:86257513:A:AG	acceptor_gain	1.0000
11:86257514:G:GG	acceptor_gain	1.0000
11:86257514:GCACT:G	acceptor_gain	1.0000
11:86264259:GTGCT:G	donor_gain	1.0000
11:86264264:G:GG	donor_gain	1.0000
11:86276972:T:A	acceptor_gain	1.0000
11:86276978:A:AC	acceptor_loss	1.0000
11:86276978:A:AG	acceptor_gain	1.0000
11:86276979:G:GG	acceptor_gain	1.0000
11:86276979:GT:G	acceptor_gain	1.0000
11:86276979:GTC:G	acceptor_gain	1.0000
11:86276979:GTCT:G	acceptor_gain	1.0000
11:86276979:GTCTT:G	acceptor_gain	1.0000
11:86277136:AAG:A	donor_loss	1.0000
11:86277137:AG:A	donor_loss	1.0000
11:86277138:GGTA:G	donor_loss	1.0000
11:86277139:GT:G	donor_loss	1.0000
11:86277594:A:G	acceptor_gain	1.0000
11:86277987:GCCAA:G	donor_gain	1.0000
11:86277988:CCAAG:C	donor_loss	1.0000

AlphaMissense

2973 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:86252169:T:A	F97I	1.000
11:86252169:T:C	F97L	1.000
11:86252170:T:C	F97S	1.000
11:86252170:T:G	F97C	1.000
11:86252171:T:A	F97L	1.000
11:86252171:T:G	F97L	1.000
11:86252172:G:A	G98R	1.000
11:86252172:G:C	G98R	1.000
11:86252173:G:A	G98E	1.000
11:86252221:C:A	A114E	1.000
11:86252229:G:A	G117R	1.000
11:86252229:G:C	G117R	1.000
11:86252230:G:A	G117E	1.000
11:86252230:G:T	G117V	1.000
11:86255223:T:A	V121D	1.000
11:86255231:T:G	Y124D	1.000
11:86256402:T:G	Y148D	1.000
11:86256410:T:G	C150W	1.000
11:86256414:T:A	W152R	1.000
11:86256414:T:C	W152R	1.000
11:86256416:G:C	W152C	1.000
11:86256416:G:T	W152C	1.000
11:86256448:T:C	L163P	1.000
11:86256451:C:A	A164D	1.000
11:86256457:C:A	A166D	1.000
11:86256459:G:A	G167R	1.000
11:86256459:G:C	G167R	1.000
11:86256460:G:A	G167E	1.000
11:86256460:G:T	G167V	1.000
11:86256469:G:A	G170D	1.000

dbSNP variants (sampled 300 via entrez): RS1000025209 (11:86267800 A>C,G), RS1000070799 (11:86281218 T>C), RS1000112460 (11:86249456 C>A,G,T), RS1000307968 (11:86244500 A>G), RS1000345066 (11:86261476 C>T), RS1000372437 (11:86261459 G>A), RS1000383381 (11:86281562 T>C), RS1000414420 (11:86281764 T>C), RS1000443713 (11:86267551 G>A), RS1000475125 (11:86267828 T>C,G), RS1000645462 (11:86243346 G>C,T), RS1000716094 (11:86247860 G>A), RS1000720811 (11:86261729 G>C), RS1000745989 (11:86280283 G>A), RS1000864823 (11:86243023 T>C)

Disease associations

OMIM: gene MIM:605984 | disease phenotypes: MIM:617561, MIM:133780

GenCC curated gene-disease

Disease	Classification	Inheritance
Cohen-Gibson syndrome	Strong	Autosomal dominant
Weaver syndrome	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

Expert-panel classifications — Definitive > Strong > Moderate > Limited > Disputed > Refuted.

Disease	Classification	Inheritance
Cohen-Gibson syndrome	Moderate	AD

Mondo (5): Cohen-Gibson syndrome (MONDO:0060510), autism spectrum disorder (MONDO:0005258), exudative vitreoretinopathy 1 (MONDO:0007589), hereditary breast ovarian cancer syndrome (MONDO:0003582), Weaver syndrome (MONDO:0010193)

Orphanet (5): Cohen-Gibson syndrome (Orphanet:659396), Familial exudative vitreoretinopathy (Orphanet:891), Retinopathy of prematurity (Orphanet:90050), Hereditary breast and/or ovarian cancer syndrome (Orphanet:145), NON RARE IN EUROPE: Autism (Orphanet:106)

HPO phenotypes

47 total (30 of 47 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000028	Cryptorchidism
HP:0000098	Tall stature
HP:0000256	Macrocephaly
HP:0000278	Retrognathia
HP:0000286	Epicanthus
HP:0000311	Round face
HP:0000316	Hypertelorism
HP:0000337	Broad forehead
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000431	Wide nasal bridge
HP:0000494	Downslanted palpebral fissures
HP:0000508	Ptosis
HP:0000518	Cataract
HP:0000545	Myopia
HP:0000750	Delayed speech and language development
HP:0000938	Osteopenia
HP:0000995	Melanocytic nevus
HP:0001176	Large hands
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001263	Global developmental delay
HP:0001288	Gait disturbance
HP:0001290	Generalized hypotonia
HP:0001371	Flexion contracture
HP:0001382	Joint hypermobility
HP:0001537	Umbilical hernia
HP:0001548	Overgrowth
HP:0001643	Patent ductus arteriosus

GWAS associations

3 associations (top):

Study	Trait	p-value
GCST007327_154	Smoking status (ever vs never smokers)	7.000000e-09
GCST008810_36	Smoking initiation (ever regular vs never regular)	7.000000e-10
GCST010002_244	Refractive error	2.000000e-53

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0004318	smoking behavior
EFO:0005670	smoking initiation

MeSH disease descriptors (3)

Descriptor	Name	Tree numbers
D061325	Hereditary Breast and Ovarian Cancer Syndrome	C04.588.180.483; C04.588.322.455.431; C04.700.517; C12.050.351.500.056.630.705.431; C12.050.351.937.418.685.431; C12.100.250.056.630.705.431; C12.900.418.685.431; C16.320.700.517; C17.800.090.500.483; C19.344.410.431; C19.391.630.705.431
C536382	Exudative vitreoretinopathy 1 (supp.)
C536687	Weaver syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (10): CHEMBL2189117 (SINGLE PROTEIN), CHEMBL3137286 (PROTEIN COMPLEX), CHEMBL3137287 (PROTEIN COMPLEX), CHEMBL3301388 (PROTEIN COMPLEX), CHEMBL4748218 (PROTEIN-PROTEIN INTERACTION), CHEMBL6066052 (PROTEIN-PROTEIN INTERACTION), CHEMBL6066550 (PROTEIN COMPLEX), CHEMBL6066551 (PROTEIN COMPLEX), CHEMBL6066587 (PROTEIN COMPLEX), CHEMBL6195581 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 47,654 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL296419	ASTEMIZOLE	4	21,577
CHEMBL3414621	TAZEMETOSTAT	4	1,869
CHEMBL297453	EPIGALOCATECHIN GALLATE	3	22,804
CHEMBL6067682	POCIREDIR	2	8
CHEMBL3287735	GSK2816126	1	1,396

PharmGKB: 1 entry (VIP=true, CPIC=false)

GtoPdb / IUPHAR curated pharmacology

(IUPHAR/BPS Guide to Pharmacology — expert-curated)

Target class: enzyme — Neutral sphingomyelinase coupling factors

Most potent curated ligand interactions (4 total), top 4:

Ligand	Action	Affinity	Parameter
A-395	Binding	9.4	pKi
AZ14117230	Binding	9.27	pKd
pociredir	Negative	8.6	pKd
MAK683	Negative	8.24	pIC50

Binding affinities (BindingDB)

342 measured of 397 human assays (397 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
8-(2,5-dimethylpyrazol-3-yl)-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	0.9 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
(3R,4S)-1-[(1S)-7-fluoroindan-1-yl]-N,N-dimethyl-4-(1-methylindol-3-yl)pyrrolidin-3-amine (3)	KI	1 nM
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(1-oxidopyridin-1-ium-3-yl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	1 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
[5-[5-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylamino]-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl]-4-methyl-2-pyridinyl]-pyrrolidin-1-ylmethanone	IC50	1.3 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
8-[6-[(dimethylamino)methyl]-2-methyl-3-pyridinyl]-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	1.4 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-imidazol-1-yl-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	1.4 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
8-(6-ethyl-4-methyl-3-pyridinyl)-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	1.5 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(2-methyl-6-methylsulfonyl-3-pyridinyl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	1.6 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
[5-[5-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylamino]-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl]-2-pyridinyl]-pyrrolidin-1-ylmethanone	IC50	1.9 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
8-(4-chloro-6-methoxy-3-pyridinyl)-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	1.9 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(3-methyl-1-propan-2-ylpyrazol-4-yl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	2.1 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(5-methyl-1-propan-2-ylpyrazol-4-yl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	2.3 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(6-methoxy-3-pyridinyl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	2.4 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
8-(2,5-dimethyl-4-pyridinyl)-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	2.4 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-[2-(fluoromethyl)-3-methyl-4-pyridinyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	2.5 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(2-methyl-3-pyridinyl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	2.6 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(4-methyl-6-methylsulfonyl-3-pyridinyl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	2.6 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
8-[2-(difluoromethyl)-3-methyl-4-pyridinyl]-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	2.6 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
8-(6-ethyl-2-methyl-3-pyridinyl)-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	2.7 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(6-methoxy-4-methyl-3-pyridinyl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	2.9 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
8-(2-cyclopropyl-4-methylpyrimidin-5-yl)-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	2.9 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(2-methylpyrazol-3-yl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	2.9 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
8-[3-(difluoromethyl)-1-methylpyrazol-4-yl]-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	3 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
8-(2,6-dimethyl-3-pyridinyl)-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	3.3 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
8-(2,4-dimethylpyrimidin-5-yl)-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	3.4 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(2-methoxy-4-methylpyrimidin-5-yl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	3.4 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(4-methyl-2-propan-2-yloxypyrimidin-5-yl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	3.5 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
(2R)-1-[4-[5-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylamino]-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl]-3,5-dimethylpyrazol-1-yl]propan-2-ol	IC50	3.5 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(4-fluoro-6-methoxy-3-pyridinyl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	3.6 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
8-[2-(difluoromethyl)-6-methyl-3-pyridinyl]-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	3.6 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
8-(6-cyclopropyl-2-methyl-3-pyridinyl)-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	3.8 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
8-(2,3-dimethyl-4-pyridinyl)-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	3.8 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
8-(2-ethoxy-4-methylpyrimidin-5-yl)-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	3.9 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
rac-(3R,4S)-1-(2-fluoro-6-methylbenzyl)-N,N-dimethyl-4-(1-methyl-1H-indol-3-yl)pyrrolidin-3-amine (2)	KI	4 nM
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(2-methoxypyrimidin-5-yl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	4.2 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
2-[4-[5-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylamino]-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl]-5-methylpyrazol-1-yl]ethanol	IC50	4.2 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
5-[5-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylamino]-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl]-N,N,6-trimethylpyridine-2-carboxamide	IC50	4.2 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
8-(1,5-dimethylpyrazol-4-yl)-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	4.4 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-[2-(trifluoromethyl)-4-pyridinyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	4.4 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(4-fluoro-2-methylphenyl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	4.5 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(4-methylpyrimidin-5-yl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	4.6 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(2-methyl-4-pyridinyl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	4.7 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
[3-[5-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylamino]-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl]-2-pyridinyl]methanol	IC50	4.8 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-[4-(1-pyrrolidin-1-ylethyl)phenyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	4.8 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
US10793549, Compound G-63	IC50	5 nM	US-10793549: Sulfuryl-substituted benzoheterocyclic derivative, preparation method and medical use thereof
2-[4-[5-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylamino]-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl]-3,5-dimethylpyrazol-1-yl]ethanol	IC50	5.1 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
N-(2,3-dihydro-1-benzofuran-4-ylmethyl)-8-(2-methylpyrazol-3-yl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	5.5 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
[4-[5-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylamino]-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl]-1-methylpyrazol-5-yl]methanol	IC50	6.1 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
8-[4-[(dimethylamino)methyl]phenyl]-N-[(5-fluoro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	6.5 nM	US-9580437: Triazolopyrimidine compounds and uses thereof
8-(4-chloro-3-pyridinyl)-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	IC50	10 nM	US-9580437: Triazolopyrimidine compounds and uses thereof

ChEMBL bioactivities

2991 potent at pChembl≥5 of 3026 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	IC50	0.1	nM	CHEMBL4159112
9.70	IC50	0.2	nM	CHEMBL4637520
9.70	IC50	0.2	nM	CHEMBL4637096
9.70	IC50	0.2	nM	CHEMBL4870920
9.61	Kd	0.2455	nM	CHEMBL4755687
9.54	Ki	0.29	nM	CHEMBL4060827
9.52	Ki	0.3	nM	CHEMBL4093096
9.52	Ki	0.3	nM	CHEMBL4084398
9.52	Ki	0.3	nM	CHEMBL4104741
9.52	IC50	0.3	nM	CHEMBL4638412
9.52	Ki	0.3	nM	CHEMBL5181703
9.51	Ki	0.31	nM	CHEMBL4104741
9.49	Kd	0.32	nM	CHEMBL5289498
9.40	IC50	0.4	nM	CHEMBL4161265
9.40	IC50	0.4	nM	CHEMBL4645324
9.40	IC50	0.4	nM	CHEMBL4643880
9.40	IC50	0.4	nM	CHEMBL4645310
9.40	IC50	0.4	nM	CHEMBL4644746
9.40	IC50	0.4	nM	CHEMBL4865691
9.40	Ki	0.4	nM	CHEMBL4104741
9.35	Ki	0.45	nM	CHEMBL4076017
9.30	IC50	0.5	nM	CHEMBL4165937
9.30	IC50	0.5	nM	CHEMBL4635558
9.30	IC50	0.5	nM	CHEMBL4642335
9.30	IC50	0.5	nM	CHEMBL4851576
9.27	Kd	0.537	nM	CHEMBL4779022
9.27	Kd	0.537	nM	CHEMBL5275319
9.22	Ki	0.6	nM	CHEMBL2204997
9.22	IC50	0.6	nM	CHEMBL4160111
9.22	IC50	0.6	nM	CHEMBL4872891
9.22	IC50	0.6	nM	CHEMBL4869420
9.22	IC50	0.6	nM	CHEMBL4877375
9.22	IC50	0.6	nM	CHEMBL4860499
9.22	IC50	0.6	nM	CHEMBL4645324
9.20	Kd	0.631	nM	CHEMBL5180485
9.19	Ki	0.65	nM	CHEMBL4073166
9.15	Ki	0.7	nM	CHEMBL4060827
9.15	IC50	0.7	nM	CHEMBL4640949
9.15	IC50	0.7	nM	CHEMBL4873268
9.15	IC50	0.7	nM	CHEMBL4861749
9.15	IC50	0.7	nM	CHEMBL4859559
9.15	IC50	0.7	nM	CHEMBL4850823
9.15	IC50	0.7	nM	CHEMBL6016384
9.13	Ki	0.74	nM	CHEMBL4065766
9.10	IC50	0.8	nM	CHEMBL4172576
9.10	IC50	0.8	nM	CHEMBL4640556
9.10	IC50	0.8	nM	CHEMBL4862163
9.10	IC50	0.8	nM	CHEMBL4856280
9.10	IC50	0.8	nM	CHEMBL4878932
9.05	IC50	0.9	nM	CHEMBL4649099

PubChem BioAssay actives

634 with measured affinity, of 800 total; 50 most potent distinct compounds. Largely complementary to BindingDB; screening values are coarse (µM, 4 dp), so sub-nM hits tie at the floor.

Compound	Assay	Type	Value	Unit
5-ethyl-6-[ethyl(oxan-4-yl)amino]-N-[(4-methoxy-6-methyl-2-oxo-1H-pyridin-3-yl)methyl]-2-[(4-methylpiperazin-1-yl)methyl]-1-benzofuran-4-carboxamide	1350244: Inhibition of human N-terminal His-tagged EZH2/flag-tagged EED/SUZ12/AEBP2/RBAP48 A677G mutant (2 to end residues) expressed in baculovirus infected Sf9 insect cells using histone H3 (1 to 50 residues)-GGK as substrate after 2 hrs in presence of SAM by fluorescence assay	ic50	0.0001	uM
8-(6-cyclopropyl-3-pyridinyl)-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-1-methylsulfonylimidazo[1,5-c]pyrimidin-5-amine	1652813: Inhibition of EED ( 1 to 441 residues) (unknown origin) pre-incubated for 15 mins before biotin-H3K27me3 (19 to 33 residues) addition and further incubated for 30 mins by AlphaScreen.based EED-H3K27me3 peptide competition binding assay	ic50	0.0002	uM
8-[6-(difluoromethyl)-3-pyridinyl]-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-1-methylsulfonylimidazo[1,5-c]pyrimidin-5-amine	1652813: Inhibition of EED ( 1 to 441 residues) (unknown origin) pre-incubated for 15 mins before biotin-H3K27me3 (19 to 33 residues) addition and further incubated for 30 mins by AlphaScreen.based EED-H3K27me3 peptide competition binding assay	ic50	0.0002	uM
3-[5-[5-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylamino]-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl]-6-methyl-2-pyridinyl]-N-methylpropanamide	1928070: Binding affinity to PRC2 catalytic core EED (unknown origin) by surface plasmon resonance assay	kd	0.0002	uM
15-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylimino]-9-propan-2-yl-5-(trifluoromethyl)-4,9,12,14,16-pentazatetracyclo[9.6.1.02,7.014,18]octadeca-1(17),2,4,6,12-pentaen-10-one	1769306: Inhibition of biotinylated H3K27Me3 peptide (19 to 33 residues) binding to His-tagged EED (1 to 441 residues) (unknown origin) preincubated for 15 mins followed by H3K27Me3 addition and measured after 30 mins by alphascreen competition binding assay	ic50	0.0002	uM
(3R,4S)-1-(7-fluoro-2,3-dihydro-1H-inden-1-yl)-N,N-dimethyl-4-[4-(4-methylsulfonylpiperazin-1-yl)phenyl]pyrrolidin-3-amine	1452116: Binding affinity to GST tagged EED (unknown origin) after 1 hr by OG(488) probe based TR-FRET assay	ki	0.0003	uM
1-[4-[4-[(3S,4R)-4-(dimethylamino)-1-(7-fluoro-2,3-dihydro-1H-inden-1-yl)pyrrolidin-3-yl]phenyl]piperazin-1-yl]ethanone	1439668: Inhibition of OG(488) labeled probe binding to GST-tagged EED (unknown origin) after 1 hr by LanthaScreen TR-FRET assay	ki	0.0003	uM
1-[4-[4-[(3S,4R)-4-(dimethylamino)-1-[(1S)-7-fluoro-2,3-dihydro-1H-inden-1-yl]pyrrolidin-3-yl]phenyl]piperazin-1-yl]ethanone	1452116: Binding affinity to GST tagged EED (unknown origin) after 1 hr by OG(488) probe based TR-FRET assay	ki	0.0003	uM
(3S,4R)-1-(7-fluoro-2,3-dihydro-1H-inden-1-yl)-N,N-dimethyl-4-[4-(4-methylsulfonylpiperazin-1-yl)phenyl]pyrrolidin-3-amine	1872371: Binding affinity to GST-tagged EED (unknown origin) assessed as inhibition constant incubated for 1 hr by TR-FRET assay	ki	0.0003	uM
trans-(1S,2R)-4-(7-fluoro-2,3-dihydro-1H-inden-1-yl)-N,N-dimethyl-2-[4-(4-methylsulfonylpiperazin-1-yl)phenyl]cyclopentan-1-amine	1439668: Inhibition of OG(488) labeled probe binding to GST-tagged EED (unknown origin) after 1 hr by LanthaScreen TR-FRET assay	ki	0.0003	uM
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-1-methylsulfonyl-8-[6-(trifluoromethyl)-3-pyridinyl]imidazo[1,5-c]pyrimidin-5-amine	1652813: Inhibition of EED ( 1 to 441 residues) (unknown origin) pre-incubated for 15 mins before biotin-H3K27me3 (19 to 33 residues) addition and further incubated for 30 mins by AlphaScreen.based EED-H3K27me3 peptide competition binding assay	ic50	0.0003	uM
(4S)-4-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S,3S)-2-[[(2S)-2-[[(2S,3R)-2-[[(2S)-2-[[(2S,8S,11S,15E,20S)-20-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-[[(2S)-2-acetamido-3-phenylpropanoyl]amino]-3-hydroxypropanoyl]amino]-3-hydroxypropanoyl]amino]-4-amino-4-oxobutanoyl]amino]-5-carbamimidamidopentanoyl]amino]-2-(4-aminobutyl)-5-[(2S)-butan-2-yl]-11,20-dimethyl-8-(2-methylpropyl)-3,6,9,21-tetraoxo-1,4,7,10-tetrazacyclohenicos-15-ene-11-carbonyl]amino]-5-carbamimidamidopentanoyl]amino]-3-hydroxybutanoyl]amino]-5-amino-5-oxopentanoyl]amino]-3-methylpentanoyl]amino]-4-methylpentanoyl]amino]-4-amino-4-oxobutanoyl]amino]-5-amino-5-oxopentanoyl]amino]-5-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-5-amino-1-[[(2S)-1-[[(2S)-1-[[(2S,3S)-1-[[(2S)-5-amino-1-[(2S)-2-[[(1S)-1-carboxy-2-methylpropyl]carbamoyl]pyrrolidin-1-yl]-1,5-dioxopentan-2-yl]amino]-3-methyl-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-5-carbamimidamido-1-oxopentan-2-yl]amino]-1,5-dioxopentan-2-yl]amino]-1-oxohexan-2-yl]amino]-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-5-oxopentanoic acid	1934289: Binding affinity to C-terminal histidine tagged EED (unknown origin) expressed in Escherichia coli BL21(DE3) incubated for 15 mins by fluorescence polarization analysis	kd	0.0003	uM
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(2-methyl-3-pyridinyl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	1872356: Binding affinity to EED (unknown origin) assessed as dissociation constant by SPR analysis	kd	0.0004	uM
6-[4-[(3S,4R)-4-(dimethylamino)-1-(7-fluoro-2,3-dihydro-1H-inden-1-yl)pyrrolidin-3-yl]piperidin-1-yl]pyridine-3-carboxamide	1439668: Inhibition of OG(488) labeled probe binding to GST-tagged EED (unknown origin) after 1 hr by LanthaScreen TR-FRET assay	ki	0.0004	uM
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-1-methylsulfonyl-8-(4-methylsulfonylphenyl)imidazo[1,5-c]pyrimidin-5-amine	1652813: Inhibition of EED ( 1 to 441 residues) (unknown origin) pre-incubated for 15 mins before biotin-H3K27me3 (19 to 33 residues) addition and further incubated for 30 mins by AlphaScreen.based EED-H3K27me3 peptide competition binding assay	ic50	0.0004	uM
2-chloro-6-[ethyl(oxan-4-yl)amino]-N-[(4-methoxy-6-methyl-2-oxo-1H-pyridin-3-yl)methyl]-5-methyl-1-benzofuran-4-carboxamide	1350244: Inhibition of human N-terminal His-tagged EZH2/flag-tagged EED/SUZ12/AEBP2/RBAP48 A677G mutant (2 to end residues) expressed in baculovirus infected Sf9 insect cells using histone H3 (1 to 50 residues)-GGK as substrate after 2 hrs in presence of SAM by fluorescence assay	ic50	0.0004	uM
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(4-fluorophenyl)-1-methylsulfonylimidazo[1,5-c]pyrimidin-5-amine	1652813: Inhibition of EED ( 1 to 441 residues) (unknown origin) pre-incubated for 15 mins before biotin-H3K27me3 (19 to 33 residues) addition and further incubated for 30 mins by AlphaScreen.based EED-H3K27me3 peptide competition binding assay	ic50	0.0004	uM
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-1-methylsulfonyl-8-[2-methyl-6-(trifluoromethyl)-3-pyridinyl]imidazo[1,5-c]pyrimidin-5-amine	1652813: Inhibition of EED ( 1 to 441 residues) (unknown origin) pre-incubated for 15 mins before biotin-H3K27me3 (19 to 33 residues) addition and further incubated for 30 mins by AlphaScreen.based EED-H3K27me3 peptide competition binding assay	ic50	0.0004	uM
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(6-methyl-3-pyridinyl)-1-methylsulfonylimidazo[1,5-c]pyrimidin-5-amine	1652813: Inhibition of EED ( 1 to 441 residues) (unknown origin) pre-incubated for 15 mins before biotin-H3K27me3 (19 to 33 residues) addition and further incubated for 30 mins by AlphaScreen.based EED-H3K27me3 peptide competition binding assay	ic50	0.0004	uM
14-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylimino]-5-methyl-4,5,8,11,13,15-hexazatetracyclo[8.6.1.02,6.013,17]heptadeca-1(16),2(6),3,11-tetraen-9-one	1769306: Inhibition of biotinylated H3K27Me3 peptide (19 to 33 residues) binding to His-tagged EED (1 to 441 residues) (unknown origin) preincubated for 15 mins followed by H3K27Me3 addition and measured after 30 mins by alphascreen competition binding assay	ic50	0.0004	uM
(2S,4R)-1-[(2S)-2-[5-[3-[5-[5-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylamino]-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl]-6-methyl-2-pyridinyl]propanoylamino]pentanoylamino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1872403: Binding affinity to human N-terminal His-6 tagged EED expressed in Escherichia coli strain BL2(DE3) by SPR analysis	kd	0.0005	uM
2-cyclopropyl-6-[ethyl(oxan-4-yl)amino]-N-[(4-methoxy-6-methyl-2-oxo-1H-pyridin-3-yl)methyl]-5-methyl-1-benzofuran-4-carboxamide	1350244: Inhibition of human N-terminal His-tagged EZH2/flag-tagged EED/SUZ12/AEBP2/RBAP48 A677G mutant (2 to end residues) expressed in baculovirus infected Sf9 insect cells using histone H3 (1 to 50 residues)-GGK as substrate after 2 hrs in presence of SAM by fluorescence assay	ic50	0.0005	uM
8-(2,6-dimethyl-3-pyridinyl)-N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-1-methylsulfonylimidazo[1,5-c]pyrimidin-5-amine	1652813: Inhibition of EED ( 1 to 441 residues) (unknown origin) pre-incubated for 15 mins before biotin-H3K27me3 (19 to 33 residues) addition and further incubated for 30 mins by AlphaScreen.based EED-H3K27me3 peptide competition binding assay	ic50	0.0005	uM
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(1-methylpyrazol-4-yl)-1-methylsulfonylimidazo[1,5-c]pyrimidin-5-amine	1652813: Inhibition of EED ( 1 to 441 residues) (unknown origin) pre-incubated for 15 mins before biotin-H3K27me3 (19 to 33 residues) addition and further incubated for 30 mins by AlphaScreen.based EED-H3K27me3 peptide competition binding assay	ic50	0.0005	uM
N-[(7-amino-5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(2-methyl-3-pyridinyl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	1872356: Binding affinity to EED (unknown origin) assessed as dissociation constant by SPR analysis	kd	0.0005	uM
15-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylimino]-9,12,14,16-tetrazatetracyclo[9.6.1.02,7.014,18]octadeca-1(17),2,4,6,12-pentaen-10-one	1769306: Inhibition of biotinylated H3K27Me3 peptide (19 to 33 residues) binding to His-tagged EED (1 to 441 residues) (unknown origin) preincubated for 15 mins followed by H3K27Me3 addition and measured after 30 mins by alphascreen competition binding assay	ic50	0.0005	uM
(2S,4R)-1-[(2R)-2-[5-[3-[5-[5-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylamino]-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl]-6-methyl-2-pyridinyl]propanoylamino]pentanoylamino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1928070: Binding affinity to PRC2 catalytic core EED (unknown origin) by surface plasmon resonance assay	kd	0.0005	uM
5-[4-[(3S,4R)-4-(dimethylamino)-1-[(2-fluoro-6-methylphenyl)methyl]pyrrolidin-3-yl]piperidin-1-yl]pyrazine-2-carboxamide	1439668: Inhibition of OG(488) labeled probe binding to GST-tagged EED (unknown origin) after 1 hr by LanthaScreen TR-FRET assay	ki	0.0006	uM
N-[(4-ethyl-6-methyl-2-oxo-1H-pyridin-3-yl)methyl]-6-[ethyl(oxan-4-yl)amino]-5-methyl-1-benzofuran-4-carboxamide	1350244: Inhibition of human N-terminal His-tagged EZH2/flag-tagged EED/SUZ12/AEBP2/RBAP48 A677G mutant (2 to end residues) expressed in baculovirus infected Sf9 insect cells using histone H3 (1 to 50 residues)-GGK as substrate after 2 hrs in presence of SAM by fluorescence assay	ic50	0.0006	uM
15-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylimino]-9-(oxan-4-ylmethyl)-5-(trifluoromethyl)-4,9,12,14,16-pentazatetracyclo[9.6.1.02,7.014,18]octadeca-1(17),2,4,6,12-pentaen-10-one	1769306: Inhibition of biotinylated H3K27Me3 peptide (19 to 33 residues) binding to His-tagged EED (1 to 441 residues) (unknown origin) preincubated for 15 mins followed by H3K27Me3 addition and measured after 30 mins by alphascreen competition binding assay	ic50	0.0006	uM
5-fluoro-15-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylimino]-9,12,14,16-tetrazatetracyclo[9.6.1.02,7.014,18]octadeca-1(17),2(7),3,5,12-pentaen-10-one	1769306: Inhibition of biotinylated H3K27Me3 peptide (19 to 33 residues) binding to His-tagged EED (1 to 441 residues) (unknown origin) preincubated for 15 mins followed by H3K27Me3 addition and measured after 30 mins by alphascreen competition binding assay	ic50	0.0006	uM
15-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylimino]-9-methyl-5-(trifluoromethyl)-4,9,12,14,16-pentazatetracyclo[9.6.1.02,7.014,18]octadeca-1(17),2,4,6,12-pentaen-10-one	1769306: Inhibition of biotinylated H3K27Me3 peptide (19 to 33 residues) binding to His-tagged EED (1 to 441 residues) (unknown origin) preincubated for 15 mins followed by H3K27Me3 addition and measured after 30 mins by alphascreen competition binding assay	ic50	0.0006	uM
9-ethyl-15-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylimino]-5-(trifluoromethyl)-4,9,12,14,16-pentazatetracyclo[9.6.1.02,7.014,18]octadeca-1(17),2,4,6,12-pentaen-10-one	1769306: Inhibition of biotinylated H3K27Me3 peptide (19 to 33 residues) binding to His-tagged EED (1 to 441 residues) (unknown origin) preincubated for 15 mins followed by H3K27Me3 addition and measured after 30 mins by alphascreen competition binding assay	ic50	0.0006	uM
(2S,4R)-1-[(2S)-2-[[2-[4-[2-[3-[6-amino-5-[5-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylamino]-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl]-2-pyridinyl]propanoylamino]ethoxy]phenoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1872403: Binding affinity to human N-terminal His-6 tagged EED expressed in Escherichia coli strain BL2(DE3) by SPR analysis	kd	0.0006	uM
N-[(6-methyl-2-oxo-4-propyl-1H-pyridin-3-yl)methyl]-6-[6-(4-methylpiperazin-1-yl)-3-pyridinyl]-1-propan-2-ylindazole-4-carboxamide	711407: Inhibition of PRC2 complex of FLAG-EZH2, EED, SUZ12, AEBP2 and RbAp48 using histone H3 peptide (21 to 44) as substrate and [3H]SAM after 30 mins	ki	0.0006	uM
4-[3-[(3S,4R)-4-(dimethylamino)-1-[(2-fluoro-6-methylphenyl)methyl]pyrrolidin-3-yl]-1-methylindol-7-yl]-1-methylpiperazin-2-one	1439668: Inhibition of OG(488) labeled probe binding to GST-tagged EED (unknown origin) after 1 hr by LanthaScreen TR-FRET assay	ki	0.0007	uM
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-1-methylsulfonyl-8-phenylimidazo[1,5-c]pyrimidin-5-amine	1652813: Inhibition of EED ( 1 to 441 residues) (unknown origin) pre-incubated for 15 mins before biotin-H3K27me3 (19 to 33 residues) addition and further incubated for 30 mins by AlphaScreen.based EED-H3K27me3 peptide competition binding assay	ic50	0.0007	uM
15-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylimino]-5-methyl-6,9,12,14,16-pentazatetracyclo[9.6.1.02,7.014,18]octadeca-1(17),2(7),3,5,12-pentaen-10-one	1769306: Inhibition of biotinylated H3K27Me3 peptide (19 to 33 residues) binding to His-tagged EED (1 to 441 residues) (unknown origin) preincubated for 15 mins followed by H3K27Me3 addition and measured after 30 mins by alphascreen competition binding assay	ic50	0.0007	uM
15-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylimino]-5-(trifluoromethyl)-4,9,12,14,16-pentazatetracyclo[9.6.1.02,7.014,18]octadeca-1(17),2,4,6,12-pentaen-10-one	1769306: Inhibition of biotinylated H3K27Me3 peptide (19 to 33 residues) binding to His-tagged EED (1 to 441 residues) (unknown origin) preincubated for 15 mins followed by H3K27Me3 addition and measured after 30 mins by alphascreen competition binding assay	ic50	0.0007	uM
15-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylimino]-9-(oxan-4-yl)-5-(trifluoromethyl)-4,9,12,14,16-pentazatetracyclo[9.6.1.02,7.014,18]octadeca-1(17),2,4,6,12-pentaen-10-one	1769306: Inhibition of biotinylated H3K27Me3 peptide (19 to 33 residues) binding to His-tagged EED (1 to 441 residues) (unknown origin) preincubated for 15 mins followed by H3K27Me3 addition and measured after 30 mins by alphascreen competition binding assay	ic50	0.0007	uM
15-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylimino]-6,9,12,14,16-pentazatetracyclo[9.6.1.02,7.014,18]octadeca-1(17),2(7),3,5,12-pentaen-10-one	1769306: Inhibition of biotinylated H3K27Me3 peptide (19 to 33 residues) binding to His-tagged EED (1 to 441 residues) (unknown origin) preincubated for 15 mins followed by H3K27Me3 addition and measured after 30 mins by alphascreen competition binding assay	ic50	0.0007	uM
2-cyano-6-[ethyl(oxan-4-yl)amino]-N-[(4-methoxy-6-methyl-2-oxo-1H-pyridin-3-yl)methyl]-5-methyl-1-benzofuran-4-carboxamide	1350244: Inhibition of human N-terminal His-tagged EZH2/flag-tagged EED/SUZ12/AEBP2/RBAP48 A677G mutant (2 to end residues) expressed in baculovirus infected Sf9 insect cells using histone H3 (1 to 50 residues)-GGK as substrate after 2 hrs in presence of SAM by fluorescence assay	ic50	0.0008	uM
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-1-methylsulfonyl-8-(6-methylsulfonyl-3-pyridinyl)imidazo[1,5-c]pyrimidin-5-amine	1652813: Inhibition of EED ( 1 to 441 residues) (unknown origin) pre-incubated for 15 mins before biotin-H3K27me3 (19 to 33 residues) addition and further incubated for 30 mins by AlphaScreen.based EED-H3K27me3 peptide competition binding assay	ic50	0.0008	uM
9-cyclobutyl-15-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylimino]-5-(trifluoromethyl)-4,9,12,14,16-pentazatetracyclo[9.6.1.02,7.014,18]octadeca-1(17),2,4,6,12-pentaen-10-one	1769306: Inhibition of biotinylated H3K27Me3 peptide (19 to 33 residues) binding to His-tagged EED (1 to 441 residues) (unknown origin) preincubated for 15 mins followed by H3K27Me3 addition and measured after 30 mins by alphascreen competition binding assay	ic50	0.0008	uM
6-fluoro-15-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylimino]-9,12,14,16-tetrazatetracyclo[9.6.1.02,7.014,18]octadeca-1(17),2(7),3,5,12-pentaen-10-one	1769306: Inhibition of biotinylated H3K27Me3 peptide (19 to 33 residues) binding to His-tagged EED (1 to 441 residues) (unknown origin) preincubated for 15 mins followed by H3K27Me3 addition and measured after 30 mins by alphascreen competition binding assay	ic50	0.0008	uM
9-(3,3-difluorocyclobutyl)-15-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylimino]-5-(trifluoromethyl)-4,9,12,14,16-pentazatetracyclo[9.6.1.02,7.014,18]octadeca-1(17),2,4,6,12-pentaen-10-one	1769306: Inhibition of biotinylated H3K27Me3 peptide (19 to 33 residues) binding to His-tagged EED (1 to 441 residues) (unknown origin) preincubated for 15 mins followed by H3K27Me3 addition and measured after 30 mins by alphascreen competition binding assay	ic50	0.0008	uM
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-8-(2-methyl-4-methylsulfonylphenyl)-1-methylsulfonylimidazo[1,5-c]pyrimidin-5-amine	1652813: Inhibition of EED ( 1 to 441 residues) (unknown origin) pre-incubated for 15 mins before biotin-H3K27me3 (19 to 33 residues) addition and further incubated for 30 mins by AlphaScreen.based EED-H3K27me3 peptide competition binding assay	ic50	0.0009	uM
(3R,4S)-1-[(1S)-7-fluoro-2,3-dihydro-1H-inden-1-yl]-N,N-dimethyl-4-(1-methylindol-3-yl)pyrrolidin-3-amine	1452116: Binding affinity to GST tagged EED (unknown origin) after 1 hr by OG(488) probe based TR-FRET assay	ki	0.0010	uM
[3-[(3S,4R)-4-(dimethylamino)-1-[(2-fluoro-6-methylphenyl)methyl]pyrrolidin-3-yl]-1-methylindol-7-yl]-(3-fluoroazetidin-1-yl)methanone	1439668: Inhibition of OG(488) labeled probe binding to GST-tagged EED (unknown origin) after 1 hr by LanthaScreen TR-FRET assay	ki	0.0010	uM
(2S,4R)-1-[(2S)-2-[[2-[4-[2-[3-[5-[5-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylamino]-[1,2,4]triazolo[4,3-c]pyrimidin-8-yl]-6-methyl-2-pyridinyl]propanoylamino]ethoxy]phenoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1729439: Binding affinity to human N-terminal His6-tagged/thrombin cleavage site fused/ AVI-tagged EED (1 to 441 residues) expressed in Escherichia coli BL21(DE3) cells by surface plasmon resonance method	kd	0.0010	uM

CTD chemical–gene interactions

32 total (human), top 30 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, increases expression, decreases expression	3
Resveratrol	affects cotreatment, increases expression	2
Cyclosporine	affects expression, decreases expression	2
TAK-243	increases sumoylation	1
methylmercuric chloride	increases expression	1
bisphenol A	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
azoxystrobin	increases expression	1
K 7174	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
dorsomorphin	affects cotreatment, increases expression	1
enzalutamide	affects binding, affects cotreatment, decreases reaction, decreases expression, increases reaction	1
GSK-2816126	increases reaction, affects binding, affects cotreatment, decreases reaction, decreases expression	1
Leflunomide	decreases expression	1
Acetaminophen	increases expression	1
Amiodarone	increases expression	1
Benzene	increases expression	1
Benzo(a)pyrene	increases expression	1
Copper	affects binding, decreases expression	1
Coumestrol	affects cotreatment, increases expression	1
Dichlorodiphenyl Dichloroethylene	increases expression	1
Disulfiram	affects binding, decreases expression	1
Formaldehyde	increases expression	1
Ivermectin	decreases expression	1
Methotrexate	affects response to substance	1
Methyl Methanesulfonate	increases expression	1
Plant Extracts	increases expression, affects cotreatment	1
7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide	decreases expression	1
Oxyquinoline	decreases expression	1
Aflatoxin B1	decreases methylation	1

ChEMBL screening assays

176 unique, capped per target: 170 binding, 6 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3382328	Binding	Displacement of FITC-labeled EZH2 peptide from recombinant N-terminal 6His-tagged EED (residues 81 to 441) (unknown origin) expressed in Escherichia coli strain BL21 (DE3) after 1 hr by fluorescence polarization assay	Astemizole arrests the proliferation of cancer cells by disrupting the EZH2-EED interaction of polycomb repressive complex 2. — J Med Chem
CHEMBL4613065	Functional	Inhibition of EED in SCID mouse xenografted with human KARPAS422 cells assessed as reduction in H3K27me3 level in tumor at 100 mg/kg, po dosed as single administration measured after 24 hrs by Western blotting analysis	EEDi-5285: An Exceptionally Potent, Efficacious, and Orally Active Small-Molecule Inhibitor of Embryonic Ectoderm Development. — J Med Chem

Cellosaurus cell lines

6 cell lines: 3 embryonic stem cell, 2 cancer cell line, 1 induced pluripotent stem cell

First 10 cell lines (id-ordered, not curated):

Cellosaurus	Name	Category	Sex
CVCL_A1E5	SEES3-1V human EED, clone1	Embryonic stem cell	Male
CVCL_A1E6	SEES3-1V human EED, clone2	Embryonic stem cell	Male
CVCL_A1E7	SEES3-1V human EED, clone3	Embryonic stem cell	Male
CVCL_SL42	HAP1 EED (-) 1	Cancer cell line	Male
CVCL_SL43	HAP1 EED (-) 2	Cancer cell line	Male
CVCL_YC77	UMILi014-A	Induced pluripotent stem cell	Male

Clinical trials (associated diseases)

300 trials via MONDO — disease-level, not drug-specific.

Trial	Phase	Status	Title
NCT00391261	PHASE4	COMPLETED	An Open-label Trial of Metformin for Weight Control of Pediatric Patients on Antipsychotic Medications.
NCT01028820	PHASE4	COMPLETED	FMRI Brain Activation of Aripiprazole Treatment in Autism Spectrum Disorders
NCT01333865	PHASE4	COMPLETED	A Study of Memantine Hydrochloride (Namenda®) for Cognitive and Behavioral Impairment in Adults With Autism Spectrum Disorders
NCT01337700	PHASE4	COMPLETED	Milnacipran in Autism and the Functional Locus Coeruleus and Noradrenergic Model of Autism
NCT01695200	PHASE4	COMPLETED	Omega-3 Fatty Acids in Autism Spectrum Disorders
NCT02096952	PHASE4	COMPLETED	Methylphenidate ER Liquid Formulation in Adults With ASD and ADHD
NCT02235467	PHASE4	COMPLETED	Multisite Study: Parental Training Using Video Modelling to Develop Social Skills in Children With Autism
NCT02940574	PHASE4	COMPLETED	Neural and Behavioral Effects of Oxytocin in Autism Spectrum Disorders
NCT03333629	PHASE4	COMPLETED	Promoting Positive Outcomes for Individuals With ASD: Linking Early Detection, Treatment, and Long-term Outcomes
NCT03337646	PHASE4	COMPLETED	Evaluation of the Effect and Safety of Lisdexamfetamine in Children Aged 6-12 With ADHD and Autism
NCT03538431	PHASE4	COMPLETED	Improving Driving in Young People With Autism Spectrum Disorders
NCT03757585	PHASE4	COMPLETED	Natural Treatments for the Management of Emotional Dysregulation in Youth With Non-verbal Learning Disability (NVLD) and/or Autism Spectrum Disorders (ASD)
NCT04903353	PHASE4	COMPLETED	Pragmatic Trial Comparing Weight Gain in Children With Autism Taking Risperidone Versus Aripiprazole
NCT05063656	PHASE4	COMPLETED	Biomarker-Driven Pharmacological Treatment of Adolescents With Autism Spectrum Disorder With Gabapentin
NCT05146245	PHASE4	UNKNOWN	Safety and Pharmacokinetics of Antipsychotics in Children 2: Studying TDM in an RCT
NCT05916339	PHASE4	RECRUITING	AWARE: Management of ADHD in Autism Spectrum Disorder
NCT05954052	PHASE4	TERMINATED	A Study of Glutathione in Children With Autism Spectrum Disorder
NCT06853665	PHASE4	RECRUITING	The TEAM Study - Treatment Efficacy for Autism/Attention Using Mixed Amphetamine
NCT07054697	PHASE4	COMPLETED	Pilot-RCT With Individualized Homeopathic Treatment in the Children With Autism Spectrum Disorder
NCT07161804	PHASE4	COMPLETED	Pilot RCT Using Homeopathic Medicines in ASD
NCT07439042	PHASE4	NOT_YET_RECRUITING	Buspirone for Anxiety in Autistic Youth
NCT01302964	PHASE3	COMPLETED	Mirtazapine Treatment of Anxiety in Children and Adolescents With Pervasive Developmental Disorders
NCT01706523	PHASE3	TERMINATED	Open Label Extension Study of STX209 (Arbaclofen) in Autism Spectrum Disorders
NCT01825798	PHASE3	COMPLETED	Treatment of Overweight Induced by Antipsychotic Medication in Young People With Autism Spectrum Disorders (ASD)
NCT01972074	PHASE3	COMPLETED	Behavioral and Neural Response to Memantine in Adolescents With Autism Spectrum Disorder
NCT02985749	PHASE3	COMPLETED	A Study of Oxytocin for the Treatment of Social Impairment in Individuals With High Functioning Autism Spectrum Disorder
NCT03197922	PHASE3	COMPLETED	Treatment of Encopresis in Children With Autism Spectrum Disorders
NCT03504917	PHASE3	TERMINATED	A Study of Balovaptan in Adults With Autism Spectrum Disorder With a 2-Year Open-Label Extension
NCT03553875	PHASE3	TERMINATED	Memantine for the Treatment of Social Deficits in Youth With Disorders of Impaired Social Interactions
NCT03640156	PHASE3	COMPLETED	Modulating Socially Adaptive Mirror System Functioning in Autism by Oxytocin
NCT03715153	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children Aged From 2 to Less Than 7 Years Old With Autism Spectrum Disorder.
NCT03715166	PHASE3	TERMINATED	Efficacy and Safety of Bumetanide Oral Liquid Formulation in Children and Adolescents Aged From 7 to Less Than 18 Years Old With Autism Spectrum Disorder
NCT04233502	PHASE3	WITHDRAWN	Efficacy and Safety of Slenyto for Insomnia in Children With ASD
NCT04578756	PHASE3	COMPLETED	Open-Label, Flexible-dose Study to Evaluate the Long-Term Safety and Tolerability of Cariprazine in the Treatment of Pediatric Participants With Schizophrenia, Bipolar I Disorder, or Autism Spectrum Disorder
NCT04623398	PHASE3	COMPLETED	Effect of Lithium in Patients With Autism Spectrum Disorder and Phelan-McDermid Syndrome (SHANK3 Haploinsufficiency)
NCT04725383	PHASE3	TERMINATED	Amitriptyline for Repetitive Behaviors in Autism Spectrum Disorders
NCT05212493	PHASE3	COMPLETED	The Effects of Medical Cannabis in Children With Autistic Spectrum Disorder
NCT05361707	PHASE3	UNKNOWN	Evaluating the Effects of Tasimelteon in Individuals With Autism Spectrum Disorder (ASD) and Sleep Disturbances
NCT05439616	PHASE3	COMPLETED	Study of Cariprazine Oral Capsules or Solution to Assess Adverse Events and Change in Irritability Due to Autism Spectrum Disorder (ASD) in Participants Aged 5-17 Years With ASD
NCT06229210	PHASE3	RECRUITING	Safety and Tolerability Trial of Lumateperone in Pediatric Patients With Schizophrenia, Bipolar Disorder or Autism Spectrum Disorder