BRD2

Summary

BRD2 (bromodomain containing 2, HGNC:1103) is a protein-coding gene on chromosome 6p21.32, encoding Bromodomain-containing protein 2 (P25440). Chromatin reader protein that specifically recognizes and binds histone H4 acetylated at ‘Lys-5’ and ‘Lys-12’ (H4K5ac and H4K12ac, respectively), thereby controlling gene expression and remodeling chromatin structures. It is a selective cancer dependency (DepMap: 39.0% of cell lines).

This gene encodes a transcriptional regulator that belongs to the BET (bromodomains and extra terminal domain) family of proteins. This protein associates with transcription complexes and with acetylated chromatin during mitosis, and it selectively binds to the acetylated lysine-12 residue of histone H4 via its two bromodomains. The gene maps to the major histocompatability complex (MHC) class II region on chromosome 6p21.3, but sequence comparison suggests that the protein is not involved in the immune response. This gene has been implicated in juvenile myoclonic epilepsy, a common form of epilepsy that becomes apparent in adolescence. Multiple alternatively spliced variants have been described for this gene.

Source: NCBI Gene 6046 — RefSeq curated summary.

At a glance

• GWAS associations: 14
• Clinical variants (ClinVar): 184 total
• Druggable target: yes — 9 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 39.0% of screened cell lines
• MANE Select transcript: NM_005104

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1103
Approved symbol	BRD2
Name	bromodomain containing 2
Location	6p21.32
Locus type	gene with protein product
Status	Approved
Aliases	KIAA9001, RING3, D6S113E, NAT, FSHRG1
Ensembl gene	ENSG00000204256
Ensembl biotype	protein_coding
OMIM	601540
Entrez	6046

Gene structure

Transcript identifiers

Ensembl transcripts: 27 — 12 protein_coding, 6 nonsense_mediated_decay, 5 retained_intron, 4 protein_coding_CDS_not_defined

ENST00000374825, ENST00000374831, ENST00000395287, ENST00000449025, ENST00000449085, ENST00000456339, ENST00000463639, ENST00000464592, ENST00000469132, ENST00000481259, ENST00000482838, ENST00000482914, ENST00000495733, ENST00000580234, ENST00000581002, ENST00000584808, ENST00000606059, ENST00000607833, ENST00000677085, ENST00000677331, ENST00000678250, ENST00000678778, ENST00000679099, ENST00000679179, ENST00000880156, ENST00000932589, ENST00000932590

RefSeq mRNA: 5 — MANE Select: NM_005104 NM_001113182, NM_001199455, NM_001199456, NM_001291986, NM_005104

CCDS: CCDS4762, CCDS56420

Canonical transcript exons

ENST00000374825 — 13 exons

Exon	Start	End
ENSE00001743441	32968594	32969056
ENSE00003481179	32975384	32975521
ENSE00003482490	32976031	32976169
ENSE00003566932	32974462	32974765
ENSE00003574048	32976250	32976464
ENSE00003613748	32977442	32977570
ENSE00003614468	32976562	32976936
ENSE00003632261	32977757	32978005
ENSE00003645751	32979828	32980132
ENSE00003650925	32978126	32978388
ENSE00003663341	32980342	32980464
ENSE00003691002	32971595	32972927
ENSE00003846357	32980582	32981501

Expression profiles

Bgee: expression breadth ubiquitous, 134 present calls, max score 99.27.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 116.2398 / max 1210.5555, expressed in 1826 samples.

FANTOM5 promoters (20 alternative TSS)

Promoter ID	TPM avg	Samples expressed
67202	78.5511	1821
67199	11.4810	1790
67191	10.5657	1783
67197	1.9300	862
67207	1.5557	958
67193	1.5096	673
67200	1.3647	815
67198	1.3460	755
67195	1.2719	584
203961	1.0576	601

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
ventricular zone	UBERON:0003053	99.27	gold quality
granulocyte	CL:0000094	99.15	gold quality
ganglionic eminence	UBERON:0004023	99.08	gold quality
left lobe of thyroid gland	UBERON:0001120	98.79	gold quality
right testis	UBERON:0004534	98.76	gold quality
right lobe of thyroid gland	UBERON:0001119	98.75	gold quality
thyroid gland	UBERON:0002046	98.75	gold quality
left testis	UBERON:0004533	98.75	gold quality
pituitary gland	UBERON:0000007	98.72	gold quality
metanephros cortex	UBERON:0010533	98.66	gold quality
adenohypophysis	UBERON:0002196	98.65	gold quality
cortical plate	UBERON:0005343	98.62	gold quality
cerebellar hemisphere	UBERON:0002245	98.61	gold quality
cerebellum	UBERON:0002037	98.60	gold quality
cerebellar cortex	UBERON:0002129	98.60	gold quality
right hemisphere of cerebellum	UBERON:0014890	98.60	gold quality
body of pancreas	UBERON:0001150	98.56	gold quality
mucosa of stomach	UBERON:0001199	98.54	gold quality
lymph node	UBERON:0000029	98.53	gold quality
spleen	UBERON:0002106	98.51	gold quality
left ovary	UBERON:0002119	98.48	gold quality
pancreas	UBERON:0001264	98.45	gold quality
body of uterus	UBERON:0009853	98.45	gold quality
endocervix	UBERON:0000458	98.43	gold quality
left uterine tube	UBERON:0001303	98.43	gold quality
ovary	UBERON:0000992	98.39	gold quality
prostate gland	UBERON:0002367	98.35	gold quality
right ovary	UBERON:0002118	98.33	gold quality
testis	UBERON:0000473	98.31	gold quality
islet of Langerhans	UBERON:0000006	98.30	gold quality

Single-cell (SCXA)

Detected in 5 experiment(s), a significant marker in 3.

Experiment	Marker?	Max mean expression
E-GEOD-106540	yes	561.18
E-MTAB-8559	yes	193.97
E-MTAB-6379	no	290.64
E-MTAB-10137	no	239.63
E-ANND-3	no	0.00

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
BCL2
IL7R

Upstream regulators (CollecTRI, top): BRD7, E2F1, FOXC2, GLI2, MYC

miRNA regulators (miRDB)

54 targeting BRD2, 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-4283	100.00	66.42	2097
HSA-MIR-1252-5P	100.00	69.80	2774
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-3185	99.99	68.12	1959
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-4267	99.96	66.53	2368
HSA-MIR-3912-5P	99.95	66.11	925
HSA-MIR-6845-3P	99.94	66.88	1439
HSA-MIR-6721-5P	99.93	68.92	2981
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-1323	99.83	69.89	2471
HSA-MIR-6842-5P	99.80	67.54	1587
HSA-MIR-7110-5P	99.80	67.84	1712
HSA-MIR-4668-5P	99.79	70.58	3782
HSA-MIR-3150A-3P	99.76	64.44	1640
HSA-MIR-6763-5P	99.76	64.68	1767
HSA-MIR-548O-3P	99.74	69.30	2228
HSA-MIR-4699-3P	99.71	70.15	3142
HSA-MIR-4755-5P	99.71	70.34	2716
HSA-MIR-5006-3P	99.71	70.26	2728
HSA-MIR-3175	99.65	66.30	2031
HSA-MIR-17-3P	99.55	66.77	1311
HSA-MIR-510-3P	99.54	70.06	2965
HSA-MIR-3120-3P	99.54	70.28	2669
HSA-MIR-642A-5P	99.51	65.10	1152
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-143-3P	99.49	69.05	1457
HSA-MIR-4770	99.49	69.09	1451

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 39.0% of screened cell lines.

Literature-anchored findings (GeneRIF, showing 40)

• Mitogenic stimuli induce nuclear localization of Brd2 protein. (PMID:10934046)
• Brd2 protein participates in a nuclear complex that contains E2Fs. Overexpression of Brd2 protein with oncogenic ras transactivates E2F-dependent promoters of the cell cycle regulatory genes dihydrofolate reductase, cyclin D1, cyclin A and cyclin E. (PMID:10965846)
• The BRD2 gene is located within the human class II major histocompatibility complex at Chromosome 6p21.3, but appears to have no role in antigen processing, and is likely involved in signal transduction and transcription. (PMID:11983150)
• immunoblot and immunoprecipitation experiments to identify proteins interacting with Fsrg1 and RING3 (PMID:12145330)
• highly significant linkage disequilibrium between juvenile myoclonic epilepsy and a core haplotype of five single-nucleotide-polymorphism and microsatellite markers in chromosomal region 6p21 (PMID:12830434)
• B cell-restricted expression of Brd2 in transgenic mice upregulates cyclin A trancription even in mitogenically unstimulated B cells and causes lymphoma with a B1a-like immunophenotype, accompanied by peripheral B cell leukemia. (PMID:14563639)
• Brd2, a nuclear-localized protein kinase, binds to cyclin A promoter chromatin and recruits histone H4-specific acetylase activity, increasing cyclin A transcription and accelerating S phase entry in fibroblasts. (PMID:15548137)
• Evidence from transgenic mice suggests that Brd2 transactivates the cyclin A locus, and that overexpression increases cyclin A transcription, destabilizing the cell cycle. (PMID:16512664)
• Present results support evidence that photoparoxysmal response and Myoclonic Epilepsy, Juvenile share epileptogenic pathways, for which BRD2 might be an underlying susceptibility gene. (PMID:16516380)
• The results showed that BRD7 could interact with BRD2 and the region from amino acid 430 to 798 of BRD2 was critical for the interaction of BRD2 with BRD7. BRD2 mainly localizes in nucleus and BRD2 has distinct roles in initiating apoptosis. (PMID:16786191)
• there are distinct functional roles for the two bromodomain proteins RING3/Brd2 and Brd4 in LANA binding (PMID:16940503)
• Brd2 is a novel protein kinase that plays a role in cell cycle-responsive transcription, recruiting E2F1, TATA Box Binding Protein and histone acetylase activity to E2F-responsive promoters in response to mitogenic stimuli. (PMID:17111193)
• Brd2 associates with the transcription factor E2F, the Mediator components CDK8 and TRAP220, RNA polymerase II on chromatin; and associates with acetylated histone H4 through its bromodomains. (PMID:17148447)
• Two acetyllysine-binding pockets and a negatively charged secondary binding pocket, produced at the dimer interface in BRD2 bromodomain 1 (BD1), may be the unique features that allow BRD2 BD1 to selectively bind to the acetylated histone H4 tail. (PMID:17148447)
• Brd2-driven B cell lymphomas exhibit a transcriptional signature of diffuse large B cell lymphoma, and show differential expression of genes involved in normal proliferation, as well as several novel, tumor-specific genes. (PMID:17166848)
• Brd2 bromodomain 2 is monomeric in solution and dynamically interacts with H4-AcK12; additional secondary elements in the long ZA loop may be a common characteristic of BET bromodomains. (PMID:17848202)
• The second bromodomain of Brd2 binds histone H4 acetyl-lysine K12. (PMID:17848202)
• study investigated the SNP markers (rs188254, rs206781, and rs516535) in the 3’-end of the BRD2 and found no significant difference between the allele frequencies in epilepsy cases and controls (PMID:17999746)
• Results report that the double bromodomain proteins Brd2 and Brd3 associate preferentially in vivo with hyperacetylated chromatin along the entire lengths of transcribed genes. (PMID:18406326)
• no difference was observed in the allele and genotype frequencies of BRD2 between juvenile myoclonic epilepsy (JME) and controls (PMID:19953286)
• Studies indicate that KSHV LANA interacts with Brd2 and Brd4. (PMID:20036832)
• Data report the crystal structures of the N-terminal bromodomain of human BRD2 (BRD2-BD1; residues 74-194) in complex with each of three different Lys-12-acetylated histone H4 peptides. (PMID:20048151)
• the crystal structure of the second bromodomain of BRD2 (BRD2-BD2) in complex with the di-acetylated histone H4 tail (H4K5ac/K12ac) was shown. (PMID:20709061)
• The bromodomain-containing gene BRD2 is regulated at transcription, splicing, and translation levels. (PMID:21608014)
• The BRDT gene was not expressed in testicular tissue from patients with Sertoli cells only, whereas the other three genes of the BET family retained expression in all the sperm pathologies. (PMID:22035730)
• Our study did not confirm the presence of the genetic variants previously found to link the BRD2 gene to the idiopathic form of photosensitive epilepsy. (PMID:22766109)
• Brd2 and Brd4 proteins mediatE the responses of LFs after growth factor stimulation and drivE the induction of lung fibrosis in mice in response to bleomycin challenge. (PMID:23115324)
• our results identify BRD2 as a new Tat-independent suppressor of HIV transcription in latently infected cells and underscore the therapeutic potential of BET inhibitors in the reversal of HIV latency. (PMID:23255218)
• The SNP alleles in BRD2, Cx-36, and ME2 and microdeletions in 15q13.3, 15q11.2, and 16p13.11 also contribute risk to juvenile myoclonic epilepsy’ (PMID:23756480)
• The C-terminal domain of Brd2 is important for chromatin interaction and regulation of transcription and alternative splicing. (PMID:24048450)
• BRD2, BRD3, and BRD4 interact with gammaretroviral INs and serve as cofactors for murine leukemia virus integration. (PMID:24049186)
• A structural basis for BRD2/4-mediated host chromatin interaction and oligomer assembly of Kaposi sarcoma-associated herpesvirus and murine gammaherpesvirus LANA proteins. (PMID:24146614)
• BET proteins, particularly Brd2 and Brd4, may play a key role in the regulation of Nrf2-dependent antioxidant gene transcription and are hence an important target for augmenting antioxidant responses in oxidative stress-mediated diseases. (PMID:24733848)
• An unexpected role for the bromodomain and extraterminal domain (BET) proteins BRD2 and BRD4 in maintaining oncogenic IKK activity in activated B-cell-like diffuse large B-cell lymphoma. (PMID:25049379)
• This study implicates BET Brds as important regulators of IkappaB kinase/NF-kappaB-mediated synovial inflammation of RA and identifies BET proteins as novel therapeutic targets in inflammatory arthritis. (PMID:26324948)
• LRP1B, BRD2 and CACNA1D are new candidate genes in fetal metabolic programming of newborns exposed to maternal hyperglycemia. (PMID:26586120)
• The identification of RNF43 mutations in a distinct subset of intraductal papillary neoplasm of the bile ducts revealed a new molecular role in the pathogenesis of this disease (PMID:27864998)
• In pluripotent cells, Brd2-Brd4 occupy Nodal gene regulatory elements (NREs), but only Brd4 is required for pluripotency gene expression. Brd4 downregulation facilitates pluripotent exit and drives enhanced Brd2 NRE occupancy, thereby unveiling a specific function for Brd2 in differentiative Nodal-Smad2 signalling (PMID:28588073)
• BRDs are overexpressed in castration-resistant prostate cancer and that ATAD2 and BRD2 have prognostic value. (PMID:28591577)
• The bromodomain and extraterminal domain (BET) family consists of BRDT, BRD2, BRD3, and BRD4, each containing 2 bromodomains located N-terminal to extraterminal domain, which is located near C-terminus. Data suggest that 10 distinct acylations participate in binding of BET family proteins to histone 4 (oligopeptide fragments used here); C-terminal bromodomains do not cooperatively bind multiple acylation sites. (PMID:28945351)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	brd2a	ENSDARG00000022280
danio_rerio	brd2b	ENSDARG00000046087
mus_musculus	Brd2	ENSMUSG00000024335
rattus_norvegicus	Brd2	ENSRNOG00000000461
drosophila_melanogaster	tbrd-1	FBGN0039124

Paralogs (11): BAZ1B (ENSG00000009954), BAZ2A (ENSG00000076108), CECR2 (ENSG00000099954), KAT2A (ENSG00000108773), KAT2B (ENSG00000114166), BAZ2B (ENSG00000123636), BRDT (ENSG00000137948), BRD4 (ENSG00000141867), BRD3 (ENSG00000169925), BPTF (ENSG00000171634), BAZ1A (ENSG00000198604)

Protein

Protein identifiers

Bromodomain-containing protein 2 — P25440 (reviewed: P25440)

Alternative names: O27.1.1

All UniProt accessions (8): E9PIQ3, E9PKQ9, H0Y6K2, H0Y799, H0YDJ7, P25440, U3KPW0, U3KQA6

UniProt curated annotations — full annotation on UniProt →

Function. Chromatin reader protein that specifically recognizes and binds histone H4 acetylated at ‘Lys-5’ and ‘Lys-12’ (H4K5ac and H4K12ac, respectively), thereby controlling gene expression and remodeling chromatin structures. Recruits transcription factors and coactivators to target gene sites, and activates RNA polymerase II machinery for transcriptional elongation. Plays a key role in genome compartmentalization via its association with CTCF and cohesin: recruited to chromatin by CTCF and promotes formation of topologically associating domains (TADs) via its ability to bind acetylated histones, contributing to CTCF boundary formation and enhancer insulation. Also recognizes and binds acetylated non-histone proteins, such as STAT3. Involved in inflammatory response by regulating differentiation of naive CD4(+) T-cells into T-helper Th17: recognizes and binds STAT3 acetylated at ‘Lys-87’, promoting STAT3 recruitment to chromatin. In addition to acetylated lysines, also recognizes and binds lysine residues on histones that are both methylated and acetylated on the same side chain to form N6-acetyl-N6-methyllysine (Kacme), an epigenetic mark of active chromatin associated with increased transcriptional initiation. Specifically binds histone H4 acetyl-methylated at ‘Lys-5’ and ‘Lys-12’ (H4K5acme and H4K12acme, respectively).

Subunit / interactions. Homodimer. Interacts with E2F1. Interacts with (acetylated) STAT3; promoting STAT3 recruitment to chromatin. Interacts with CTCF; promoting BRD2 recruitment to chromatin. (Microbial infection) Interacts with herpes virus 8 protein LANA1.

Subcellular location. Nucleus. Chromosome.

Activity regulation. Inhibited by JQ1, a thieno-triazolo-1,4-diazepine derivative, which specifically inhibits members of the BET family (BRD2, BRD3 and BRD4). The first bromo domain is inhibited by GSK778 (iBET-BD1), which specifically inhibits the first bromo domain of members of the BET family (BRD2, BRD3 and BRD4). The second bromo domain is inhibited by ABBV-744, which specifically inhibits the second bromo domain of members of the BET family (BRD2, BRD3 and BRD4). The second bromo domain is inhibited by GSK046 (iBET-BD2), which specifically inhibits the second bromo domain of members of the BET family (BRD2, BRD3 and BRD4).

Domain organisation. The first bromo domain specifically recognizes histone H4 acetylated at ‘Lys-12’ (H4K12ac). It also specifically binds histone H4 acetyl-methylated at ‘Lys-5’ and ‘Lys-12’ (H4K5acme and H4K12acme, respectively). The second bromo domain recognizes and binds histone H4 acetylated at ‘Lys-5’ and ‘Lys-12’ (H4K5ac and H4K12ac, respectively).

Miscellaneous. Some specific inhibitors of BRD2 that prevent binding to acetylated histone are promising therapeutic molecules for the treatment of cancers or inflammatory diseases. ABBV-744, a small molecule, has been tested on tumors with success: ABBV-744 antiproliferative activity is mainly restricted to cell lines of acute myeloid leukaemia and prostate cancer and is able to displace BRD4 from chromatin. GSK046 (iBET-BD2), which specifically inhibits the second bromo domain, is a promising therapeutic small molecule for the treatment of inflammatory and autoimmune diseases.

Similarity. Belongs to the BET family.

Isoforms (4)

UniProt ID	Names	Canonical?
P25440-1	1	yes
P25440-2	2
P25440-3	3
P25440-4	4

RefSeq proteins (5): NP_001106653, NP_001186384, NP_001186385, NP_001278915, NP_005095* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001487	Bromodomain	Domain
IPR018359	Bromodomain_CS	Conserved_site
IPR027353	NET_dom	Domain
IPR036427	Bromodomain-like_sf	Homologous_superfamily
IPR038336	NET_sf	Homologous_superfamily
IPR043508	Bromo_Brdt_I	Domain
IPR043509	Bromo_Brdt_II	Domain
IPR050935	Bromo_chromatin_reader	Family

Pfam: PF00439, PF17035

UniProt features (94 total): helix 21, mutagenesis site 20, sequence variant 12, binding site 7, modified residue 7, compositionally biased region 6, region of interest 4, strand 4, turn 4, domain 3, splice variant 3, chain 1, sequence conflict 1, short sequence motif 1

Structure

Experimental structures (PDB)

174 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
5IG6	X-RAY DIFFRACTION	0.91
5IBN	X-RAY DIFFRACTION	0.94
6DBC	X-RAY DIFFRACTION	1.05
6DDJ	X-RAY DIFFRACTION	1.05
4J1P	X-RAY DIFFRACTION	1.08
7VRM	X-RAY DIFFRACTION	1.1
6I80	X-RAY DIFFRACTION	1.14
7VRQ	X-RAY DIFFRACTION	1.15
5O38	X-RAY DIFFRACTION	1.2
5O3I	X-RAY DIFFRACTION	1.2
7USG	X-RAY DIFFRACTION	1.2
7VS0	X-RAY DIFFRACTION	1.25
7VS1	X-RAY DIFFRACTION	1.25
6K04	X-RAY DIFFRACTION	1.25
7USH	X-RAY DIFFRACTION	1.27
6MOA	X-RAY DIFFRACTION	1.27
5XHK	X-RAY DIFFRACTION	1.28
7NPZ	X-RAY DIFFRACTION	1.28
7NQ0	X-RAY DIFFRACTION	1.3
7UU0	X-RAY DIFFRACTION	1.3
9QRK	X-RAY DIFFRACTION	1.3
7OE8	X-RAY DIFFRACTION	1.3
6WWB	X-RAY DIFFRACTION	1.31
7L9G	X-RAY DIFFRACTION	1.36
5BT5	X-RAY DIFFRACTION	1.4
5DFB	X-RAY DIFFRACTION	1.4
5HFQ	X-RAY DIFFRACTION	1.4
5O3E	X-RAY DIFFRACTION	1.4
5O3H	X-RAY DIFFRACTION	1.4
5XHE	X-RAY DIFFRACTION	1.4

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-P25440-F1	65.70	0.34

Functional residue map

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

Ligand- & substrate-binding residues (7): 112; 155; 156; 156; 157; 160; 161

Post-translational modifications (7): 1, 6, 37, 298, 301, 305, 633

Mutagenesis-validated functional residues (20):

Position	Phenotype
78	loss of homodimerization.
111–112	abolished binding to histone h4 acetylated at ’lys-12’ (h4k12ac).
112–116	abolished binding to histone h4 acetylated at ’lys-12’ (h4k12ac).
113	abolished binding to histone h4 acetylated at ’lys-12’ (h4k12ac).
142–143	loss of homodimerization.
153	loss of homodimerization.
154	partial loss of homodimerization; when associated with a-182. abolished binding to histone h4 acetylated at ’lys-12’ (h4
156–160	abolished binding to histone h4 acetylated at ’lys-12’ (h4k12ac).
156	abolished binding to histone h4 acetylated at ’lys-12’ (h4k12ac). abolished binding to histone h4 acetyl-methylated.
157–160	abolished binding to histone h4 acetylated at ’lys-12’ (h4k12ac).
158	abolished binding to histone h4 acetylated at ’lys-12’ (h4k12ac).
160	abolished binding to histone h4 acetylated at ’lys-12’ (h4k12ac).
170	loss of homodimerization.
174	loss of homodimerization.
177	loss of homodimerization.
182	partial loss of homodimerization; when associated with a-154.
376	abolished binding to histone h4 acetylated at ’lys-12’ (h4k12ac).
381	reduced binding to histone h4 acetylated at ’lys-12’ (h4k12ac).
383	reduced binding to histone h4 acetylated at ’lys-12’ (h4k12ac).
429	abolished binding to histone h4 acetylated at ’lys-12’ (h4k12ac).

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-8951936	RUNX3 regulates p14-ARF
R-HSA-212436	Generic Transcription Pathway
R-HSA-73857	RNA Polymerase II Transcription
R-HSA-74160	Gene expression (Transcription)
R-HSA-8878159	Transcriptional regulation by RUNX3

MSigDB gene sets: 391 (showing top): GOBP_MORPHOGENESIS_OF_AN_EPITHELIUM, GOBP_REGULATION_OF_CELL_ACTIVATION, BROWNE_HCMV_INFECTION_4HR_UP, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, GOBP_POSITIVE_REGULATION_OF_CELL_FATE_COMMITMENT, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, ENK_UV_RESPONSE_KERATINOCYTE_UP, MORF_UBE2I, GOBP_ALPHA_BETA_T_CELL_DIFFERENTIATION, ASTON_MAJOR_DEPRESSIVE_DISORDER_DN

GO Biological Process (13): neural tube closure (GO:0001843), nucleosome assembly (GO:0006334), chromatin remodeling (GO:0006338), regulation of transcription by RNA polymerase II (GO:0006357), spermatogenesis (GO:0007283), protein localization to chromatin (GO:0071168), chromatin looping (GO:0140588), positive regulation of T-helper 17 cell lineage commitment (GO:2000330), chromatin organization (GO:0006325), regulation of DNA-templated transcription (GO:0006355), cell surface receptor signaling pathway via JAK-STAT (GO:0007259), regulation of gene expression (GO:0010468), T-helper 17 cell lineage commitment (GO:0072540)

GO Molecular Function (9): chromatin binding (GO:0003682), protein serine/threonine kinase activity (GO:0004674), histone binding (GO:0042393), histone H4K12ac reader activity (GO:0140011), histone H4K5ac reader activity (GO:0140012), histone H3K14ac reader activity (GO:0140015), acetylation-dependent protein binding (GO:0140033), protein binding (GO:0005515), protein-macromolecule adaptor activity (GO:0030674)

GO Cellular Component (6): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), nuclear speck (GO:0016607), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-4 pathways:

Category	Pathways
Transcriptional regulation by RUNX3	1
RNA Polymerase II Transcription	1
Gene expression (Transcription)	1
Generic Transcription Pathway	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
chromatin organization	3
cellular anatomical structure	3
binding	2
protein binding	2
histone H4 reader activity	2
primary neural tube formation	1
tube closure	1
nucleosome organization	1
protein-DNA complex assembly	1
regulation of DNA-templated transcription	1
transcription by RNA polymerase II	1
developmental process involved in reproduction	1
male gamete generation	1
protein localization to chromosome	1
positive regulation of cell fate commitment	1
T-helper 17 cell lineage commitment	1
positive regulation of T-helper 17 cell differentiation	1
regulation of T-helper 17 cell lineage commitment	1
cellular component organization	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
cell surface receptor signaling pathway via STAT	1
gene expression	1
regulation of macromolecule biosynthetic process	1
T-helper cell lineage commitment	1
T-helper 17 cell differentiation	1
protein kinase activity	1
histone H3 reader activity	1
modification-dependent protein binding	1
molecular adaptor activity	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
intracellular anatomical structure	1
nuclear ribonucleoprotein granule	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

2602 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BRD2	H4C16	P02304	979
BRD2	H4C7	Q99525	979
BRD2	BRD3	Q15059	952
BRD2	BRDT	Q58F21	907
BRD2	CDK9	P50750	898
BRD2	CCNT1	O60563	868
BRD2	HLA-DMA	P28067	860
BRD2	E2F1	Q01094	840
BRD2	DEFB1	P60022	838
BRD2	HLA-DOA	P06340	834
BRD2	NSD3	Q9BZ95	800
BRD2	H3-3A	P06351	798
BRD2	H3C1	P02295	798
BRD2	H3C14	Q71DI3	797
BRD2	H3-5	Q6NXT2	797
BRD2	H3-4	Q16695	797

IntAct

91 interactions, top by confidence:

A	B	Type	Score
FAM90A1	BRD4	psi-mi:“MI:2364”(proximity)	0.760
AR	BRD4	psi-mi:“MI:0914”(association)	0.680
FAM90A1	KPNA3	psi-mi:“MI:0914”(association)	0.670
CAMKV	AP3B1	psi-mi:“MI:0914”(association)	0.640
CSNK2B	RPS6KA4	psi-mi:“MI:0914”(association)	0.640
JARID2	EED	psi-mi:“MI:0914”(association)	0.640
BRD2	RUNX3	psi-mi:“MI:0915”(physical association)	0.600
RUNX3	BRD2	psi-mi:“MI:0915”(physical association)	0.600
RUNX3	BRD2	psi-mi:“MI:0914”(association)	0.600
BRD2	RUNX3	psi-mi:“MI:0403”(colocalization)	0.600
BRD2	H4C16	psi-mi:“MI:0407”(direct interaction)	0.560
E	AP3B1	psi-mi:“MI:0914”(association)	0.530
FAM90A1	RFPL4A	psi-mi:“MI:0914”(association)	0.530
PIP4K2A	AP3B1	psi-mi:“MI:0914”(association)	0.530
PES1	AP3B1	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
MDK	SETD1A	psi-mi:“MI:0914”(association)	0.530
EPB41L5	SETD1A	psi-mi:“MI:0914”(association)	0.530
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410

BioGRID (564): BRD2 (Affinity Capture-MS), BRD2 (Affinity Capture-MS), BRD2 (Affinity Capture-MS), BRD2 (Co-fractionation), BRD2 (Proximity Label-MS), BRD2 (Proximity Label-MS), BAG1 (Affinity Capture-MS), CSNK2A1 (Affinity Capture-MS), CSNK2A2 (Affinity Capture-MS), CSNK2B (Affinity Capture-MS), EPB41L1 (Affinity Capture-MS), POLR2B (Affinity Capture-MS), BRPF1 (Affinity Capture-MS), TAGLN2 (Affinity Capture-MS), COX5A (Affinity Capture-MS)

ESM2 similar proteins: A2AUY4, A6QP06, A8MW92, B7ZS37, D4A7T3, E7F888, F1QW93, F1R5H6, F7DRV9, O88665, P25440, Q03111, Q08AZ1, Q08D75, Q32S26, Q3KQW7, Q3UG20, Q4G0F8, Q4R8Y1, Q4V9H5, Q58F21, Q5DTV4, Q5HYM0, Q5R8B0, Q5TJG6, Q5ZJ69, Q6DJS0, Q6GQJ2, Q6IE81, Q6IE82, Q6MGA9, Q6P2L6, Q6ZPI0, Q7JJ13, Q801E2, Q80XI3, Q8BLG0, Q8CCJ9, Q8IZD2, Q8IZQ8

Diamond homologs: A0A0R4IXF6, A0A7U2QYM2, A2AHJ4, A2AUY4, A2BIL7, B2RRD7, B7ZS37, D4A7T3, E9Q2Z1, F1QW93, F1R5H6, F7DRV9, G5E8P1, O15164, O60885, O74350, O88379, O88665, O95696, P13709, P21675, P25440, P35817, P51123, P53236, P54816, P55201, P87152, Q02206, Q03330, Q07442, Q08D75, Q09948, Q12830, Q15059, Q1LUC3, Q23590, Q32S26, Q338B9, Q4R8Y1

SIGNOR signaling

10 interactions.

A	Effect	B	Mechanism
BRD7	“up-regulates quantity by expression”	BRD2	“transcriptional regulation”
2-[(9S)-7-(4-Chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]-N-[8-[[2-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]oxyacetyl]amino]octyl]acetamide	“down-regulates quantity”	BRD2	“chemical inhibition”
“CID 132010322”	“down-regulates activity”	BRD2	“chemical inhibition”
“Tert-butyl 2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetate”	“down-regulates activity”	BRD2	“chemical inhibition”
BRD2	“up-regulates activity”	TP53BP1	relocalization
BRD2	“up-regulates activity”	ZMYND8	relocalization
HDAC11	“down-regulates activity”	BRD2	binding
H4C1	“up-regulates activity”	BRD2	relocalization
JQ1	“down-regulates activity”	BRD2	“chemical inhibition”
2-[(4S)-6-(4-chlorophenyl)-8-methoxy-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazepin-4-yl]-N-ethylacetamide	“down-regulates activity”	BRD2	“chemical inhibition”

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
PRC2 methylates histones and DNA	6	12.9×	9e-04
SIRT1 negatively regulates rRNA expression	5	12.0×	3e-03
Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3	5	11.8×	3e-03
Inhibition of DNA recombination at telomere	5	11.8×	3e-03
Defective pyroptosis	5	11.0×	3e-03
ESR-mediated signaling	6	10.8×	2e-03
Regulation of PD-L1(CD274) transcription	7	10.7×	7e-04
Estrogen-dependent gene expression	10	10.7×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
nucleosome assembly	7	10.8×	3e-03
transcription by RNA polymerase II	8	6.2×	6e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	97
Likely benign	18
Benign	20

Top pathogenic / likely-pathogenic (0)

SpliceAI

2462 predictions. Top by Δscore:

Variant	Effect	Δscore
6:32968785:A:T	donor_gain	1.0000
6:32972928:G:GG	donor_gain	1.0000
6:32975379:TTTA:T	acceptor_loss	1.0000
6:32975381:TA:T	acceptor_loss	1.0000
6:32975382:A:AG	acceptor_gain	1.0000
6:32975383:G:GG	acceptor_gain	1.0000
6:32975519:AAGGT:A	donor_loss	1.0000
6:32975520:AGG:A	donor_loss	1.0000
6:32975521:GGT:G	donor_loss	1.0000
6:32975523:T:A	donor_loss	1.0000
6:32976014:T:A	acceptor_gain	1.0000
6:32976018:T:TA	acceptor_gain	1.0000
6:32976020:T:TA	acceptor_gain	1.0000
6:32976027:A:AG	acceptor_gain	1.0000
6:32976028:T:G	acceptor_gain	1.0000
6:32976028:TAGC:T	acceptor_loss	1.0000
6:32976029:A:AG	acceptor_gain	1.0000
6:32976029:A:C	acceptor_loss	1.0000
6:32976030:G:GG	acceptor_gain	1.0000
6:32976030:GC:G	acceptor_gain	1.0000
6:32976030:GCC:G	acceptor_gain	1.0000
6:32976030:GCCC:G	acceptor_gain	1.0000
6:32976030:GCCCA:G	acceptor_gain	1.0000
6:32976167:C:T	donor_gain	1.0000
6:32976167:CAGGT:C	donor_loss	1.0000
6:32976169:GGTAG:G	donor_loss	1.0000
6:32976170:GTAG:G	donor_loss	1.0000
6:32976171:T:G	donor_loss	1.0000
6:32976248:A:AG	acceptor_gain	1.0000
6:32976249:G:GA	acceptor_gain	1.0000

AlphaMissense

5207 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
6:32974659:C:T	T76I	1.000
6:32974668:T:C	L79P	1.000
6:32974721:T:A	W97R	1.000
6:32974721:T:C	W97R	1.000
6:32974723:G:C	W97C	1.000
6:32974723:G:T	W97C	1.000
6:32974724:C:T	P98S	1.000
6:32974725:C:A	P98Q	1.000
6:32974728:T:C	F99S	1.000
6:32974740:T:A	V103E	1.000
6:32974761:T:A	L110Q	1.000
6:32974761:T:C	L110P	1.000
6:32975387:T:A	Y113N	1.000
6:32975387:T:C	Y113H	1.000
6:32975387:T:G	Y113D	1.000
6:32975388:A:G	Y113C	1.000
6:32975400:T:A	I117K	1.000
6:32975400:T:G	I117R	1.000
6:32975414:G:C	D122H	1.000
6:32975415:A:C	D122A	1.000
6:32975415:A:T	D122V	1.000
6:32975427:T:A	I126N	1.000
6:32975435:A:G	R129G	1.000
6:32975436:G:C	R129T	1.000
6:32975436:G:T	R129I	1.000
6:32975437:A:C	R129S	1.000
6:32975437:A:T	R129S	1.000
6:32975439:T:A	L130H	1.000
6:32975439:T:C	L130P	1.000
6:32975453:T:G	Y135D	1.000

dbSNP variants (sampled 300 via entrez): RS1000069582 (6:32980805 G>A,C), RS1000231033 (6:32972171 T>A,G), RS1000266150 (6:32968746 CCCCCTTGG>C,CCCCCTTGGCCCCTTGG), RS1000313217 (6:32972733 A>G), RS1000324321 (6:32972591 C>T), RS1000519273 (6:32947520 A>G), RS1000534619 (6:32975864 A>G), RS1000575569 (6:32968900 C>A,G), RS1000789938 (6:32969088 C>T), RS1000802713 (6:32945155 G>A), RS1000823721 (6:32979680 C>T), RS1000836306 (6:32967787 T>A,C), RS1000936381 (6:32979545 A>G), RS1000984337 (6:32954725 C>A), RS1001094030 (6:32947760 C>A,T)

Disease associations

OMIM: gene MIM:601540 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

14 associations (top):

Study	Trait	p-value
GCST003958_11	Inflammatory bowel disease	2.000000e-08
GCST003958_15	Inflammatory bowel disease	9.000000e-10
GCST003958_3	Inflammatory bowel disease	5.000000e-11
GCST003959_3	Crohn’s disease	5.000000e-09
GCST003959_6	Crohn’s disease	3.000000e-06
GCST003959_9	Crohn’s disease	3.000000e-07
GCST003960_1	Ulcerative colitis	2.000000e-08
GCST003960_6	Ulcerative colitis	3.000000e-07
GCST004521_170	Autism spectrum disorder or schizophrenia	4.000000e-14
GCST004521_255	Autism spectrum disorder or schizophrenia	6.000000e-11
GCST006948_42	Feeling nervous	2.000000e-10
GCST008916_27	Asthma	5.000000e-31
GCST008916_90	Asthma	4.000000e-15
GCST010083_292	Hemoglobin levels	2.000000e-08

EFO canonical traits (2, from GWAS)

EFO ID	Trait name
EFO:0009597	feeling nervous measurement
EFO:0004509	hemoglobin measurement

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (11): CHEMBL1293289 (SINGLE PROTEIN), CHEMBL4296134 (PROTEIN-PROTEIN INTERACTION), CHEMBL4296143 (PROTEIN-PROTEIN INTERACTION), CHEMBL4296149 (PROTEIN-PROTEIN INTERACTION), CHEMBL4296614 (PROTEIN FAMILY), CHEMBL4523752 (PROTEIN-PROTEIN INTERACTION), CHEMBL5291941 (SELECTIVITY GROUP), CHEMBL5291974 (PROTEIN FAMILY), CHEMBL6193818 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195600 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

9 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 666,594 (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
CHEMBL2393130	APABETALONE	3	1,350
CHEMBL1232461	MOLIBRESIB	2	1,538
CHEMBL3581647	BIRABRESIB	2	1,546
CHEMBL3987016	MIVEBRESIB	2	773
CHEMBL4297458	EZOBRESIB	2	58
CHEMBL12543	METHYLPYRROLIDONE	1	660,155
CHEMBL4078100	AZD-5153	1	591
CHEMBL4297454	ABBV-744	1	483
CHEMBL4785363	INOBRODIB	1	100

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs17220479	BRD2		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Bromodomain kinase (BRDK) family

Most potent curated ligand interactions (16 total), top 16:

Ligand	Action	Affinity	Parameter
SIM1	Binding	10.48	pKd
ARV-771	Inhibition	8.33	pKd
GW841819X	Inhibition	7.52	pIC50
molibresib	Inhibition	7.49	pIC50
apabetalone	Antagonist	7.05	pIC50
XD14	Inhibition	6.77	pKd
ME bromodomain inhibitor	Inhibition	6.52	pKd
WNY0824	Inhibition	6.39	pIC50
I-BET151	Inhibition	6.3	pIC50
compound 38 [PMID: 24000170]	Inhibition	6.3	pIC50
compound 36 [PMID: 24000170]	Inhibition	6.0	pIC50
LY 294002	Inhibition	5.85	pKd
compound 4d [PMID: 21851057]	Inhibition	5.8	pIC50
ET bromodomain inhibitor	Inhibition	5.05	pKd
GSK852	Inhibition	5.0	pKd
BIC1	Inhibition	4.55	pKd

Binding affinities (BindingDB)

516 measured of 667 human assays (667 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(6S+2S)-PEG1 (7)	KD	0.039 nM
MTI (35)	KI	0.076 nM
4-[6-methoxy-2-methyl-4-(2-methyl-1H-indol-3-yl)-9H-pyrimido[4,5-b]indol-7-yl]-3,5-dimethyl-1,2-oxazole	KI	1.7 nM	US-9675697: BET bromodomain inhibitors and therapeutic methods using the same
N-[4-[7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-2-methyl-9H-pyrimido[4,5-b]indol-4-yl]naphthalen-1-yl]-4-methylpiperazine-1-carboxamide	KI	2.6 nM	US-9675697: BET bromodomain inhibitors and therapeutic methods using the same
4-[7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-2-methyl-9H-pyrimido[4,5-b]indol-4-yl]-N-(1-methylpiperidin-4-yl)naphthalene-1-carboxamide	KI	3.5 nM	US-9675697: BET bromodomain inhibitors and therapeutic methods using the same
4-[7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-2-methyl-9H-pyrimido[4,5-b]indol-4-yl]-N-[1-(oxetan-3-yl)piperidin-4-yl]naphthalene-1-carboxamide	KI	3.6 nM	US-9675697: BET bromodomain inhibitors and therapeutic methods using the same
[4-[7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-2-methyl-9H-pyrimido[4,5-b]indol-4-yl]naphthalen-1-yl]-(4-methylpiperazin-1-yl)methanone	KI	4.1 nM	US-9675697: BET bromodomain inhibitors and therapeutic methods using the same
4-[7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-2-methyl-9H-pyrimido[4,5-b]indol-4-yl]-N-[1-(oxan-4-yl)piperidin-4-yl]-5-propan-2-yl-1H-pyrrole-2-carboxamide	KI	4.5 nM	US-9675697: BET bromodomain inhibitors and therapeutic methods using the same
4-[7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-2-methyl-9H-pyrimido[4,5-b]indol-4-yl]-N-(1-methylpiperidin-4-yl)-5-propan-2-yl-1H-pyrrole-2-carboxamide	KI	4.9 nM	US-9675697: BET bromodomain inhibitors and therapeutic methods using the same
3-tert-butyl-5-[7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-2-methyl-9H-pyrimido[4,5-b]indol-4-yl]-N-(1-methylpiperidin-4-yl)benzamide	KI	5.2 nM	US-9675697: BET bromodomain inhibitors and therapeutic methods using the same
4-[7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-2-methyl-9H-pyrimido[4,5-b]indol-4-yl]-N-[1-(oxetan-3-yl)piperidin-4-yl]-5-propan-2-yl-1H-pyrrole-2-carboxamide	KI	6.5 nM	US-9675697: BET bromodomain inhibitors and therapeutic methods using the same
N-[4-[7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-2-methyl-9H-pyrimido[4,5-b]indol-4-yl]naphthalen-1-yl]-4-(oxetan-3-yl)piperazine-1-carboxamide	KI	7.1 nM	US-9675697: BET bromodomain inhibitors and therapeutic methods using the same
3-tert-butyl-5-[7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-2-methyl-9H-pyrimido[4,5-b]indol-4-yl]-N-[1-(oxetan-3-yl)piperidin-4-yl]benzamide	KI	7.4 nM	US-9675697: BET bromodomain inhibitors and therapeutic methods using the same
4-(6-methoxy-2-methyl-4-quinolin-4-yl-9H-pyrimido[4,5-b]indol-7-yl)-3,5-dimethyl-1,2-oxazole	KI	7.8 nM	US-9675697: BET bromodomain inhibitors and therapeutic methods using the same
4-[8-methoxy-1-(2-methyl-1H-indol-3-yl)-5H-pyrido[4,3-b]indol-7-yl]-3,5-dimethyl-1,2-oxazole	KD	10 nM	US-9675697: BET bromodomain inhibitors and therapeutic methods using the same
(3E,5R)-3-[amino(cyclopropyl)methylidene]-5-(4-chlorophenyl)-1-(3,8-dimethyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-4-methyliminopyrrolidin-2-one	IC50	11 nM	US-9624247: Pyrazolo-pyrrolidin-4-one derivatives as bet inhibitors and their use in the treatment of disease
(6R)-6-(4-chlorophenyl)-3-cyclopropyl-5-[3-(fluoromethyl)-8-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl]-1-methyl-6H-pyrrolo[3,4-d]pyrazol-4-one	IC50	11 nM	US-9624247: Pyrazolo-pyrrolidin-4-one derivatives as bet inhibitors and their use in the treatment of disease
(4R)-4-(4-chlorophenyl)-1-cyclopropyl-5-(3,8-dimethyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-3-methyl-4H-pyrrolo[3,4-d]pyrazol-6-one	IC50	12 nM	US-8975417: Pyrazolopyrrolidine derivatives and their use in the treatment of disease
2-[3-[7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-2-methyl-9H-pyrimido[4,5-b]indol-4-yl]phenyl]propan-2-ol	KI	12 nM	US-9675697: BET bromodomain inhibitors and therapeutic methods using the same
(R)-6-(4-chlorophenyl)-5-(3,8-dimethyl-[1,2,4]triazolo[4,3-b]pyridazin-6-yl)-1-isopropyl-2-methyl-5,6-dihydropyrrolo[3,4-d]imidazol-4(1H)-one	IC50	12 nM	US-9890166: Imidazopyrrolidine derivatives and their use in the treatment of disease
1-(1-acetylazetidin-3-yl)-6-(4-chlorophenyl)-3-cyclopropyl-5-(3,7-dimethyl-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one	IC50	13 nM	US-9550796: Pyrrolopyrrolone derivatives and their use as BET inhibitors
6-(4-chlorophenyl)-3-cyclopropyl-5-(3,7-dimethyl-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)-1-(1-methylazetidin-3-yl)-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one	IC50	13 nM	US-9550796: Pyrrolopyrrolone derivatives and their use as BET inhibitors
6-(4-chlorophenyl)-3-cyclopropyl-5-[3-(difluoromethyl)-8-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl]-1-methyl-6H-pyrrolo[3,4-d]pyrazol-4-one	IC50	13 nM	US-9624247: Pyrazolo-pyrrolidin-4-one derivatives as bet inhibitors and their use in the treatment of disease
(6R)-6-(4-chlorophenyl)-3-cyclopropyl-5-[3-(difluoromethyl)-8-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl]-1-methyl-6H-pyrrolo[3,4-d]pyrazol-4-one	IC50	13 nM	US-9624247: Pyrazolo-pyrrolidin-4-one derivatives as bet inhibitors and their use in the treatment of disease
(6R)-6-(4-chlorophenyl)-3-cyclopropyl-5-(3,8-dimethyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-1-[(2S)-3,3,3-trifluoro-2-hydroxypropyl]-6H-pyrrolo[3,4-d]pyrazol-4-one	IC50	13 nM	US-9624247: Pyrazolo-pyrrolidin-4-one derivatives as bet inhibitors and their use in the treatment of disease
(R)-6-(4-chlorophenyl)-5-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-6-yl)-1-isopropyl-2-(tetrahydro-2H-pyran-4-yl)-5,6-dihydropyrrolo[3,4-d]imidazol-4(1H)-one	IC50	13 nM	US-9890166: Imidazopyrrolidine derivatives and their use in the treatment of disease
(R)-6-(4-chlorophenyl)-5-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-6-yl)-1-isopropyl-2-(2-methoxypyridin-3-yl)-5,6-dihydropyrrolo[3,4-d]imidazol-4(1H)-one	IC50	13 nM	US-9890166: Imidazopyrrolidine derivatives and their use in the treatment of disease
4-[1-(3-cyclopropyl-5-methyl-1H-pyrazol-4-yl)-8-methoxy-5H-pyrido[4,3-b]indol-7-yl]-3,5-dimethyl-1,2-oxazole	KD	13 nM	US-9675697: BET bromodomain inhibitors and therapeutic methods using the same
(4R)-4-(4-chlorophenyl)-5-(1,5-dimethyl-6-oxo-3-pyridinyl)-3-methyl-1-propan-2-yl-4H-pyrrolo[3,4-d]pyrazol-6-one	IC50	14 nM	US-8975417: Pyrazolopyrrolidine derivatives and their use in the treatment of disease
(4R)-4-(4-chlorophenyl)-1-cyclopropyl-5-(3,8-dimethyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-3-ethyl-4H-pyrrolo[3,4-d]pyrazol-6-one	IC50	14 nM	US-8975417: Pyrazolopyrrolidine derivatives and their use in the treatment of disease
3-[(3S)-3-aminopiperidin-1-yl]-5-(3,5-dimethyl-1,2-oxazol-4-yl)-3-phenyl-1H-indol-2-one	IC50	14 nM	US-9393232: Substituted 5-(3,5-dimethylisoxazol-4-yl)indoline-2-ones
6-(4-chlorophenyl)-5-(3,8-di methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-3-methyl-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one	IC50	14 nM	US-9550796: Pyrrolopyrrolone derivatives and their use as BET inhibitors
6-(4-chlorophenyl)-3-cyclopropyl-5-(3,8-di methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-1-(1-methylazetidin-3-yl)-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one	IC50	14 nM	US-9550796: Pyrrolopyrrolone derivatives and their use as BET inhibitors
6-(4-chlorophenyl)-3-cyclopropyl-5-(3,8-dimethyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-1-(oxetan-3-yl)-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one	IC50	14 nM	US-9550796: Pyrrolopyrrolone derivatives and their use as BET inhibitors
(R)-6-(4-chlorophenyl)-5-(3,7-dimethyl-3H-benzo[d][1,2,3]triazol-5-yl)-3-isopropyl-2-methyl-5,6-dihydropyrrolo[3,4-d]imidazol-4(3H)-one	IC50	14 nM	US-9890166: Imidazopyrrolidine derivatives and their use in the treatment of disease
(R)-6-(4-chlorophenyl)-5-(3-(difluoromethyl)-8-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-1-isopropyl-2-(2-methoxypyridin-3-yl)-5,6-dihydropyrrolo[3,4-d]imidazol-4(1H)-one	IC50	14 nM	US-9890166: Imidazopyrrolidine derivatives and their use in the treatment of disease
(4R)-4-(4-chlorophenyl)-1-cyclopropyl-5-(1,5-dimethyl-6-oxo-3-pyridinyl)-3-methyl-4H-pyrrolo[3,4-d]pyrazol-6-one	IC50	15 nM	US-8975417: Pyrazolopyrrolidine derivatives and their use in the treatment of disease
6-(4-chlorophenyl)-3-cyclopropyl-5-(1,5-dimethyl-6-oxo-1,6-dihydropyridin-3-yl)-1-(2-methoxyethyl)-5,6-dihydropyrrolo[3,4-c]pyrazol-4(1H)-one	IC50	15 nM	US-9714249: Pyrazolo-pyrrolidin-4-one derivatives and their use in the treatment of disease
6-(4-chlorophenyl)-5-(3,7-dimethyl-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)-N,1-dimethyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrole-3-carboxamide	IC50	15 nM	US-9550796: Pyrrolopyrrolone derivatives and their use as BET inhibitors
Ethyl (6-(4-chlorophenyl)-5-(3,7-dimethyl-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)-1-methyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrol-3-yl)carbamate	IC50	15 nM	US-9550796: Pyrrolopyrrolone derivatives and their use as BET inhibitors
(6R)-6-(4-chlorophenyl)-5-(1,5-dimethyl-6-oxo-3-pyridinyl)-3-ethyl-2-(2-methoxy-3-pyridinyl)-6H-pyrrolo[3,4-d]imidazol-4-one	IC50	15.5 nM	US-9890166: Imidazopyrrolidine derivatives and their use in the treatment of disease
4-(4-chloro-2-fluorophenyl)-5-(1,5-dimethyl-6-oxo-3-pyridinyl)-1-ethyl-3-methyl-4H-pyrrolo[3,4-d]pyrazol-6-one	IC50	16 nM	US-8975417: Pyrazolopyrrolidine derivatives and their use in the treatment of disease
(4R)-4-(4-chlorophenyl)-1-cyclopropyl-5-(3,8-dimethyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-3-(hydroxymethyl)-4H-pyrrolo[3,4-d]pyrazol-6-one	IC50	16 nM	US-8975417: Pyrazolopyrrolidine derivatives and their use in the treatment of disease
6-(4-chlorophenyl)-5-(3,8-dimethyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-N,1-dimethyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrole-3-carboxamide	IC50	16 nM	US-9550796: Pyrrolopyrrolone derivatives and their use as BET inhibitors
6-(4-chlorophenyl)-3-cyclopropyl-5-[3-(fluoromethyl)-8-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl]-1-methyl-6H-pyrrolo[3,4-d]pyrazol-4-one	IC50	16 nM	US-9624247: Pyrazolo-pyrrolidin-4-one derivatives as bet inhibitors and their use in the treatment of disease
(R)-6-(4-chlorophenyl)-5-(3,7-dimethyl-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)-1-isopropyl-2-(2-methoxypyridin-3-yl)-5,6-dihydropyrrolo[3,4-d]imidazol-4(1H)-one	IC50	16 nM	US-9890166: Imidazopyrrolidine derivatives and their use in the treatment of disease
(R)-6-(4-chlorophenyl)-5-(3-(difluoromethyl)-8-methyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-2-(2,4-dimethoxypyrimidin-5-yl)-1-isopropyl-5,6-dihydropyrrolo[3,4-d]imidazol-4(1H)-one	IC50	16 nM	US-9890166: Imidazopyrrolidine derivatives and their use in the treatment of disease
(4R)-5-(5-chloro-1-methyl-6-oxo-3-pyridinyl)-4-(4-chlorophenyl)-1-cyclopropyl-3-methyl-4H-pyrrolo[3,4-d]pyrazol-6-one	IC50	17 nM	US-8975417: Pyrazolopyrrolidine derivatives and their use in the treatment of disease
(4S)-4-(4-chlorophenyl)-5-(3,8-dimethyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-3-methyl-1,2,3,3a,4,6a-hexahydropyrrolo[3,4-c]pyrazol-6-one	IC50	17 nM	US-8975417: Pyrazolopyrrolidine derivatives and their use in the treatment of disease
6-(4-chlorophenyl)-5-(3,8-dimethyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-2-(1-methyl-2-oxo-1,2-dihydropyridin-3-yl)-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one	IC50	17 nM	US-9550796: Pyrrolopyrrolone derivatives and their use as BET inhibitors

ChEMBL bioactivities

1376 potent at pChembl≥5 of 1478 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.00	IC50	0.1	nM	CHEMBL5440537
10.00	IC50	0.1	nM	CHEMBL5440963
10.00	IC50	0.1	nM	CHEMBL5424952
10.00	IC50	0.1	nM	CHEMBL5432745
9.70	IC50	0.2	nM	CHEMBL4859923
9.70	IC50	0.2	nM	CHEMBL5401253
9.57	Ki	0.27	nM	CHEMBL4228445
9.57	Kd	0.27	nM	CHEMBL4648912
9.52	IC50	0.3	nM	CHEMBL5436475
9.52	IC50	0.3	nM	CHEMBL5422881
9.32	Ki	0.48	nM	CHEMBL4208129
9.24	Kd	0.57	nM	CHEMBL4648912
9.23	Kd	0.59	nM	CHEMBL3926851
9.22	Kd	0.6	nM	CHEMBL4173488
9.11	Kd	0.77	nM	CHEMBL4648912
9.10	IC50	0.8	nM	ABBV-744
9.05	Kd	0.9	nM	CHEMBL4171228
9.05	Ki	0.9	nM	CHEMBL4228445
9.04	IC50	0.92	nM	ABBV-744
9.00	Ki	1	nM	MIVEBRESIB
9.00	IC50	1	nM	CHEMBL5432745
9.00	IC50	1	nM	CHEMBL5422163
8.96	Kd	1.1	nM	CHEMBL4173488
8.96	Kd	1.1	nM	CHEMBL4171228
8.96	Kd	1.1	nM	CHEMBL3926851
8.96	EC50	1.1	nM	CHEMBL5266174
8.92	Kd	1.2	nM	CHEMBL4528047
8.89	Kd	1.3	nM	CHEMBL4440098
8.85	IC50	1.4	nM	EZOBRESIB
8.80	Kd	1.6	nM	CHEMBL5273240
8.77	Ki	1.7	nM	CHEMBL4555209
8.77	IC50	1.7	nM	CHEMBL5087175
8.77	Ki	1.7	nM	CHEMBL4164015
8.73	IC50	1.84	nM	CHEMBL4159382
8.70	IC50	2	nM	CHEMBL5400310
8.70	IC50	2	nM	CHEMBL5439607
8.66	Ki	2.2	nM	CHEMBL5752076
8.60	Ki	2.5	nM	CHEMBL4217457
8.60	Kd	2.5	nM	CHEMBL3926851
8.60	IC50	2.512	nM	CHEMBL4869149
8.59	Ki	2.6	nM	CHEMBL4215988
8.59	Ki	2.6	nM	CHEMBL5893845
8.58	IC50	2.63	nM	CHEMBL1995703
8.57	Ki	2.7	nM	CHEMBL4164015
8.54	IC50	2.9	nM	ABBV-744
8.54	Ki	2.9	nM	CHEMBL5893845
8.52	IC50	3	nM	CHEMBL4162832
8.52	IC50	3	nM	CHEMBL4780530
8.52	IC50	3	nM	CHEMBL5440537
8.52	IC50	3	nM	CHEMBL5424952

PubChem BioAssay actives

627 with measured affinity, of 1429 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
methyl 2-[(9S)-7-(4-chlorophenyl)-4-[2-[2-[[2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetyl]amino]ethoxy]ethylcarbamoyl]-5,13-dimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetate	1802215: Bromodomains Assay for DiscoveRx Gene Symbol from Article 10.1038/nchembio.2209: “Design and characterization of bivalent BET inhibitors.”	ki	<0.0001	uM
2-[7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]-N-[2-[2-[2-[2-[2-[2-[2-[2-[[2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetyl]amino]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethoxy]ethyl]acetamide	1802215: Bromodomains Assay for DiscoveRx Gene Symbol from Article 10.1038/nchembio.2209: “Design and characterization of bivalent BET inhibitors.”	ki	<0.0001	uM
2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]-N-(1,3,4-thiadiazol-2-yl)acetamide	1995878: Inhibition of BRD2 BD2 (unknown origin) by TR-FRET assay	ic50	0.0001	uM
methyl 2-[[2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetyl]amino]acetate	1995878: Inhibition of BRD2 BD2 (unknown origin) by TR-FRET assay	ic50	0.0001	uM
2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]-N-(1,2-oxazol-3-ylmethyl)acetamide	1995878: Inhibition of BRD2 BD2 (unknown origin) by TR-FRET assay	ic50	0.0001	uM
2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]-N-(1,3-oxazol-2-ylmethyl)acetamide	1995878: Inhibition of BRD2 BD2 (unknown origin) by TR-FRET assay	ic50	0.0001	uM
2-[8-fluoro-3-[3-methyl-5-(trideuteriomethyl)triazol-4-yl]-5-[(S)-oxan-4-yl(phenyl)methyl]pyrido[3,2-b]indol-7-yl]propan-2-ol	1870415: Inhibition of BRD2 (unknown origin)	ic50	0.0002	uM
N-benzyl-2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetamide	1995878: Inhibition of BRD2 BD2 (unknown origin) by TR-FRET assay	ic50	0.0002	uM
4-[(3-cyclopropyl-1-ethylpyrazol-5-yl)amino]-7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-N-methyl-9H-pyrimido[4,5-b]indole-2-carboxamide	1387714: Inhibition of FAM-labeled ZBA248 binding to recombinant N-terminal His6-tagged BRD2 bromodomain 2 (349 to 460 residues) (unknown origin) expressed in Escherichia coli Rosetta2 DE3 after 30 mins by fluorescence polarization assay	ki	0.0003	uM
N-[1-(1,1-dipyridin-2-ylethyl)-6-(1-methyl-7-oxo-6H-pyrrolo[2,3-c]pyridin-3-yl)indol-4-yl]ethanesulfonamide	1652233: Binding affinity to human partial length BRD2 bromodomain 1 isoform 1(K71 to N194 residues) expressed in bacterial expression system by BROMOscan assay	kd	0.0003	uM
2-[[2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetyl]amino]acetic acid	1995878: Inhibition of BRD2 BD2 (unknown origin) by TR-FRET assay	ic50	0.0003	uM
2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]-N-(pyridin-2-ylmethyl)acetamide	1995878: Inhibition of BRD2 BD2 (unknown origin) by TR-FRET assay	ic50	0.0003	uM
15-methyl-4-(methylsulfonylmethyl)-8-pyridin-2-yl-8,12,15-triazatetracyclo[8.6.1.02,7.013,17]heptadeca-1(16),2(7),3,5,10,13(17)-hexaen-14-one	1380472: Binding affinity to BRD2 bromodomain 1 to 2 (G73 to A560 amino acids) (unknown origin) using Alexa647-labeled BET-inhibitor as fluorescent probe by bromodomain TR-FRET binding assay	ki	0.0005	uM
N-(3-cyclopropyl-1-methylpyrazol-5-yl)-7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-2-methyl-9H-pyrimido[4,5-b]indol-4-amine	1356118: Binding affinity to human BRD2 bromodomain 2 (E348 to D455 residues) expressed in bacterial expression system by BROMOscan assay	kd	0.0006	uM
4-[2-cyclopropyl-7-(6-methylquinolin-5-yl)-3H-benzimidazol-5-yl]-3,5-dimethyl-1,2-oxazole	1535660: Binding affinity to human partial length BRD2 bromodomain 2 isoform 1 (E348 to D455 residues) expressed in bacterial expression system after 1 hr by bromoscan assay	kd	0.0006	uM
N-ethyl-4-[2-(4-fluoro-2,6-dimethylphenoxy)-5-(2-hydroxypropan-2-yl)phenyl]-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridine-2-carboxamide	2097971: Inhibition of BRD2 BD2 (unknown origin) using biotinylated tetra-acetylated H4 peptide SGRG-K(Ac)-GG-K(Ac)-GLG-K(Ac)-GGA-K(Ac)-RHRK-Biotin as substrate incubated for 1 hr by TR-FRET assay	ic50	0.0008	uM
4-(6-methoxy-2-methyl-4-quinolin-4-yl-9H-pyrimido[4,5-b]indol-7-yl)-3,5-dimethyl-1,2-oxazole	1371267: Binding affinity to human partial length BRD2 bromodomain 2 isoform 1 (349 to 460 residues) expressed in bacterial expression system by BROMOscan assay	kd	0.0009	uM
(2S,4R)-1-[(2S)-2-[[2-[3-[2-[[2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetyl]amino]ethoxy]propoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[(1S)-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]ethyl]pyrrolidine-2-carboxamide	1939893: Protac activity at BRD2/VHL-bound E3 ligase in human 22Rv1 cells assessed as reduction c-Myc level incubated for 24 hrs by Western blot analysis	ic50	0.0010	uM
2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]-N-(2H-triazol-4-ylmethyl)acetamide	1995878: Inhibition of BRD2 BD2 (unknown origin) by TR-FRET assay	ic50	0.0010	uM
N-[4-(2,4-difluorophenoxy)-3-(6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl)phenyl]ethanesulfonamide	1465486: Binding affinity to BRD2 BD1 to BD2 (G73 to A560 residues) (unknown origin)	ki	0.0010	uM
(2R,4S)-1-[(2R)-2-[[2-[3-[2-[2-[2-[[2-[(9R)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetyl]amino]ethoxy]ethoxy]ethoxy]-2-[2-[2-[2-[[2-[(9R)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetyl]amino]ethoxy]ethoxy]ethoxymethyl]-2-methylpropoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide	1946239: Protac activity at VHL/BRD2 in HEK293 cells assessed as degradation of BRD2 incubated for 4 hrs by Western blot analysis	ec50	0.0011	uM
(6R)-N-(4-chlorophenyl)-1-methyl-8-(1-methylpyrazol-4-yl)-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepin-6-amine	1565552: Binding affinity to human partial length BRD2 BD2 isoform 1 (E348 to D455 residues) expressed in bacterial expression system by bromoscan assay	kd	0.0012	uM
6-[2-(2,4-difluorophenoxy)-5-(ethylsulfonylmethyl)-3-pyridinyl]-8-methyl-2H-pyrrolo[1,2-a]pyrazin-1-one	1605884: Binding affinity to human partial length BRD2 BD2 isoform 1 (E348 to D455 residues) expressed in bacterial expression system by bromoscan assay	kd	0.0013	uM
2-[3-(3,5-dimethyltriazol-4-yl)-5-[(S)-oxan-4-yl(phenyl)methyl]pyrido[3,2-b]indol-7-yl]propan-2-ol	1830335: Inhibition of human BRD2 measured by TR-FRET assay	ic50	0.0014	uM
4-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-1-[(1R)-1-pyridin-2-ylethyl]pyrrolo[3,2-b]pyridin-3-yl]benzoic acid	1929263: Binding affinity to BRD2 BD1 (unknown origin) by BROMOscan assay	kd	0.0016	uM
2-[3-(3,5-dimethyl-1,2-oxazol-4-yl)-5-[(S)-oxan-4-yl(phenyl)methyl]pyrido[3,2-b]indol-7-yl]propan-2-ol	1830335: Inhibition of human BRD2 measured by TR-FRET assay	ic50	0.0017	uM
5-benzyl-13-methyl-4-[2-(1-methylpyrazol-4-yl)ethynyl]-8-oxa-3-thia-1,11,12-triazatricyclo[8.3.0.02,6]trideca-2(6),4,10,12-tetraene	1584508: Binding affinity to human BRD2 BD1 (72 to 205 residues) by fluorescence polarization assay	ki	0.0017	uM
2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]-N-(1,3-thiazol-2-yl)acetamide	1995878: Inhibition of BRD2 BD2 (unknown origin) by TR-FRET assay	ic50	0.0020	uM
2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]-N-(2-hydroxyethyl)acetamide	1995878: Inhibition of BRD2 BD2 (unknown origin) by TR-FRET assay	ic50	0.0020	uM
(3S)-5-N-[(1R,5S)-3-hydroxy-6-bicyclo[3.1.0]hexanyl]-7-N,3-dimethyl-3-phenyl-2H-1-benzofuran-5,7-dicarboxamide	1777125: Inhibition of recombinant human BRD2 BD2 (348 to 455 residues) expressed in bacterial expression system by bromoscan assay	ic50	0.0025	uM
8-(2,4-difluorophenyl)-15-methyl-4-(methylsulfonylmethyl)-8,12,15-triazatetracyclo[8.6.1.02,7.013,17]heptadeca-1(16),2(7),3,5,10,13(17)-hexaen-14-one	1380472: Binding affinity to BRD2 bromodomain 1 to 2 (G73 to A560 amino acids) (unknown origin) using Alexa647-labeled BET-inhibitor as fluorescent probe by bromodomain TR-FRET binding assay	ki	0.0025	uM
8-(4-fluorophenyl)-12-methyl-4-(methylsulfonylmethyl)-8,12,15-triazatetracyclo[8.6.1.02,7.013,17]heptadeca-1(16),2(7),3,5,10,13(17)-hexaen-14-one	1380472: Binding affinity to BRD2 bromodomain 1 to 2 (G73 to A560 amino acids) (unknown origin) using Alexa647-labeled BET-inhibitor as fluorescent probe by bromodomain TR-FRET binding assay	ki	0.0026	uM
7-(4-chlorophenyl)-1-methyl-N-[(1S)-1-phenylethyl]-5,6-dihydrotriazolo[1,5-d][1,4]benzodiazepine-9-carboxamide	1349398: Inhibition of human His-tagged Brd2 bromodomain 2 expressed in Escherichia coli BL21 (DE3) preincubated for 30 mins followed by addition of biotinylated acetyl-histone H4 peptide and measured after 1 hr by AlphaScreen assay	ic50	0.0030	uM
2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]-N-[(1-methylimidazol-4-yl)methyl]acetamide	1995878: Inhibition of BRD2 BD2 (unknown origin) by TR-FRET assay	ic50	0.0030	uM
5-[(4R)-6-(4-chlorophenyl)-1,4-dimethyl-4,5-dihydro-[1,2,4]triazolo[3,4-d][1,5]benzodiazepin-8-yl]pyridin-2-amine	1711611: Inhibition of BRD2 BD1 (unknown origin) using biotinylated JQ1 analog as substrate measured after 20 mins by AlphaLISA assay	ic50	0.0030	uM
2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]-N-(4-hydroxyphenyl)acetamide	1995878: Inhibition of BRD2 BD2 (unknown origin) by TR-FRET assay	ic50	0.0030	uM
1,3-dimethyl-5-[1-[[(3S)-1-(1-propan-2-ylpiperidine-4-carbonyl)piperidin-3-yl]methyl]benzimidazol-2-yl]pyridin-2-one	2022140: Inhibition of BRD2 BD1 (unknown origin) by BROMOscan assay	kd	0.0032	uM
4-[(2S,4R)-1-acetyl-4-(4-chloroanilino)-2-methyl-3,4-dihydro-2H-quinolin-6-yl]benzoic acid	1165969: Inhibition of human BRD2 bromodomain 2 by BROMOscan assay	ic50	0.0032	uM
tert-butyl 2-[(9S)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetate	1905950: Inhibition of C-terminal His6-tagged BRD2 BD2 (unknown origin) using H-YSGRGK(Ac)GGK(Ac)GLGK(Ac)-GGAK(Ac)RHRK-Biotin-OH as substrate incubated for 1 hrs by HTRF assay	ic50	0.0039	uM
7-(4-chlorophenyl)-N-[(1S)-1-(4-fluorophenyl)ethyl]-1-methyl-5,6-dihydrotriazolo[1,5-d][1,4]benzodiazepine-9-carboxamide	1349398: Inhibition of human His-tagged Brd2 bromodomain 2 expressed in Escherichia coli BL21 (DE3) preincubated for 30 mins followed by addition of biotinylated acetyl-histone H4 peptide and measured after 1 hr by AlphaScreen assay	ic50	0.0040	uM
(3R,4R)-N-cyclohexyl-4-[[5-(furan-2-yl)-3-methyl-2-oxo-1H-1,7-naphthyridin-8-yl]amino]-1-methylpiperidine-3-carboxamide	1721393: Binding affinity to full length BRD2 BD1 in human HuT78 cell lysates incubated for 45 mins by liquid chromatography-mass spectrometry based chemoproteomic binding assay	kd	0.0040	uM
2-(2-cyclopentyl-1H-imidazol-5-yl)-7-[2-(4-fluoro-2,6-dimethylphenoxy)-5-(2-hydroxypropan-2-yl)phenyl]-5-methylfuro[3,2-c]pyridin-4-one	1905950: Inhibition of C-terminal His6-tagged BRD2 BD2 (unknown origin) using H-YSGRGK(Ac)GGK(Ac)GLGK(Ac)-GGAK(Ac)RHRK-Biotin-OH as substrate incubated for 1 hrs by HTRF assay	ic50	0.0051	uM
N-[4-[(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxalin-4-yl)amino]butyl]-3-methylbutanamide	2100764: Binding affinity to human BRD2 assessed as dissociation constant by ITC analysis	kd	0.0056	uM
tert-butyl 2-[(9R)-7-(4-chlorophenyl)-4,5,13-trimethyl-3-thia-1,8,11,12-tetrazatricyclo[8.3.0.02,6]trideca-2(6),4,7,10,12-pentaen-9-yl]acetate	1802215: Bromodomains Assay for DiscoveRx Gene Symbol from Article 10.1038/nchembio.2209: “Design and characterization of bivalent BET inhibitors.”	kd	0.0056	uM
3-[(11-methyl-12-oxo-2,11-diazatetracyclo[8.6.1.03,8.013,17]heptadeca-1(16),3,5,7,9,13(17),14-heptaen-2-yl)methyl]-N-(1-methylpiperidin-4-yl)benzamide	1998774: Inhibition of N-terminal his-tagged human recombinant BRD2 BD2 (2 to 473 residues) expressed in Escherichia coli by AlphaScreen assay	ic50	0.0059	uM
7-(4-chlorophenyl)-1-methyl-9-(2H-tetrazol-5-yl)-5,6-dihydrotriazolo[1,5-d][1,4]benzodiazepine	1349397: Inhibition of human His-tagged Brd2 bromodomain 1 expressed in Escherichia coli BL21 (DE3) preincubated for 30 mins followed by addition of biotinylated acetyl-histone H4 peptide and measured after 1 hr by AlphaScreen assay	ic50	0.0060	uM
4-[[(2S,4R)-1-acetyl-2-methyl-6-(1H-pyrazol-5-yl)-3,4-dihydro-2H-quinolin-4-yl]amino]benzonitrile	1939297: Binding affinity to BDR2- BD2 (unknown origin) by TR-FRET assay	kd	0.0060	uM
7-[2-(cyclopropylmethoxy)phenyl]-5-methyl-2-[[(2R)-2-methyl-4-methylsulfonylpiperazin-1-yl]methyl]furo[3,2-c]pyridin-4-one	2112651: Binding affinity to BRD2 BD1 (unknown origin) assessed as dissociation constant by BROMOscan assay	kd	0.0065	uM
5-methyl-2-[[(2R)-2-methyl-4-methylsulfonylpiperazin-1-yl]methyl]-7-[3-(methylsulfonylmethyl)phenyl]furo[3,2-c]pyridin-4-one	2112651: Binding affinity to BRD2 BD1 (unknown origin) assessed as dissociation constant by BROMOscan assay	kd	0.0074	uM
(2S,4R)-1-acetyl-4-[(5-chloropyrimidin-2-yl)amino]-2-methyl-3,4-dihydro-2H-quinoline-6-carboxamide	1900664: Binding affinity to BRD2 BD2 (unknown origin) assessed as dissociation constant	kd	0.0079	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	affects binding, decreases reaction, decreases expression, increases expression	6
Acetaminophen	increases expression	4
bisphenol A	affects expression, affects cotreatment, increases methylation, increases expression	3
Cisplatin	decreases expression, increases expression	3
Oxygen	decreases expression, increases expression	2
Tobacco Smoke Pollution	increases expression	2
Cyclosporine	increases expression	2
aristolochic acid I	increases expression	1
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	decreases expression	1
OTX015	increases expression	1
FR900359	affects phosphorylation	1
testosterone enanthate	affects expression	1
chloroacetaldehyde	affects expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
2-methyl-4-isothiazolin-3-one	increases expression	1
3,3’-diindolylmethane	decreases reaction, increases expression	1
afimoxifene	decreases response to substance	1
sodium arsenite	increases expression	1
cobaltous chloride	increases expression	1
periodate-oxidized adenosine	affects expression	1
ferrous chloride	increases expression	1
nickel sulfate	decreases expression	1
coumarin	increases phosphorylation	1
methacrylaldehyde	affects cotreatment, decreases expression, increases oxidation, increases abundance	1
diethyl malate	increases expression	1
di-n-butylphosphoric acid	affects expression	1
azoxystrobin	increases expression	1
CGP 52608	increases reaction, affects binding	1

ChEMBL screening assays

681 unique, capped per target: 655 binding, 19 functional, 7 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1832991	Binding	Binding affinity to second bromodomain of BRD2 assessed as change in melting temperature at 100 uM by differential scanning fluorimetry	3,5-dimethylisoxazoles act as acetyl-lysine-mimetic bromodomain ligands. — J Med Chem
CHEMBL4182255	ADMET	Inhibition of recombinant human BRD2 bromodomain 1 (49 to 170 residues) using biotin labeled peptide substrate preincubated for 15 mins followed by substrate addition measured after 1 hr by TR-FRET assay	Exploiting a water network to achieve enthalpy-driven, bromodomain-selective BET inhibitors. — Bioorg Med Chem
CHEMBL5210058	Functional	Affinity Phenotypic Cellular interaction (Cell Proliferation (Cell TiterGlo assay Promega in NMC 11060 cells)) EUB0000330a BRD2	Affinity Phenotypic Cellular Literature for EUbOPEN Chemogenomics Library wave 3

Cellosaurus cell lines

9 cell lines: 6 cancer cell line, 3 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2SZ	Abcam HEK293T BRD2 KO	Transformed cell line	Female
CVCL_B7W8	Abcam Raji BRD2 KO	Cancer cell line	Male
CVCL_B9WR	Abcam THP-1 BRD2 KO	Cancer cell line	Male
CVCL_C6YS	Abcam PC-3 BRD2 KO	Cancer cell line	Male
CVCL_KW02	InCELL Hunter HEK 293 BRD2(1) Bromodomain	Transformed cell line	Female
CVCL_KW03	InCELL Hunter HEK 293 BRD2(1,2) Bromodomain	Transformed cell line	Female
CVCL_SF53	HAP1 BRD2 (-) 1	Cancer cell line	Male
CVCL_SF54	HAP1 BRD2 (-) 2	Cancer cell line	Male
CVCL_SF55	HAP1 BRD2 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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