RBBP4

Summary

RBBP4 (RB binding protein 4, chromatin remodeling factor, HGNC:9887) is a protein-coding gene on chromosome 1p35.1, encoding Histone-binding protein RBBP4 (Q09028). Core histone-binding subunit that may target chromatin assembly factors, chromatin remodeling factors and histone deacetylases to their histone substrates in a manner that is regulated by nucleosomal DNA. It is a common-essential gene (DepMap: required in 98.7% of cancer cell lines).

This gene encodes a ubiquitously expressed nuclear protein which belongs to a highly conserved subfamily of WD-repeat proteins. It is present in protein complexes involved in histone acetylation and chromatin assembly. It is part of the Mi-2 complex which has been implicated in chromatin remodeling and transcriptional repression associated with histone deacetylation. This encoded protein is also part of co-repressor complexes, which is an integral component of transcriptional silencing. It is found among several cellular proteins that bind directly to retinoblastoma protein to regulate cell proliferation. This protein also seems to be involved in transcriptional repression of E2F-responsive genes. Three transcript variants encoding different isoforms have been found for this gene.

Source: NCBI Gene 5928 — RefSeq curated summary.

At a glance

• Clinical variants (ClinVar): 57 total
• Druggable target: yes — 1 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 98.7% of screened cell lines (common-essential)
• MANE Select transcript: NM_005610

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:9887
Approved symbol	RBBP4
Name	RB binding protein 4, chromatin remodeling factor
Location	1p35.1
Locus type	gene with protein product
Status	Approved
Aliases	RbAp48, NURF55, lin-53
Ensembl gene	ENSG00000162521
Ensembl biotype	protein_coding
OMIM	602923
Entrez	5928

Gene structure

Transcript identifiers

Ensembl transcripts: 19 — 9 protein_coding, 5 nonsense_mediated_decay, 4 retained_intron, 1 protein_coding_CDS_not_defined

ENST00000373485, ENST00000373493, ENST00000401893, ENST00000414241, ENST00000445722, ENST00000458695, ENST00000460669, ENST00000463378, ENST00000465780, ENST00000475321, ENST00000477563, ENST00000482190, ENST00000490500, ENST00000492348, ENST00000524393, ENST00000525506, ENST00000526193, ENST00000527118, ENST00000531983

RefSeq mRNA: 3 — MANE Select: NM_005610 NM_001135255, NM_001135256, NM_005610

CCDS: CCDS366, CCDS44105, CCDS44106

Canonical transcript exons

ENST00000373493 — 12 exons

Exon	Start	End
ENSE00001460695	32651208	32651322
ENSE00001864556	32679640	32686211
ENSE00003513050	32668739	32668854
ENSE00003515597	32651914	32652061
ENSE00003523120	32668972	32669132
ENSE00003586592	32672642	32672699
ENSE00003612598	32669486	32669563
ENSE00003619860	32668225	32668398
ENSE00003622847	32669231	32669357
ENSE00003649792	32672450	32672526
ENSE00003784257	32672791	32672901
ENSE00003786733	32657427	32657572

Expression profiles

Bgee: expression breadth ubiquitous, 258 present calls, max score 99.24.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 99.6868 / max 855.6028, expressed in 1823 samples.

FANTOM5 promoters (3 alternative TSS)

Promoter ID	TPM avg	Samples expressed
1997	98.8756	1823
1996	0.7601	469
201456	0.0511	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ganglionic eminence	UBERON:0004023	99.24	gold quality
ventricular zone	UBERON:0003053	99.23	gold quality
cortical plate	UBERON:0005343	98.65	gold quality
bone marrow cell	CL:0002092	98.37	gold quality
right testis	UBERON:0004534	97.85	gold quality
left testis	UBERON:0004533	97.55	gold quality
adrenal tissue	UBERON:0018303	97.33	gold quality
monocyte	CL:0000576	97.28	gold quality
colonic epithelium	UBERON:0000397	97.26	gold quality
vermiform appendix	UBERON:0001154	97.23	gold quality
leukocyte	CL:0000738	97.21	gold quality
islet of Langerhans	UBERON:0000006	97.09	gold quality
stromal cell of endometrium	CL:0002255	97.01	gold quality
rectum	UBERON:0001052	96.95	gold quality
smooth muscle tissue	UBERON:0001135	96.78	gold quality
gall bladder	UBERON:0002110	96.46	gold quality
right ovary	UBERON:0002118	96.34	gold quality
body of pancreas	UBERON:0001150	96.28	gold quality
calcaneal tendon	UBERON:0003701	96.26	gold quality
lymph node	UBERON:0000029	96.25	gold quality
testis	UBERON:0000473	96.15	gold quality
endocervix	UBERON:0000458	96.13	gold quality
right adrenal gland	UBERON:0001233	96.10	gold quality
right adrenal gland cortex	UBERON:0035827	96.02	gold quality
left ovary	UBERON:0002119	95.94	gold quality
left adrenal gland	UBERON:0001234	95.90	gold quality
left uterine tube	UBERON:0001303	95.85	gold quality
ectocervix	UBERON:0012249	95.85	gold quality
body of uterus	UBERON:0009853	95.80	gold quality
pancreas	UBERON:0001264	95.76	gold quality

Single-cell (SCXA)

Detected in 4 experiment(s), a significant marker in 4.

Experiment	Marker?	Max mean expression
E-CURD-112	yes	40.82
E-CURD-122	yes	16.14
E-CURD-88	yes	3.89
E-ANND-3	no	0.00

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): E2F6, MYC, NFKB, PARP1

miRNA regulators (miRDB)

200 targeting RBBP4, 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-3613-3P	100.00	76.36	7965
HSA-MIR-450A-1-3P	100.00	69.33	1837
HSA-MIR-1277-5P	100.00	73.95	5056
HSA-MIR-3064-3P	100.00	70.09	1254
HSA-MIR-5193	100.00	67.26	1744
HSA-MIR-518D-5P	100.00	67.51	979
HSA-MIR-518E-5P	100.00	67.66	954
HSA-MIR-518F-5P	100.00	67.51	979
HSA-MIR-519A-5P	100.00	67.66	954
HSA-MIR-519B-5P	100.00	67.66	954
HSA-MIR-519C-5P	100.00	67.66	954
HSA-MIR-520C-5P	100.00	67.51	979
HSA-MIR-522-5P	100.00	67.66	954
HSA-MIR-523-5P	100.00	67.66	954
HSA-MIR-526A-5P	100.00	67.51	979
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-196A-5P	100.00	68.16	684
HSA-MIR-196B-5P	100.00	68.16	681
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-4692	100.00	67.32	2066
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-186-5P	99.99	70.83	3707
HSA-MIR-520G-5P	99.99	66.76	658
HSA-MIR-4775	99.98	75.00	6394
HSA-MIR-373-5P	99.98	75.36	4753

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 98.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 38)

• Upergulation of CAF-1 p48 subunit by overexpression of tuberous sclerosis gene products. (PMID:12893285)
• expression of three (Beclin 1, RbAp48 and Pir51) were increased and one (aldolase b) was decreased in liver tumor tissues. (PMID:14966907)
• RbAp48 is a NF-kappaB-regulated gene playing an important role in thyroid cancer cell autonomous proliferation. (PMID:17244783)
• RbAp48-mediated transformation of HPV16 is probably because of the regulation by RbAp48 of tumor suppressors retinoblastoma and p53, apoptosis-related enzymes caspase-3 and caspase-8, E6, E7, cyclin D1 (CCND1), and c-MYC. (PMID:17616526)
• In conclusion, the data support a model whereby RbAp48 regulates cellular morphology and cytoskeletal organization by increasing K-Ras activity and signaling through MAPK. (PMID:17974974)
• Data show that RbAp46 and RbAp48 interact with estrogen receptor (ER)alpha at endogenous, estrogen-responsive genes and alter expression of endogenous, ERalpha-activated and -repressed genes in MCF-7 breast cancer cells. (PMID:18577416)
• Results report that transgenic expression of RbAp48 resulted in the development of autoimmune exocrinopathy resembling Sjogren’s syndrome. (PMID:19015307)
• The FOG-1 peptide contacts a negatively charged binding pocket on top of the RbAp48 beta-propeller that is distinct from the binding surface used by RpAp48 to contact histone H4 (PMID:21047798)
• Data identified RBBP4 and RBBP9 as required for maintenance of multiple PS cell types, and both RBBPs were bound to RB in PS cells. (PMID:21689726)
• study of the interaction of the histone H3-H4 complex with the RbAp48 and their exchange with a second histone chaperone, anti-silencing function protein 1 (ASF1); exchange of histones H3-H4 between these two histone chaperones has a central role in the assembly of new nucleosomes (PMID:23178455)
• The most significant change was an age-related decline in RbAp48, a histone-binding protein that modifies histone acetylation. (PMID:23986399)
• RbAp48 recognizes MTA1 using the same site that it uses to bind histone H4, showing that assembly into NuRD modulates RbAp46/48 interactions with histones. (PMID:24920672)
• It is associated with episodic memory performance. (PMID:25150575)
• Our results reveal that the protein structure does not affect ligand binding, and the top three TCM candidates Bittersweet alkaloid II, Eicosandioic acid, and Perivine might resolve the instability of the RbAp48-FOG1 complex (PMID:25165715)
• Our RBBP4-PHF6 complex structure provides insights into the molecular basis of PHF6-NuRD complex interaction and implicates a role for PHF6 in chromatin structure modulation and gene regulation. (PMID:25601084)
• RbAp48 was identified as critical in the proliferation of hypopharyngeal carcinoma in both in vitro and in vivo experiments. (PMID:26376479)
• RBBP4 functions as a novel regulatory factor to increase the efficiency of importin alpha/beta-mediated nuclear import (PMID:26491019)
• RBBP4 interacts with ep300 protein to form a complex that drives the expression of methylguanine-DNA-methyltransferase , RAD51, and other selected DNA repair genes through histone acetylation. (PMID:26972001)
• The crystal structure reveals an extensive interface between MTA1 and RBBP4. (PMID:27098840)
• The MTA1 subunit of the nucleosome remodeling and deacetylase complex can recruit two copies of RBBP4/RBBP7. (PMID:27144666)
• RbAp48 is likely to act as a potent antiretroviral defense. (PMID:27222146)
• The binding interface between AEBP and RBBP4 is relatively small compared with PHF6, histone H3 and FOG-1, indicating that AEBP may not have been the only region that participates in RBBP4 recognition. (PMID:29134516)
• BCL11A interacts with histone methyltransferase (PRC2) and histone deacetylase (NuRD and SIN3A) complexes through their common subunit, RBBP4/7. (PMID:29263092)
• RBAP48 overexpression contributes to the radiosensitivity of AGS gastric cancer cells via phosphoinositide3-kinase/protein kinase B pathway suppression. (PMID:29901205)
• ARMC12 promotes neuroblastoma progression through interaction with RBBP4. (PMID:30026490)
• RBBP4 forms a negatively charged channel that binds to ZNF827 through a network of electrostatic interactions. (PMID:30045876)
• The authors suggest that RBBP4 is linked to HIV-1 transcriptional silencing and that it may be a new type of viral transcription inhibitor. (PMID:31435636)
• In summary, this is the first study showing the expression of RBBP4 in colon cancer and revealing that RBBP4 up-regulation is significantly associated with poor prognosis in colon cancer pa- tients. (PMID:31501018)
• RBBP4 promotes colon cancer malignant progression via regulating Wnt/beta-catenin pathway. (PMID:32994691)
• The topology of chromatin-binding domains in the NuRD deacetylase complex. (PMID:33264408)
• Overlapping functions of RBBP4 and RBBP7 in regulating cell proliferation and histone H3.3 deposition during mouse preimplantation development. (PMID:34709113)
• RBBP4-p300 axis modulates expression of genes essential for cell survival and is a potential target for therapy in glioblastoma. (PMID:35231103)
• RBBP4 plays a vital role in the malignant progression of triple-negative breast cancer by regulating epithelial-mesenchymal transition. (PMID:35622231)
• Circ_0110498 facilitates the cisplatin resistance of non-small cell lung cancer by mediating the miR-1287-5p/RBBP4 axis. (PMID:36691322)
• RBBP4 regulates the expression of the Mre11-Rad50-NBS1 (MRN) complex and promotes DNA double-strand break repair to mediate glioblastoma chemoradiotherapy resistance. (PMID:36736531)
• CircAGO2 promotes colorectal cancer progression by inhibiting heat shock protein family B (small) member 8 via miR-1-3p/retinoblastoma binding protein 4 axis. (PMID:36881338)
• Interpreting the molecular mechanisms of RBBP4/7 and their roles in human diseases (Review). (PMID:38577935)
• RBBP4: A novel diagnostic and prognostic biomarker for non-small-cell lung cancer correlated with autophagic cell death. (PMID:39109577)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	rbbp4	ENSDARG00000029058
mus_musculus	Rbbp4	ENSMUSG00000057236
rattus_norvegicus	Rbbp4l1	ENSRNOG00000028052

Paralogs (9): ERCC8 (ENSG00000049167), GEMIN5 (ENSG00000082516), RBBP7 (ENSG00000102054), WDR59 (ENSG00000103091), GRWD1 (ENSG00000105447), PEX7 (ENSG00000112357), WDR77 (ENSG00000116455), WDR24 (ENSG00000127580), WDR73 (ENSG00000177082)

Protein

Protein identifiers

Histone-binding protein RBBP4 — Q09028 (reviewed: Q09028)

Alternative names: Chromatin assembly factor 1 subunit C, Chromatin assembly factor I p48 subunit, Nucleosome-remodeling factor subunit RBAP48, Retinoblastoma-binding protein 4, Retinoblastoma-binding protein p48

All UniProt accessions (10): C9JPP3, E9PIC4, E9PND5, E9PNS2, E9PNS6, Q09028, H0YCT5, H0YDK2, H0YEU5, H0YF10

UniProt curated annotations — full annotation on UniProt →

Function. Core histone-binding subunit that may target chromatin assembly factors, chromatin remodeling factors and histone deacetylases to their histone substrates in a manner that is regulated by nucleosomal DNA. Component of the chromatin assembly factor 1 (CAF-1) complex, which is required for chromatin assembly following DNA replication and DNA repair. Component of the core histone deacetylase (HDAC) complex, which promotes histone deacetylation and consequent transcriptional repression. Component of the nucleosome remodeling and histone deacetylase complex (the NuRD complex), which promotes transcriptional repression by histone deacetylation and nucleosome remodeling. Component of the PRC2 complex, which promotes repression of homeotic genes during development. Component of the NURF (nucleosome remodeling factor) complex.

Subunit / interactions. Binds directly to helix 1 of the histone fold of histone H4, a region that is not accessible when H4 is in chromatin. Subunit of the chromatin assembly factor 1 (CAF-1) complex, which is composed of RBBP4, CHAF1B and CHAF1A. Subunit of the core histone deacetylase (HDAC) complex, which is composed of HDAC1, HDAC2, RBBP4 and RBBP7. The core HDAC complex associates with SIN3A, ARID4B/SAP180, SAP18, SAP30, SAP130, SUDS3/SAP45 and possibly ARID4A/RBP1 and ING1 to form the SIN3 HDAC complex. Component of the nucleosome remodeling and deacetylase (NuRD) repressor complex, composed of core proteins MTA1, MTA2, MTA3, RBBP4, RBBP7, HDAC1, HDAC2, MBD2, MBD3, and peripherally associated proteins CDK2AP1, CDK2AP2, GATAD2A, GATAD2B, CHD3, CHD4 and CHD5. The exact stoichiometry of the NuRD complex is unknown, and some subunits such as MBD2 and MBD3, GATAD2A and GATAD2B, and CHD3, CHD4 and CHD5 define mutually exclusive NuRD complexes. Interacts with ZNF512B; the interaction is direct and may play a role in repressing gene expression. The NuRD complex may also interact with MBD3L1 and MBD3L2. Component of the PRC2 complex, which consists of the core subunits EED, EZH1 or EZH2, SUZ12, and RBBP4, and various combinations of accessory subunits including AEBP2, JARID2, PHF19, MTF2 and EPOP. Forms a monomeric PRC2.2 (class 2) complex consisting of at least SUZ12, RBBP4, AEBP2 and JARID2. Forms a dimeric PRC2.1 (class 1, PRC-PCL) complex consisting of at least SUZ12, RBBP4, and PHF19; PHF19 stabilizes the dimeric structure which enhances PRC2 interaction with chromatin. Component of the NURF-1 ISWI chromatin remodeling complex (also called the nucleosome-remodeling factor (NURF) complex) at least composed of SMARCA1 (isoform 2), BPTF, RBBP4 and RBBP7. Within the complex interacts with isoform 2 of SMARCA1. Component of the BPFT-SMARCA1 complex at least composed of SMARCA1 (isoform 1), BPFT, RBBP4 and RBBP7; the complex is catalytically inactive and does not remodel chromatin. Within the complex interacts with isoform 1 of SMARCA1. Interacts with the ISWI chromatin remodeling complex component SMARCA5; the interaction is direct. Interacts with the viral protein-binding domain of the retinoblastoma protein (RB1). Component of the DREAM complex (also named LINC complex) at least composed of E2F4, E2F5, LIN9, LIN37, LIN52, LIN54, MYBL1, MYBL2, RBL1, RBL2, RBBP4, TFDP1 and TFDP2. The complex exists in quiescent cells where it represses cell cycle-dependent genes. It dissociates in S phase when LIN9, LIN37, LIN52 and LIN54 form a subcomplex that binds to MYBL2. Found in a complex composed of at least SINHCAF, SIN3A, HDAC1, SAP30, RBBP4, OGT and TET1. Interacts with ZNF827; the interaction is direct and recruits RBBP4 to telomeres. Interacts with MTA1; the interaction is direct and mutually exclusive with binding histone H4. Interacts with ARMC12 (via ARM domains). Interacts with BRCA1. Interacts with CDK2AP1. Interacts with CREBBP, and this interaction may be enhanced by the binding of phosphorylated CREB1 to CREBBP. Interacts with ERCC6. Interacts with HDAC7. Interacts with PHF6. Interacts with PWWP2B. Interacts with SPEN/MINT. Interacts with SUV39H1. Interacts with MECOM and PRDM16.

Subcellular location. Nucleus. Chromosome. Telomere.

Tissue specificity. Expressed in neuroblastoma cells.

Similarity. Belongs to the WD repeat RBAP46/RBAP48/MSI1 family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q09028-1	1	yes
Q09028-2	2
Q09028-3	3
Q09028-4	4

RefSeq proteins (3): NP_001128727, NP_001128728, NP_005601* (*=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
IPR020472	WD40_PAC1	Repeat
IPR022052	Histone-bd_RBBP4-like_N	Domain
IPR036322	WD40_repeat_dom_sf	Homologous_superfamily
IPR050459	WD_repeat_RBAP46/RBAP48/MSI1	Family

Pfam: PF00400, PF12265

UniProt features (88 total): strand 43, mutagenesis site 11, helix 8, repeat 7, modified residue 5, turn 4, cross-link 3, splice variant 3, initiator methionine 1, chain 1, sequence conflict 1, region of interest 1

Structure

Experimental structures (PDB)

50 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
4R7A	X-RAY DIFFRACTION	1.85
7M40	X-RAY DIFFRACTION	1.88
2XU7	X-RAY DIFFRACTION	1.9
5XXQ	X-RAY DIFFRACTION	1.9
6BW4	X-RAY DIFFRACTION	2
9V5M	X-RAY DIFFRACTION	2.1
5Y1U	X-RAY DIFFRACTION	2.14
4PBZ	X-RAY DIFFRACTION	2.15
6BW3	X-RAY DIFFRACTION	2.2
8TX8	X-RAY DIFFRACTION	2.2
3GFC	X-RAY DIFFRACTION	2.3
5VTB	X-RAY DIFFRACTION	2.4
4PBY	X-RAY DIFFRACTION	2.5
4PC0	X-RAY DIFFRACTION	2.5
6ZRD	X-RAY DIFFRACTION	2.5
7N40	X-RAY DIFFRACTION	2.55
6ZRC	X-RAY DIFFRACTION	2.6
5XWR	X-RAY DIFFRACTION	2.69
9XZI	X-RAY DIFFRACTION	2.69
6G16	X-RAY DIFFRACTION	2.8
6NQ3	X-RAY DIFFRACTION	2.89
5WAI	X-RAY DIFFRACTION	2.9
8VMI	ELECTRON MICROSCOPY	3.1
8VNV	ELECTRON MICROSCOPY	3.1
9C8U	ELECTRON MICROSCOPY	3.1
5FXY	X-RAY DIFFRACTION	3.2
5WAK	X-RAY DIFFRACTION	3.2
8FYH	ELECTRON MICROSCOPY	3.4
9DCH	ELECTRON MICROSCOPY	3.4
7Y5L	X-RAY DIFFRACTION	3.42

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q09028-F1	92.20	0.87

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 (8): 2, 4, 110, 160, 355, 4, 4, 160

Mutagenesis-validated functional residues (11):

Position	Phenotype
35	loss of interaction with armc12.
43	loss of interaction with znf827 and loss of localization to telomeres; when associated with a-73.
73	loss of interaction with znf827 and loss of localization to telomeres; when associated with a-43.
126–128	loss of interaction with znf827.
126	loss of interaction with znf827 and loss of localization to telomeres; when associated with a-128 and a-179.
128	loss of interaction with znf827 and loss of localization to telomeres; when associated with a-126 and a-179.
179	loss of interaction with znf827 and loss of localization to telomeres; when associated with a-126 and a-128.
181	loss of interaction with znf827 and loss of localization to telomeres.
231	decreased interaction with znf827; when associated with a-277.
277	decreased interaction with znf827; when associated with a-231.
395	decreased interaction with znf827.

Function

Pathways and Gene Ontology

Reactome pathways

29 pathways

ID	Pathway
R-HSA-1362277	Transcription of E2F targets under negative control by DREAM complex
R-HSA-1362300	Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1
R-HSA-1538133	G0 and Early G1
R-HSA-156711	Polo-like kinase mediated events
R-HSA-212300	PRC2 methylates histones and DNA
R-HSA-2559580	Oxidative Stress Induced Senescence
R-HSA-3214815	HDACs deacetylate histones
R-HSA-3214841	PKMTs methylate histone lysines
R-HSA-427389	ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression
R-HSA-5617472	Activation of anterior HOX genes in hindbrain development during early embryogenesis
R-HSA-606279	Deposition of new CENPA-containing nucleosomes at the centromere
R-HSA-6804758	Regulation of TP53 Activity through Acetylation
R-HSA-69202	Cyclin E associated events during G1/S transition
R-HSA-69205	G1/S-Specific Transcription
R-HSA-69656	Cyclin A:Cdk2-associated events at S phase entry
R-HSA-73762	RNA Polymerase I Transcription Initiation
R-HSA-8943724	Regulation of PTEN gene transcription
R-HSA-8953750	Transcriptional Regulation by E2F6
R-HSA-9609690	HCMV Early Events
R-HSA-9679191	Potential therapeutics for SARS
R-HSA-9710421	Defective pyroptosis
R-HSA-9764725	Negative Regulation of CDH1 Gene Transcription
R-HSA-9843940	Regulation of endogenous retroelements by KRAB-ZFP proteins
R-HSA-9844594	Transcriptional regulation of brown and beige adipocyte differentiation by EBF2
R-HSA-9845323	Regulation of endogenous retroelements by Piwi-interacting RNAs (piRNAs)
R-HSA-9909649	Regulation of PD-L1(CD274) transcription
R-HSA-9937850	NuRD complex assembly
R-HSA-9940951	Interaction of NuRD complexes with transcription factors
R-HSA-9976102	Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)

MSigDB gene sets: 432 (showing top): GGGACCA_MIR133A_MIR133B, PID_HDAC_CLASSI_PATHWAY, E2F_Q4_01, BORCZUK_MALIGNANT_MESOTHELIOMA_UP, GOBP_REGULATION_OF_CELLULAR_RESPONSE_TO_GROWTH_FACTOR_STIMULUS, REACTOME_G1_S_SPECIFIC_TRANSCRIPTION, PID_TELOMERASE_PATHWAY, RODRIGUES_THYROID_CARCINOMA_POORLY_DIFFERENTIATED_UP, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, REACTOME_RNA_POLYMERASE_I_TRANSCRIPTION_INITIATION, MORF_HDAC1, MCBRYAN_PUBERTAL_TGFB1_TARGETS_DN, KAUFFMANN_DNA_REPAIR_GENES, PUJANA_CHEK2_PCC_NETWORK, REACTOME_ADHERENS_JUNCTIONS_INTERACTIONS

GO Biological Process (19): negative regulation of transcription by RNA polymerase II (GO:0000122), DNA replication (GO:0006260), DNA repair (GO:0006281), nucleosome assembly (GO:0006334), DNA replication-dependent chromatin assembly (GO:0006335), chromatin remodeling (GO:0006338), regulation of DNA-templated transcription (GO:0006355), brain development (GO:0007420), negative regulation of cell population proliferation (GO:0008285), negative regulation of cell migration (GO:0030336), negative regulation of transforming growth factor beta receptor signaling pathway (GO:0030512), regulation of cell fate specification (GO:0042659), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of DNA-templated transcription (GO:0045893), negative regulation of stem cell population maintenance (GO:1902455), positive regulation of stem cell population maintenance (GO:1902459), regulation of stem cell differentiation (GO:2000736), chromatin organization (GO:0006325), DNA damage response (GO:0006974)

GO Molecular Function (6): RNA polymerase II cis-regulatory region sequence-specific DNA binding (GO:0000978), histone binding (GO:0042393), histone deacetylase binding (GO:0042826), protein binding (GO:0005515), ATP-dependent activity, acting on DNA (GO:0008094), nucleosomal DNA binding (GO:0031492)

GO Cellular Component (14): histone deacetylase complex (GO:0000118), chromosome, telomeric region (GO:0000781), chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytosol (GO:0005829), NuRD complex (GO:0016581), NURF complex (GO:0016589), protein-containing complex (GO:0032991), CAF-1 complex (GO:0033186), ESC/E(Z) complex (GO:0035098), Sin3-type complex (GO:0070822), ATPase complex (GO:1904949), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-17 pathways:

Category	Pathways
G0 and Early G1	2
Chromatin modifying enzymes	2
G1/S Transition	2
Mitotic G1 phase and G1/S transition	1
G2/M Transition	1
Epigenetic regulation of gene expression	1
Cellular Senescence	1
Positive epigenetic regulation of rRNA expression	1
Activation of HOX genes during differentiation	1
Nucleosome assembly	1
Regulation of TP53 Activity	1
S Phase	1
RNA Polymerase I Promoter Clearance	1
PTEN Regulation	1
Generic Transcription Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chromatin organization	3
DNA-templated transcription	3
cellular anatomical structure	3
DNA metabolic process	2
regulation of DNA-templated transcription	2
stem cell population maintenance	2
regulation of stem cell population maintenance	2
catalytic complex	2
histone deacetylase complex	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
negative regulation of DNA-templated transcription	1
DNA biosynthetic process	1
DNA damage response	1
nucleosome organization	1
protein-DNA complex assembly	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
central nervous system development	1
animal organ development	1
head development	1
cell population proliferation	1
regulation of cell population proliferation	1
negative regulation of cellular process	1
cell migration	1
regulation of cell migration	1
negative regulation of cell motility	1
transforming growth factor beta receptor signaling pathway	1
regulation of transforming growth factor beta receptor signaling pathway	1
negative regulation of transmembrane receptor protein serine/threonine kinase signaling pathway	1
cell fate specification	1
regulation of cell fate commitment	1
negative regulation of RNA biosynthetic process	1
positive regulation of RNA biosynthetic process	1
negative regulation of developmental process	1
negative regulation of multicellular organismal process	1
positive regulation of developmental process	1
positive regulation of multicellular organismal process	1
regulation of cell differentiation	1
stem cell differentiation	1

Protein interactions and networks

STRING

0 interactions, top by confidence (×1000):

IntAct

370 interactions, top by confidence:

A	B	Type	Score
HDAC1	MTA2	psi-mi:“MI:0403”(colocalization)	0.950
MTA1	RBBP4	psi-mi:“MI:0915”(physical association)	0.930
RBBP4	MTA1	psi-mi:“MI:0915”(physical association)	0.930
HDAC1	RBBP4	psi-mi:“MI:0914”(association)	0.920
SUZ12	EED	psi-mi:“MI:0914”(association)	0.910
HDAC1	KDM1A	psi-mi:“MI:0914”(association)	0.910
DSN1	ZWINT	psi-mi:“MI:0914”(association)	0.900
MTA2	RBBP4	psi-mi:“MI:0914”(association)	0.890
EED	RBBP4	psi-mi:“MI:0914”(association)	0.840
H3C1	RBBP4	psi-mi:“MI:0914”(association)	0.840
HAT1	RBBP4	psi-mi:“MI:0915”(physical association)	0.800
RBBP4	HAT1	psi-mi:“MI:0915”(physical association)	0.800
CHAF1B	RBBP4	psi-mi:“MI:0914”(association)	0.790
CHD3	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
PHF1	EED	psi-mi:“MI:0914”(association)	0.790
RBBP4	CDK2AP1	psi-mi:“MI:0914”(association)	0.790
SMARCA1	RBBP4	psi-mi:“MI:0914”(association)	0.770
SMARCA1	RBBP4	psi-mi:“MI:0915”(physical association)	0.770
H3C1	HAT1	psi-mi:“MI:0914”(association)	0.770
BPTF	SMARCA1	psi-mi:“MI:0914”(association)	0.750

BioGRID (1534): RBBP4 (Affinity Capture-Western), RBBP4 (Affinity Capture-MS), RBBP4 (Affinity Capture-MS), HAT1 (Two-hybrid), MTA1 (Two-hybrid), RBBP4 (Affinity Capture-Western), RBBP4 (Affinity Capture-Western), PHF6 (Affinity Capture-Western), RBBP4 (Affinity Capture-MS), RBBP4 (Affinity Capture-MS), RBBP4 (Affinity Capture-MS), RBBP4 (Protein-peptide), RBBP4 (Affinity Capture-MS), RBBP4 (Affinity Capture-MS), RBBP4 (Affinity Capture-MS)

ESM2 similar proteins: A0A324, A1XQR9, A4FUI2, A5JSS2, A6MZM2, G1SHQ2, O09167, O14602, O35900, O60739, P20280, P25800, P41567, P46778, P47813, P48024, P49666, P51971, P61220, P62303, P62304, P62305, P62308, P62309, Q09028, Q0D5W6, Q0P5B3, Q2KIA3, Q3B8H4, Q3ZBL0, Q4R4X9, Q503U0, Q5E938, Q5RA42, Q5RBW7, Q5RFF4, Q60872, Q60972, Q6GVM3, Q6QN05

Diamond homologs: A1CUD6, A2AH22, A7TLU2, A8IZG4, A8X8C6, B0R0D7, B0XAF3, B4GDM7, B4JW81, B4LJT7, E7FAG6, F1LTR1, G0SA60, G0SC29, O13046, O13923, O22468, O75717, O76071, O93377, O94527, P0CS38, P0CS39, P0DPA1, P25382, P25569, P26309, P57737, Q06440, Q08E38, Q09028, Q16576, Q1DZQ0, Q24572, Q28D01, Q28DW0, Q292E8, Q3MHL3, Q3SWX8, Q4KLI9

SIGNOR signaling

4 interactions.

A	Effect	B	Mechanism
RBBP4	“form complex”	“Polycomb repressive complex 2”	binding
RBBP4	“form complex”	“MBD2/NuRD complex”	binding
RBBP4	“form complex”	“MBD3/NuRD complex”	binding
RBBP4	“form complex”	HNuRF	binding

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 152 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
Transcriptional regulation of brown and beige adipocyte differentiation by EBF2	8	25.8×	8e-08
Transcription of E2F targets under negative control by p107 (RBL1) and p130 (RBL2) in complex with HDAC1	5	25.5×	4e-05
Regulation of TP53 Activity through Acetylation	6	23.2×	8e-06
Transcription of E2F targets under negative control by DREAM complex	5	23.0×	6e-05
G0 and Early G1	6	22.3×	9e-06
Regulation of PTEN gene transcription	14	21.2×	8e-13
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	16	19.9×	5e-14
PTEN Regulation	8	15.5×	2e-06

GO biological processes:

GO term	Partners	Fold	FDR
regulation of stem cell differentiation	7	38.6×	8e-08
positive regulation of protein import into nucleus	7	21.2×	7e-06
negative regulation of gene expression, epigenetic	5	14.4×	2e-03
epigenetic regulation of gene expression	5	13.8×	3e-03
response to nutrient levels	5	13.2×	3e-03
chromatin remodeling	22	11.6×	3e-14
nucleosome assembly	9	9.1×	8e-05
chromatin organization	9	6.4×	1e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	19
Likely benign	0
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

2371 predictions. Top by Δscore:

Variant	Effect	Δscore
1:32651320:A:T	donor_gain	1.0000
1:32651906:A:G	acceptor_gain	1.0000
1:32651912:A:AG	acceptor_gain	1.0000
1:32651913:G:GC	acceptor_gain	1.0000
1:32651913:GC:G	acceptor_gain	1.0000
1:32651913:GCA:G	acceptor_gain	1.0000
1:32651913:GCAGC:G	acceptor_gain	1.0000
1:32652057:ACCAG:A	donor_gain	1.0000
1:32652058:CCAGG:C	donor_loss	1.0000
1:32652059:CAG:C	donor_loss	1.0000
1:32652061:GGTG:G	donor_loss	1.0000
1:32652063:T:A	donor_loss	1.0000
1:32657426:GACCA:G	acceptor_gain	1.0000
1:32657569:GGAG:G	donor_gain	1.0000
1:32657570:G:GT	donor_gain	1.0000
1:32668223:A:AG	acceptor_gain	1.0000
1:32668224:G:GG	acceptor_gain	1.0000
1:32668789:G:GT	donor_gain	1.0000
1:32668823:G:GG	donor_gain	1.0000
1:32668969:A:AG	acceptor_gain	1.0000
1:32668970:A:G	acceptor_gain	1.0000
1:32668971:G:GG	acceptor_gain	1.0000
1:32668971:GACC:G	acceptor_gain	1.0000
1:32669130:GAT:G	donor_gain	1.0000
1:32669133:G:GG	donor_gain	1.0000
1:32669224:A:AG	acceptor_gain	1.0000
1:32669224:ACT:A	acceptor_gain	1.0000
1:32669226:T:A	acceptor_gain	1.0000
1:32669229:A:AG	acceptor_gain	1.0000
1:32669229:AGTT:A	acceptor_gain	1.0000

AlphaMissense

2838 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:32651955:G:A	E20K	1.000
1:32651958:T:C	Y21H	1.000
1:32651958:T:G	Y21D	1.000
1:32651959:A:G	Y21C	1.000
1:32651963:A:C	K22N	1.000
1:32651963:A:T	K22N	1.000
1:32651965:T:A	I23K	1.000
1:32651965:T:G	I23R	1.000
1:32651967:T:A	W24R	1.000
1:32651967:T:C	W24R	1.000
1:32651968:G:C	W24S	1.000
1:32651969:G:C	W24C	1.000
1:32651969:G:T	W24C	1.000
1:32651970:A:G	K25E	1.000
1:32651971:A:T	K25I	1.000
1:32651972:A:C	K25N	1.000
1:32651972:A:T	K25N	1.000
1:32651975:G:C	K26N	1.000
1:32651975:G:T	K26N	1.000
1:32651976:A:G	N27D	1.000
1:32651977:A:T	N27I	1.000
1:32651978:C:A	N27K	1.000
1:32651978:C:G	N27K	1.000
1:32651985:T:C	F30L	1.000
1:32651986:T:C	F30S	1.000
1:32651986:T:G	F30C	1.000
1:32651987:T:A	F30L	1.000
1:32651987:T:G	F30L	1.000
1:32651989:T:A	L31H	1.000
1:32651989:T:C	L31P	1.000

dbSNP variants (sampled 300 via entrez): RS1000012005 (1:32670642 G>A), RS1000033074 (1:32681044 A>G), RS1000078286 (1:32662113 T>C), RS1000120357 (1:32665098 C>T), RS1000276909 (1:32659119 TTATA>T,TTA), RS1000317065 (1:32675785 A>G), RS1000343098 (1:32675668 C>G,T), RS1000404806 (1:32660483 C>G), RS1000441079 (1:32655071 C>A), RS1000521395 (1:32679549 ACT>A), RS1000563104 (1:32666439 A>C,G), RS1000627128 (1:32661513 C>T), RS1000632916 (1:32665344 A>G), RS1000706858 (1:32685312 A>G), RS1000749843 (1:32664236 A>G,T)

Disease associations

OMIM: gene MIM:602923 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

0 associations (top):

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (6): CHEMBL2189120 (SINGLE PROTEIN), CHEMBL3137287 (PROTEIN COMPLEX), CHEMBL3301388 (PROTEIN COMPLEX), CHEMBL6066550 (PROTEIN COMPLEX), CHEMBL6066551 (PROTEIN COMPLEX), CHEMBL6066587 (PROTEIN COMPLEX)

Molecules with ChEMBL bioactivity

1 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 1,869 (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
CHEMBL3414621	TAZEMETOSTAT	4	1,869

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

Binding affinities (BindingDB)

89 measured of 144 human assays (144 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
5-[(E)-1-(4-aminocyclohexyl)prop-1-enyl]-N-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methyl]-4-methylthiophene-3-carboxamide	IC50	13 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(((cis)-4-(dimethylamino)cyclohexyl)(ethyl)amino)-4-methylthiophene-3-carboxamide (Example 7) and N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(((trans)-4-(dimethylamino)cyclohexyl)(ethyl)amino)-4-methylthiophene-3-carboxamide (Example 8)	IC50	13 nM	US-9790212: Enhancer of zeste homolog 2 inhibitors
5-Bromo-3-(sec-butoxy)-N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-2-methylbenzamide	IC50	13 nM	US-10478426: Enhancer of Zeste Homolog 2 inhibitors
4-[[4-(dimethylamino)cyclohexyl]-ethylamino]-N-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methyl]-3-methylthiophene-2-carboxamide	IC50	16 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
N-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methyl]-5-[ethyl(oxan-4-yl)amino]-4-methylthiophene-3-carboxamide	IC50	16 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
tert-butyl 4-[[4-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methylcarbamoyl]-3-methylthiophen-2-yl]-ethylamino]piperidine-1-carboxylate	IC50	16 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
5-[1-(4-aminocyclohexyl)propyl]-N-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methyl]-4-methylthiophene-3-carboxamide	IC50	16 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
2-chloro-N-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methyl]-5-[ethyl(oxan-4-yl)amino]-4-methylthiophene-3-carboxamide	IC50	16 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
N-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methyl]-5-[ethyl-[4-[ethyl(methyl)amino]cyclohexyl]amino]-4-methylthiophene-3-carboxamide	IC50	16 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
5-[1-[4-(dimethylamino)piperidin-1-yl]propyl]-N-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methyl]-4-methylthiophene-3-carboxamide	IC50	19 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
N-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methyl]-5-[ethyl(piperidin-4-yl)amino]-4-methylthiophene-3-carboxamide	IC50	20 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
2-bromo-N-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methyl]-5-[ethyl(oxan-4-yl)amino]-4-methylthiophene-3-carboxamide	IC50	20 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
N-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methyl]-4-methyl-5-(1-piperidin-4-ylpropyl)thiophene-3-carboxamide	IC50	20 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
5-[(1S)-1-[4-(dimethylamino)piperidin-1-yl]propyl]-N-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methyl]-4-methylthiophene-3-carboxamide	IC50	20 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
5-[1-[4-(dimethylamino)cyclohexyl]propyl]-N-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methyl]-4-methylthiophene-3-carboxamide	IC50	20 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
2-bromo-5-[[4-(dimethylamino)cyclohexyl]-ethylamino]-N-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methyl]-4-methylthiophene-3-carboxamide	IC50	20 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
N-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methyl]-5-[ethyl-(3-fluoropiperidin-4-yl)amino]-4-methylthiophene-3-carboxamide	IC50	20 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
2-cyano-5-[[4-(dimethylamino)cyclohexyl]-ethylamino]-N-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methyl]-4-methylthiophene-3-carboxamide	IC50	25 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
N-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methyl]-5-[ethyl(oxan-4-yl)amino]-2-(furan-3-yl)-4-methylthiophene-3-carboxamide	IC50	25 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
5-[1-[4-(dimethylamino)piperidin-1-yl]ethyl]-N-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methyl]-4-methylthiophene-3-carboxamide	IC50	31 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
4-[[4-(dimethylamino)cyclohexyl]-ethylamino]-N-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methyl]-3-methylthiophene-2-carboxamide	IC50	32 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
N-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methyl]-5-[ethyl(oxan-4-yl)amino]-2,4-dimethylthiophene-3-carboxamide	IC50	32 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
N-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methyl]-5-[ethyl(oxan-4-yl)amino]-2-(furan-2-yl)-4-methylthiophene-3-carboxamide	IC50	32 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
5-[[4-(dimethylamino)cyclohexyl]-ethylamino]-N-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methyl]-2-(furan-3-yl)-4-methylthiophene-3-carboxamide	IC50	32 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
5-[[4-(dimethylamino)cyclohexyl]-ethylamino]-4-methyl-N-[(1,4,6-trimethyl-2-oxo-3-pyridinyl)methyl]thiophene-3-carboxamide	IC50	50 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
tert-butyl 4-[1-[4-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methylcarbamoyl]-3-methylthiophen-2-yl]propyl]piperidine-1-carboxylate	IC50	50 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
N-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methyl]-5-[ethyl-(1-propan-2-ylpiperidin-4-yl)amino]-4-methylthiophene-3-carboxamide	IC50	63 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
2-cyano-N-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methyl]-5-[ethyl(oxan-4-yl)amino]-4-methylthiophene-3-carboxamide	IC50	79 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
N-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methyl]-4-methyl-5-(2-piperidin-4-ylpyrrolidin-1-yl)thiophene-3-carboxamide	IC50	79 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
5-chloro-N-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methyl]-4-[ethyl(oxan-4-yl)amino]-3-methylthiophene-2-carboxamide	IC50	100 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
N-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methyl]-5-[hydroxy(piperidin-4-yl)methyl]-4-methylthiophene-3-carboxamide	IC50	100 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
N-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methyl]-4-methyl-5-(2-methylpyrrolidin-1-yl)thiophene-3-carboxamide	IC50	100 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
5-[ethyl(oxan-4-yl)amino]-4-methyl-N-[(1,4,6-trimethyl-2-oxo-3-pyridinyl)methyl]thiophene-3-carboxamide	IC50	100 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
tert-butyl N-[4-[(E)-1-[4-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methylcarbamoyl]-3-methylthiophen-2-yl]prop-1-enyl]cyclohexyl]carbamate	IC50	100 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
N-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methyl]-4-methyl-5-(1,2,3,4-tetrahydroisoquinolin-5-yl)thiophene-3-carboxamide	IC50	100 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
N-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methyl]-5-[ethyl(oxan-4-yl)amino]-4-methyl-2-(1-methylpyrazol-4-yl)thiophene-3-carboxamide	IC50	100 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-(hydroxy(piperidin-4-yl)methyl)-4-methylthiophene-3-carboxamide	IC50	100 nM	US-9790212: Enhancer of zeste homolog 2 inhibitors
N-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methyl]-4-methyl-5-(1-piperidin-4-ylethenyl)thiophene-3-carboxamide	IC50	126 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
N-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methyl]-4-methyl-5-[6-(4-methylpiperazin-1-yl)hexan-3-yl]thiophene-3-carboxamide	IC50	126 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
tert-butyl 4-[hydroxy-(4-methoxycarbonyl-3-methylthiophen-2-yl)methyl]piperidine-1-carboxylate	IC50	158 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
5-[[4-(dimethylamino)cyclohexyl]-hydroxymethyl]-N-[(4,6-dimethyl-2-oxo-3H-pyridin-3-yl)methyl]-4-methylthiophene-3-carboxamide	IC50	158 nM	US-9505745: Enhancer of zeste homolog 2 inhibitors
5-[5-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylamino]pyrido[3,4-d]pyridazin-8-yl]-N,N,4-trimethylpyridine-2-carboxamide	IC50	175 nM	US-12421228: Naphthyridine derivatives as PRC2 inhibitors
4-[5-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylamino]pyrido[3,4-d]pyridazin-8-yl]-N,N-dimethylbenzamide	IC50	175 nM	US-12421228: Naphthyridine derivatives as PRC2 inhibitors
N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)-8-(4-((methylamino)methyl)phenyl)pyrido[3,4-d]pyridazin-5-amine	IC50	175 nM	US-12421228: Naphthyridine derivatives as PRC2 inhibitors
N-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methyl]-4-(2-methyl-4-methylsulfonylphenyl)-2,7-naphthyridin-1-amine	IC50	175 nM	US-12421228: Naphthyridine derivatives as PRC2 inhibitors
5-(1-(((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)amino)-2,7-naphthyridin-4-yl)-N,N,1-trimethyl-1H-pyrazol-e-3-carboxamide	IC50	175 nM	US-12421228: Naphthyridine derivatives as PRC2 inhibitors
4-(1,3-dimethyl-1H-pyrazol-5-yl)-N-((5-fluoro-2,3-dihydrobenzofuran-4-yl)methyl)-6-methoxy-2,7-naphthyridin-1-amine	IC50	175 nM	US-12421228: Naphthyridine derivatives as PRC2 inhibitors
8-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylamino]-5-[4-(pyrrolidin-1-ylmethyl)phenyl]-2H-2,7-naphthyridin-3-one	IC50	175 nM	US-12421228: Naphthyridine derivatives as PRC2 inhibitors
5-[4-[(dimethylamino)methyl]phenyl]-8-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylamino]-2H-2,7-naphthyridin-3-one	IC50	175 nM	US-12421228: Naphthyridine derivatives as PRC2 inhibitors
8-[(5-fluoro-2,3-dihydro-1-benzofuran-4-yl)methylamino]-5-(2-methyl-4-methylsulfonylphenyl)-2H-2,7-naphthyridin-3-one	IC50	175 nM	US-12421228: Naphthyridine derivatives as PRC2 inhibitors

ChEMBL bioactivities

587 potent at pChembl≥5 of 594 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
9.40	IC50	0.4	nM	CHEMBL4161265
9.30	IC50	0.5	nM	CHEMBL4165937
9.22	Ki	0.6	nM	CHEMBL2204997
9.22	IC50	0.6	nM	CHEMBL4160111
9.10	IC50	0.8	nM	CHEMBL4172576
8.92	Ki	1.2	nM	CHEMBL2204995
8.77	IC50	1.7	nM	CHEMBL6031570
8.67	IC50	2.15	nM	CHEMBL6052145
8.66	IC50	2.2	nM	CHEMBL5830594
8.60	IC50	2.5	nM	CHEMBL5755546
8.58	IC50	2.65	nM	CHEMBL6024531
8.57	IC50	2.7	nM	CHEMBL4164687
8.54	IC50	2.9	nM	CHEMBL4170327
8.54	IC50	2.9	nM	CHEMBL5744415
8.51	IC50	3.1	nM	CHEMBL5951235
8.49	IC50	3.2	nM	CHEMBL5921456
8.48	IC50	3.3	nM	CHEMBL4162316
8.48	IC50	3.3	nM	CHEMBL6026043
8.47	IC50	3.4	nM	CHEMBL5850167
8.46	IC50	3.5	nM	CHEMBL5757741
8.44	IC50	3.6	nM	CHEMBL5903614
8.42	IC50	3.8	nM	CHEMBL4177454
8.41	IC50	3.9	nM	CHEMBL5981172
8.40	IC50	4	nM	CHEMBL2204995
8.40	IC50	4	nM	CHEMBL2204997
8.40	IC50	4	nM	CHEMBL4162499
8.40	IC50	4	nM	CHEMBL4170753
8.40	IC50	4	nM	CHEMBL4174176
8.40	IC50	4	nM	TAZEMETOSTAT
8.39	IC50	4.1	nM	CHEMBL4169191
8.39	IC50	4.1	nM	CHEMBL5873219
8.38	IC50	4.2	nM	CHEMBL5993160
8.35	IC50	4.5	nM	CHEMBL5938838
8.34	IC50	4.6	nM	CHEMBL4169368
8.34	IC50	4.6	nM	CHEMBL4162406
8.33	IC50	4.7	nM	CHEMBL5790437
8.33	IC50	4.7	nM	CHEMBL5989347
8.32	IC50	4.8	nM	CHEMBL6020239
8.30	IC50	5	nM	CHEMBL5873219
8.28	IC50	5.3	nM	CHEMBL6019980
8.28	IC50	5.2	nM	CHEMBL5885689
8.27	IC50	5.4	nM	CHEMBL5799894
8.25	IC50	5.6	nM	CHEMBL5970917
8.23	IC50	5.9	nM	CHEMBL4169598
8.22	IC50	6	nM	CHEMBL4167587
8.21	IC50	6.1	nM	CHEMBL4169762
8.21	IC50	6.1	nM	CHEMBL5899703
8.19	IC50	6.5	nM	CHEMBL4176373
8.19	IC50	6.4	nM	CHEMBL4161444

PubChem BioAssay actives

43 with measured affinity, of 55 total; 34 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
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
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
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
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
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-[(6-methyl-2-oxo-4-propyl-1H-pyridin-3-yl)methyl]-6-[2-(4-methylpiperazin-1-yl)-4-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	0.0012	uM
6-[ethyl(oxan-4-yl)amino]-N-[(4-methoxy-6-methyl-2-oxo-1H-pyridin-3-yl)methyl]-5-methyl-2-(trifluoromethyl)-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	0.0027	uM
6-[ethyl(oxan-4-yl)amino]-N-[(4-methoxy-6-methyl-2-oxo-1H-pyridin-3-yl)methyl]-2,5-dimethyl-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	0.0029	uM
5-ethyl-6-[ethyl(oxan-4-yl)amino]-N-[(4-methoxy-6-methyl-2-oxo-1H-pyridin-3-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	0.0033	uM
N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-6-[ethyl(oxan-4-yl)amino]-2,5-dimethyl-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	0.0038	uM
N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-5-ethyl-6-[ethyl(oxan-4-yl)amino]-2-(1-propan-2-ylpiperidin-4-yl)-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	0.0040	uM
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	0.0040	uM
N-[(4,6-dimethyl-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	0.0040	uM
Tazemetostat	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	0.0040	uM
6-[ethyl(oxan-4-yl)amino]-2-fluoro-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	0.0041	uM
N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-5-ethyl-6-[ethyl(oxan-4-yl)amino]-2-(morpholin-4-ylmethyl)-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	0.0046	uM
6-[ethyl(oxan-4-yl)amino]-5-methyl-N-[[6-methyl-2-oxo-4-(trifluoromethyl)-1H-pyridin-3-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	0.0046	uM
6-[ethyl(oxan-4-yl)amino]-N-[(4-methoxy-6-methyl-2-oxo-1H-pyridin-3-yl)methyl]-3,5-dimethyl-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	0.0059	uM
N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-6-[ethyl(oxan-4-yl)amino]-5-methyl-1-benzothiophene-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	0.0060	uM
N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-5-ethyl-6-[ethyl(oxan-4-yl)amino]-2-(1-methylpiperidin-4-yl)-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	0.0061	uM
5-ethyl-6-[ethyl(oxan-4-yl)amino]-N-[(4-methoxy-6-methyl-2-oxo-1H-pyridin-3-yl)methyl]-2-(piperidin-1-ylmethyl)-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	0.0064	uM
5-chloro-6-[ethyl(oxan-4-yl)amino]-N-[(6-methyl-2-oxo-1H-pyridin-3-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	0.0065	uM
5-ethyl-6-[ethyl(oxan-4-yl)amino]-N-[(4-methoxy-6-methyl-2-oxo-1H-pyridin-3-yl)methyl]-2-(morpholin-4-ylmethyl)-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	0.0078	uM
N-[(4,6-dimethyl-2-oxo-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	0.0079	uM
N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-6-[2-(4-methylpiperazin-1-yl)-4-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	0.0140	uM
N-(furan-2-ylmethyl)-8-(4-methylsulfonylphenyl)-[1,2,4]triazolo[4,3-c]pyrimidin-5-amine	1802691: HMT Assay from Article 10.1038/nchembio.2304: “An allosteric PRC2 inhibitor targeting the H3K27me3 binding pocket of EED.”	ic50	0.0200	uM
5-bromo-N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-3-[ethyl(oxan-4-yl)amino]-2-methylbenzamide	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	0.0200	uM
6-cyclopropyl-N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-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	0.0740	uM
6-cyclopropyl-N-[(4,6-dimethyl-2-oxo-1H-pyridin-3-yl)methyl]-1-propan-2-ylpyrazolo[5,4-b]pyridine-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	0.1490	uM
(6R,7R)-6,7-dihydroxy-1,6-dimethyl-8,9-dihydro-7H-naphtho[1,2-g][1]benzofuran-10,11-dione	1151969: Competitive inhibition of EZH2 histone methyltransferase activity in EZH2/SUZ12/EED/RbAp46/48 (unknown origin) using histone H3 peptide/varying concentration of S-adenosylmethionine as substrate after 2 hrs by Lineweaver-Burk plot analysis	ki	0.1940	uM
6-[ethyl(oxan-4-yl)amino]-N-[(4-methoxy-6-methyl-2-oxo-1H-pyridin-3-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	0.3310	uM
4-methyl-3-[(2-methyl-6-pyridin-3-ylpyrazolo[3,4-d]pyrimidin-4-yl)amino]-N-[3-(trifluoromethyl)phenyl]benzamide	2149199: Binding affinity to human RBBP4 incubated for 45 mins by Kinobead based pull down assay	kd	0.4583	uM
6-[ethyl(oxan-4-yl)amino]-N-[(4-methoxy-6-methyl-2-oxo-1H-pyridin-3-yl)methyl]-5-(trifluoromethyl)-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	2.0000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases methylation	9
Tretinoin	decreases expression, increases expression	3
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression, decreases expression	2
Doxorubicin	increases expression, decreases response to substance	2
Fluorouracil	decreases expression, affects cotreatment, decreases response to substance	2
Cadmium Chloride	increases expression, increases abundance	2
FR900359	increases phosphorylation	1
bisphenol F	affects cotreatment, increases expression	1
TAK-243	increases sumoylation	1
triphenyl phosphate	affects expression	1
bisphenol A	decreases expression	1
sodium arsenate	decreases expression	1
sulforaphane	affects binding	1
tris(1,3-dichloro-2-propyl)phosphate	decreases expression	1
sodium arsenite	decreases expression	1
cobaltous chloride	decreases expression	1
butyraldehyde	decreases expression	1
perfluorooctanoic acid	decreases expression	1
ochratoxin A	decreases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	affects cotreatment, increases expression	1
epigallocatechin gallate	increases expression	1
tamibarotene	affects expression	1
di-n-butylphosphoric acid	affects expression	1
perfluorooctane sulfonic acid	decreases expression	1
perfluoro-n-nonanoic acid	decreases expression	1
entinostat	decreases expression	1
monomethylarsonous acid	increases expression	1
K 7174	decreases expression	1
perfluorohexanesulfonic acid	decreases expression	1
abrine	decreases expression	1

ChEMBL screening assays

23 unique, capped per target: 23 binding

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL5039007	Binding	Binding affinity to RbAp48 in human WSUDLCL2 cells assessed as thermal stability by measuring shift in temperature at 60 uM pretreated with proteasome inhibitor MG132 for 1 hr followed by compound addition incubated for 2 hrs by cellular th	Design and Synthesis of EZH2-Based PROTACs to Degrade the PRC2 Complex for Targeting the Noncatalytic Activity of EZH2. — J Med Chem

Clinical trials (associated diseases)

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