BRD3

Summary

BRD3 (bromodomain containing 3, HGNC:1104) is a protein-coding gene on chromosome 9q34.2, encoding Bromodomain-containing protein 3 (Q15059). Chromatin reader that recognizes and binds acetylated histones, thereby controlling gene expression and remodeling chromatin structures.

This gene was identified based on its homology to the gene encoding the RING3 protein, a serine/threonine kinase. The gene localizes to 9q34, a region which contains several major histocompatibility complex (MHC) genes. The function of the encoded protein is not known.

Source: NCBI Gene 8019 — RefSeq curated summary.

At a glance

• GWAS associations: 38
• Clinical variants (ClinVar): 105 total
• Druggable target: yes — 8 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_007371

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:1104
Approved symbol	BRD3
Name	bromodomain containing 3
Location	9q34.2
Locus type	gene with protein product
Status	Approved
Aliases	RING3L, ORFX, KIAA0043, FSHRG2
Ensembl gene	ENSG00000169925
Ensembl biotype	protein_coding
OMIM	601541
Entrez	8019

Gene structure

Transcript identifiers

Ensembl transcripts: 16 — 14 protein_coding, 1 protein_coding_CDS_not_defined, 1 retained_intron

ENST00000303407, ENST00000371834, ENST00000371842, ENST00000433041, ENST00000473349, ENST00000494743, ENST00000883997, ENST00000883998, ENST00000883999, ENST00000884000, ENST00000884001, ENST00000884002, ENST00000933194, ENST00000933195, ENST00000933196, ENST00000933197

RefSeq mRNA: 1 — MANE Select: NM_007371 NM_007371

CCDS: CCDS6980

Canonical transcript exons

ENST00000303407 — 12 exons

Exon	Start	End
ENSE00001129684	134040034	134040269
ENSE00001129727	134030305	134033705
ENSE00001616318	134051562	134051709
ENSE00001628171	134050374	134050588
ENSE00001633127	134041760	134041951
ENSE00001739092	134045293	134045421
ENSE00001798041	134067945	134068026
ENSE00002355355	134048083	134048454
ENSE00002402054	134052306	134052443
ENSE00002693824	134053265	134053590
ENSE00003565115	134034701	134034829
ENSE00003585595	134036032	134036324

Expression profiles

Bgee: expression breadth ubiquitous, 302 present calls, max score 96.30.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.0473 / max 922.6606, expressed in 1797 samples.

FANTOM5 promoters (6 alternative TSS)

Promoter ID	TPM avg	Samples expressed
103044	6.8388	1600
103046	6.5259	1638
103047	6.1192	1688
103048	1.9156	1198
103049	1.6361	855
103045	0.0117	3

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
nipple	UBERON:0002030	96.30	gold quality
medial globus pallidus	UBERON:0002477	96.07	gold quality
globus pallidus	UBERON:0001875	95.75	gold quality
cranial nerve II	UBERON:0000941	95.30	gold quality
cortical plate	UBERON:0005343	95.18	gold quality
oocyte	CL:0000023	95.04	gold quality
inferior vagus X ganglion	UBERON:0005363	94.85	gold quality
pylorus	UBERON:0001166	94.71	gold quality
secondary oocyte	CL:0000655	94.53	gold quality
ventral tegmental area	UBERON:0002691	94.45	gold quality
endometrium epithelium	UBERON:0004811	94.22	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	94.07	gold quality
lateral globus pallidus	UBERON:0002476	94.01	gold quality
ganglionic eminence	UBERON:0004023	93.98	gold quality
cardia of stomach	UBERON:0001162	93.95	gold quality
pericardium	UBERON:0002407	93.90	gold quality
renal medulla	UBERON:0000362	93.80	gold quality
embryo	UBERON:0000922	93.69	gold quality
inferior olivary complex	UBERON:0002127	93.63	gold quality
medulla oblongata	UBERON:0001896	93.45	gold quality
mammary duct	UBERON:0001765	93.36	gold quality
subthalamic nucleus	UBERON:0001906	93.11	gold quality
paraflocculus	UBERON:0005351	93.10	gold quality
saphenous vein	UBERON:0007318	93.10	gold quality
epithelium of mammary gland	UBERON:0003244	93.06	gold quality
trigeminal ganglion	UBERON:0001675	92.94	gold quality
upper leg skin	UBERON:0004262	92.84	gold quality
cerebellar vermis	UBERON:0004720	92.57	gold quality
cartilage tissue	UBERON:0002418	92.52	gold quality
trabecular bone tissue	UBERON:0002483	92.31	gold quality

Single-cell (SCXA)

Detected in 2 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	9.15
E-GEOD-93593	no	6.51

Regulation

Is transcription factor: no

Upstream regulators (CollecTRI, top): BRD7

miRNA regulators (miRDB)

162 targeting BRD3, 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-8485	100.00	77.57	4731
HSA-MIR-4795-3P	100.00	74.62	4024
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-126-5P	100.00	72.71	3180
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-3925-3P	100.00	69.95	1237
HSA-MIR-4500	99.99	72.72	2367
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-12136	99.98	72.81	5713
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-4789-5P	99.98	70.76	2721
HSA-LET-7A-5P	99.98	72.29	1790
HSA-LET-7B-5P	99.98	72.31	1790
HSA-LET-7C-5P	99.98	72.29	1790
HSA-LET-7E-5P	99.98	72.29	1790
HSA-LET-7F-5P	99.98	72.56	1784
HSA-LET-7G-5P	99.98	72.37	1784

Literature-anchored findings (GeneRIF, showing 24)

• Activated lymphocytes induced by mitogens or antigens express various sets of genes, including those involved in the expression of cytokines, surface molecules, and nuclear proteins. (PMID:12371535)
• BRD-NUT fusion proteins contribute to carcinogenesis by associating with chromatin and interfering with epithelial differentiation. (PMID:17934517)
• 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)
• the structural basis for GATA1 and Brd3 interaction was described. (PMID:21555453)
• 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)
• BRD2, BRD3, and BRD4 interact with gammaretroviral INs and serve as cofactors for murine leukemia virus integration. (PMID:24049186)
• Here, we identify NCT, a complex comprising the Nrc1 BET-family tandem bromodomain protein (SPAC631.02), casein kinase II (CKII), and several TAFs, as a regulator of condensin function. (PMID:24565511)
• Ewing sarcoma may be susceptible to treatment with epigenetic inhibitors blocking BRD3/4 activity and the associated pathognomonic EWS-FLT1 transcriptional program. (PMID:26623725)
• An isoform of BRD3, BRD3R (BRD3 with Reprogramming activity) is a reprogramming factor. (PMID:26947130)
• 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)
• conclude that BRD3/4 and the FLT3-TAK1/NF-kB pathways collectively control a set of targets that are critically important for the survival of human MLL-AF9 cells (PMID:29240787)
• Results provide evidence that both BRD3 and BRD4 are repressors of epithelial-to-mesenchymal transition in breast cancer cells. (PMID:29437854)
• data provide insight into the mechanisms by which BET family proteins might link chromatin acetylation to transcriptional outcomes and uncover an unexpected functional similarity between BET and YEATS family proteins (PMID:29567837)
• Recruitment of Brd3 (and Brd4) to chromatin is essential for inflammation mediator-induced matrix-degrading enzyme expression. (PMID:30786900)
• This study presents the first co-crystal structure of SPOP and a bromodomain containing protein (BRD3). (PMID:31026449)
• The BET proteins Brd3 and Brd4 were shown to bind to the NOX4 promoter and drive TGF-beta-induced NOX4 expression. Our data indicate a critical role of BET proteins in promoting redox imbalance and pulmonary myofibroblast activation and support BET bromodomain inhibitors as a potential therapy for fibrotic lung disease. (PMID:31119153)
• BRD3 is recruited to and controls the activity of a subset ERa transcriptional enhancers, providing a therapeutic opportunity to target BRD3 with BET inhibitors in ERa-positive breast cancers. (PMID:31551256)
• Comparative structure-function analysis of bromodomain and extraterminal motif (BET) proteins in a gene-complementation system. (PMID:31792058)
• BCL6 confers KRAS-mutant non-small-cell lung cancer resistance to BET inhibitors. (PMID:33393503)
• A common binding motif in the ET domain of BRD3 forms polymorphic structural interfaces with host and viral proteins. (PMID:33592170)
• Epigenetic readers and lung cancer: the rs2427964C>T variant of the bromodomain and extraterminal domain gene BRD3 is associated with poorer survival outcome in NSCLC. (PMID:34605158)
• Kinome-wide screening uncovers a role for Bromodomain Protein 3 in DNA double-stranded break repair. (PMID:36608404)
• Targeting BRD3 eradicates nuclear TYRO3-induced colorectal cancer metastasis. (PMID:37043564)
• Tumor suppressive role of the epigenetic master regulator BRD3 in colorectal cancer. (PMID:38494600)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Brd3	ENSMUSG00000026918
rattus_norvegicus	Brd3	ENSRNOG00000007681
drosophila_melanogaster	tbrd-1	FBGN0039124

Paralogs (11): BAZ1B (ENSG00000009954), BAZ2A (ENSG00000076108), CECR2 (ENSG00000099954), KAT2A (ENSG00000108773), KAT2B (ENSG00000114166), BAZ2B (ENSG00000123636), BRDT (ENSG00000137948), BRD4 (ENSG00000141867), BPTF (ENSG00000171634), BAZ1A (ENSG00000198604), BRD2 (ENSG00000204256)

Protein

Protein identifiers

Bromodomain-containing protein 3 — Q15059 (reviewed: Q15059)

Alternative names: RING3-like protein

All UniProt accessions (4): Q15059, A0A140F1N4, A9J571, A9J575

UniProt curated annotations — full annotation on UniProt →

Function. Chromatin reader that recognizes and binds acetylated histones, 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. In vitro, binds acetylated lysine residues on the N-terminus of histone H2A, H2B, H3 and H4. Involved in endoderm differentiation via its association with long non-coding RNA (lncRNA) DIGIT: BRD3 undergoes liquid-liquid phase separation upon binding to lncRNA DIGIT, promoting binding to histone H3 acetylated at ‘Lys-18’ (H3K18ac) to induce endoderm gene expression. Also binds non-histones acetylated proteins, such as GATA1 and GATA2: regulates transcription by promoting the binding of the transcription factor GATA1 to its targets.

Subunit / interactions. Interacts (via bromo domain 1) with GATA1 acetylated at ‘Lys-312’ and ‘Lys-315’. Interacts (via bromo domain 1) with GATA2 acetylated on lysine residues. Interacts (via NET domain) with CHD4 (via KIKL motif). Interacts (via NET domain) with SMARCA4 (via KIKL motif). Interacts (via NET domain) with NSD3 (via KIKL motif). (Microbial infection) Interacts with the Integrase protein of Moloney murine leukemia virus (MLV).

Subcellular location. Nucleus. Chromosome.

Tissue specificity. Ubiquitous.

Disease relevance. A chromosomal aberration involving BRD3 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;9)(q14;q34) with NUTM1 which produces a BRD3-NUTM1 fusion protein.

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 Bromo domains specifically recognize and bind acetylated histones. The NET domain recognizes and binds the ‘KIKL’ motif found in chromatin proteins.

Similarity. Belongs to the BET family.

Isoforms (2)

UniProt ID	Names	Canonical?
Q15059-1	1	yes
Q15059-2	2

RefSeq proteins (1): NP_031397* (*=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 (63 total): helix 21, region of interest 7, compositionally biased region 7, sequence variant 6, modified residue 4, turn 4, domain 3, strand 3, coiled-coil region 2, splice variant 2, initiator methionine 1, chain 1, site 1, cross-link 1

Structure

Experimental structures (PDB)

48 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
6QJU	X-RAY DIFFRACTION	1.2
3S92	X-RAY DIFFRACTION	1.36
9NN4	X-RAY DIFFRACTION	1.37
2NXB	X-RAY DIFFRACTION	1.4
7TOA	X-RAY DIFFRACTION	1.41
7LAY	X-RAY DIFFRACTION	1.45
8CV5	X-RAY DIFFRACTION	1.47
7L72	X-RAY DIFFRACTION	1.5
7RJL	X-RAY DIFFRACTION	1.5
7TO8	X-RAY DIFFRACTION	1.5
7L9L	X-RAY DIFFRACTION	1.55
7TO9	X-RAY DIFFRACTION	1.6
9MPN	X-RAY DIFFRACTION	1.6
2OO1	X-RAY DIFFRACTION	1.7
5HFR	X-RAY DIFFRACTION	1.7
7R8R	X-RAY DIFFRACTION	1.8
7UG5	X-RAY DIFFRACTION	1.8
6I5P	X-RAY DIFFRACTION	1.81
24OS	X-RAY DIFFRACTION	1.83
6I68	X-RAY DIFFRACTION	1.85
7RJK	X-RAY DIFFRACTION	1.85
6U4A	X-RAY DIFFRACTION	1.88
5A7C	X-RAY DIFFRACTION	1.9
6I41	X-RAY DIFFRACTION	1.9
8B5A	X-RAY DIFFRACTION	1.92
7TO7	X-RAY DIFFRACTION	1.93
7RJN	X-RAY DIFFRACTION	1.95
7LB4	X-RAY DIFFRACTION	2
3S91	X-RAY DIFFRACTION	2.06
7RJM	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q15059-F1	68.65	0.36

Functional residue map

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

Catalytic / active sites (1): 647–648 (breakpoint for translocation to form bdr3-nutm1 fusion protein)

Post-translational modifications (5): 2, 263, 281, 563, 414

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 195 (showing top): JI_RESPONSE_TO_FSH_UP, GOBP_FORMATION_OF_PRIMARY_GERM_LAYER, MORF_RAF1, MARTINEZ_RB1_TARGETS_DN, GOBP_PROTEIN_LOCALIZATION_TO_CHROMATIN, BLALOCK_ALZHEIMERS_DISEASE_UP, GROSS_HYPOXIA_VIA_ELK3_UP, GOBP_PROTEIN_LOCALIZATION_TO_CHROMOSOME, GROSS_HYPOXIA_VIA_ELK3_ONLY_DN, WTGAAAT_UNKNOWN, GOBP_GASTRULATION, GOBP_ENDODERM_DEVELOPMENT, CCCNNNNNNAAGWT_UNKNOWN, BOYAULT_LIVER_CANCER_SUBCLASS_G1_UP, CAIRO_HEPATOBLASTOMA_UP

GO Biological Process (7): chromatin remodeling (GO:0006338), regulation of transcription by RNA polymerase II (GO:0006357), endodermal cell differentiation (GO:0035987), positive regulation of transcription by RNA polymerase II (GO:0045944), protein localization to chromatin (GO:0071168), chromatin organization (GO:0006325), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (12): chromatin binding (GO:0003682), protein serine/threonine kinase activity (GO:0004674), histone binding (GO:0042393), histone H3K9me2/3 reader activity (GO:0062072), lncRNA binding (GO:0106222), histone H3K18cr reader activity (GO:0140017), histone H3K9cr reader activity (GO:0140019), histone H3K27cr reader activity (GO:0140038), histone reader activity (GO:0140566), molecular condensate scaffold activity (GO:0140693), protein binding (GO:0005515), protein-macromolecule adaptor activity (GO:0030674)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), chromosome (GO:0005694)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
histone H3 reader activity	4
transcription by RNA polymerase II	2
binding	2
protein binding	2
chromatin organization	1
regulation of DNA-templated transcription	1
endoderm formation	1
cell differentiation	1
regulation of transcription by RNA polymerase II	1
positive regulation of DNA-templated transcription	1
protein localization to chromosome	1
cellular component organization	1
DNA-templated transcription	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
protein kinase activity	1
RNA binding	1
nucleosome	1
histone binding	1
chromatin-protein adaptor activity	1
protein-macromolecule adaptor activity	1
molecular adaptor activity	1
chromosome	1
cellular anatomical structure	1
intracellular membrane-bounded organelle	1
intracellular membraneless organelle	1

Protein interactions and networks

STRING

2350 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BRD3	GATA1	P15976	986
BRD3	BRD2	P25440	952
BRD3	BRDT	Q58F21	913
BRD3	HLA-DMA	P28067	845
BRD3	HLA-DOA	P06340	825
BRD3	H4C16	P02304	806
BRD3	H4C7	Q99525	806
BRD3	NUTM1	Q86Y26	804
BRD3	NSD2	O96028	789
BRD3	BRD4	O60885	753
BRD3	ZNF532	Q9HCE3	751
BRD3	MYC	P01106	734
BRD3	DEFB1	P60022	706
BRD3	NSD3	Q9BZ95	679
BRD3	ZNF592	Q92610	657

IntAct

46 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
SUMO1	CBX4	psi-mi:“MI:0914”(association)	0.600
FAM90A1	RFPL4A	psi-mi:“MI:0914”(association)	0.530
PIP4K2A	AP3B1	psi-mi:“MI:0914”(association)	0.530
BAG2	HGS	psi-mi:“MI:0914”(association)	0.530
MYC	BRD3	psi-mi:“MI:0915”(physical association)	0.520
	BRD3	psi-mi:“MI:0407”(direct interaction)	0.440
SRPK2	BRD3	psi-mi:“MI:0217”(phosphorylation reaction)	0.440
H3C1	SMCHD1	psi-mi:“MI:2364”(proximity)	0.410
BRD3	RPL4	psi-mi:“MI:0915”(physical association)	0.400
BRD3	BRD2	psi-mi:“MI:0915”(physical association)	0.400
BRD3	MAP1LC3B	psi-mi:“MI:0915”(physical association)	0.370
Knl1	SPC24	psi-mi:“MI:0914”(association)	0.350
Nfyc	BDP1	psi-mi:“MI:0914”(association)	0.350
TACC1	TACC2	psi-mi:“MI:0914”(association)	0.350
Junb	RGPD3	psi-mi:“MI:0914”(association)	0.350
JUN		psi-mi:“MI:0914”(association)	0.350
	PLK4	psi-mi:“MI:0914”(association)	0.350
	TBKBP1	psi-mi:“MI:0914”(association)	0.350
	AHRR	psi-mi:“MI:0914”(association)	0.350
	AURKA	psi-mi:“MI:0914”(association)	0.350
ESR1	ESYT2	psi-mi:“MI:0914”(association)	0.350
SPDYE4	RPS10-NUDT3	psi-mi:“MI:0914”(association)	0.350
SPDYE7P	SPDYE3	psi-mi:“MI:0914”(association)	0.350
PIP4K2C	AP3B1	psi-mi:“MI:0914”(association)	0.350

BioGRID (644): BRD3 (Affinity Capture-MS), BRD3 (Affinity Capture-RNA), BRD3 (Affinity Capture-MS), BRD3 (Co-fractionation), BRD3 (Co-fractionation), BRD3 (Co-fractionation), BRD3 (Co-fractionation), RUVBL2 (Co-fractionation), BRD3 (Proximity Label-MS), BRD3 (Proximity Label-MS), BRD3 (Affinity Capture-MS), BRD3 (Affinity Capture-MS), BRD3 (Affinity Capture-MS), BRD3 (Affinity Capture-MS), BRD3 (Proximity Label-MS)

ESM2 similar proteins: A2AJK6, A4QNP0, D4A7T3, E1B7L7, F1MH24, F1QW93, F1R5H6, F1SPM8, O60885, O75175, O94842, O95104, P0C1X8, P25440, P61129, Q06A37, Q08D75, Q0P5K4, Q15059, Q2M2I8, Q32S26, Q3UHJ0, Q4R8Y1, Q58F21, Q5R6A9, Q5TJG6, Q5U4Q0, Q62901, Q63627, Q6DFF2, Q6DID3, Q6DJL0, Q6MGA9, Q6P4S6, Q6ZU65, Q7JJ13, Q7TSH6, Q7ZUK7, Q80TZ9, Q80WC1

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

6 interactions.

A	Effect	B	Mechanism
BRD7	“up-regulates quantity by expression”	BRD3	“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”	BRD3	“chemical inhibition”
“CID 132010322”	“down-regulates activity”	BRD3	“chemical inhibition”
BRD3	“up-regulates activity”	EP300	binding
JQ1	“down-regulates activity”	BRD3	“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”	BRD3	“chemical inhibition”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 59 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
ESR-mediated signaling	5	16.4×	3e-03
Regulation of PD-L1(CD274) transcription	5	13.9×	4e-03
PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling	5	12.4×	4e-03
Estrogen-dependent gene expression	5	9.7×	8e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	70
Likely benign	8
Benign	3

Top pathogenic / likely-pathogenic (0)

SpliceAI

2551 predictions. Top by Δscore:

Variant	Effect	Δscore
9:134034695:CGGTA:C	donor_loss	1.0000
9:134034696:GGTAC:G	donor_loss	1.0000
9:134034697:GTA:G	donor_loss	1.0000
9:134034698:TACCT:T	donor_loss	1.0000
9:134034700:C:A	donor_loss	1.0000
9:134034704:T:A	donor_gain	1.0000
9:134034825:TGCTG:T	acceptor_gain	1.0000
9:134034827:CTG:C	acceptor_gain	1.0000
9:134034830:C:CC	acceptor_gain	1.0000
9:134036030:A:AC	donor_gain	1.0000
9:134036031:C:CC	donor_gain	1.0000
9:134036031:CAGAA:C	donor_gain	1.0000
9:134036075:T:C	donor_gain	1.0000
9:134041755:CCCA:C	donor_loss	1.0000
9:134041757:CACCT:C	donor_loss	1.0000
9:134041758:A:C	donor_loss	1.0000
9:134041759:C:G	donor_loss	1.0000
9:134041759:CCTG:C	donor_gain	1.0000
9:134041948:CGTC:C	acceptor_gain	1.0000
9:134041951:CCTGC:C	acceptor_loss	1.0000
9:134041952:C:CG	acceptor_loss	1.0000
9:134041953:T:G	acceptor_loss	1.0000
9:134045422:C:CC	acceptor_gain	1.0000
9:134048079:GTA:G	donor_loss	1.0000
9:134048080:TAC:T	donor_loss	1.0000
9:134048081:A:AC	donor_gain	1.0000
9:134048082:C:A	donor_loss	1.0000
9:134048082:C:CT	donor_gain	1.0000
9:134048082:CTTT:C	donor_gain	1.0000
9:134048085:T:A	donor_gain	1.0000

AlphaMissense

4768 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:134036070:A:T	V633D	1.000
9:134036071:C:A	V633F	1.000
9:134036071:C:G	V633L	1.000
9:134036074:A:C	Y632D	1.000
9:134036082:A:C	L629R	1.000
9:134036082:A:G	L629P	1.000
9:134036082:A:T	L629Q	1.000
9:134036088:C:G	R627P	1.000
9:134036090:C:A	L626F	1.000
9:134036090:C:G	L626F	1.000
9:134036091:A:C	L626W	1.000
9:134036091:A:G	L626S	1.000
9:134036094:G:A	T625I	1.000
9:134036106:A:C	L621R	1.000
9:134036106:A:G	L621P	1.000
9:134036106:A:T	L621Q	1.000
9:134036111:C:A	E619D	1.000
9:134036111:C:G	E619D	1.000
9:134036112:T:A	E619V	1.000
9:134036112:T:C	E619G	1.000
9:134036112:T:G	E619A	1.000
9:134036113:C:T	E619K	1.000
9:134036114:A:C	F618L	1.000
9:134036114:A:T	F618L	1.000
9:134036115:A:C	F618C	1.000
9:134036115:A:G	F618S	1.000
9:134036116:A:C	F618V	1.000
9:134036116:A:G	F618L	1.000
9:134036116:A:T	F618I	1.000
9:134036117:G:C	D617E	1.000

dbSNP variants (sampled 300 via entrez): RS1000005512 (9:134054239 G>A,T), RS1000163096 (9:134030144 G>A), RS1000173492 (9:134045016 C>A), RS1000331273 (9:134040521 G>A,C), RS1000527141 (9:134052673 G>A), RS1000590834 (9:134048119 G>A), RS1000610769 (9:134046288 G>A,C), RS1000611447 (9:134049773 C>T), RS1000697760 (9:134043718 AG>A), RS1000787303 (9:134056848 G>A), RS1000872141 (9:134040701 T>A), RS1000916655 (9:134067920 G>A), RS1000958565 (9:134039102 G>A), RS1000968621 (9:134068258 G>GC), RS1000982860 (9:134067059 G>A,C)

Disease associations

OMIM: gene MIM:601541 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): primary ovarian failure (MONDO:0005387)

Orphanet (1): NON RARE IN EUROPE: Primary ovarian failure (Orphanet:619)

HPO phenotypes

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

GWAS associations

38 associations (top):

Study	Trait	p-value
GCST001337_29	Platelet count	2.000000e-10
GCST004599_2	Mean platelet volume	2.000000e-28
GCST004600_84	Eosinophil percentage of white cells	3.000000e-14
GCST004606_17	Eosinophil count	4.000000e-10
GCST004608_157	Granulocyte percentage of myeloid white cells	5.000000e-09
GCST004616_76	Platelet distribution width	4.000000e-13
GCST004617_175	Eosinophil percentage of granulocytes	9.000000e-16
GCST004620_27	Sum basophil neutrophil counts	4.000000e-09
GCST004621_9	Red cell distribution width	9.000000e-15
GCST004623_130	Neutrophil percentage of granulocytes	1.000000e-16
GCST004624_142	Sum eosinophil basophil counts	9.000000e-10
GCST004629_85	Neutrophil count	2.000000e-09
GCST004633_86	Neutrophil percentage of white cells	2.000000e-10
GCST004863_4	Mosquito bite size	4.000000e-07
GCST005580_1	Intraocular pressure	1.000000e-15
GCST005580_244	Intraocular pressure	4.000000e-16
GCST006366_5	Central corneal thickness	5.000000e-11
GCST006804_48	Red cell distribution width	1.000000e-13
GCST007002_4	Cerebrospinal fluid t-tau levels in normal cognition	6.000000e-07
GCST007328_81	Alcohol consumption (drinks per week)	1.000000e-08
GCST007998_28	Intraocular pressure	9.000000e-07
GCST008058_281	Estimated glomerular filtration rate	4.000000e-07
GCST008595_137	Cognitive ability, years of educational attainment or schizophrenia (pleiotropy)	3.000000e-08
GCST009414_28	Central corneal thickness	3.000000e-11
GCST010241_415	Apolipoprotein A1 levels	2.000000e-10
GCST010242_157	HDL cholesterol levels	7.000000e-12
GCST011378_2	Brain-derived neurotrophic factor levels	3.000000e-11
GCST90002382_282	Eosinophil percentage of white cells	3.000000e-27
GCST90002387_346	Immature fraction of reticulocytes	7.000000e-16
GCST90002388_230	Lymphocyte count	1.000000e-09

EFO canonical traits (22, from GWAS)

EFO ID	Trait name
EFO:0004309	platelet count
EFO:0007991	eosinophil percentage of leukocytes
EFO:0004842	eosinophil count
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007984	platelet component distribution width
EFO:0007996	eosinophil percentage of granulocytes
EFO:0004833	neutrophil count
EFO:0005090	basophil count
EFO:0009188	Red cell distribution width
EFO:0007994	neutrophil percentage of granulocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0008378	mosquito bite reaction size measurement
EFO:0004695	intraocular pressure measurement
EFO:0005213	central corneal thickness
EFO:0004760	t-tau measurement
EFO:0004337	intelligence
EFO:0004784	self reported educational attainment
EFO:0004614	apolipoprotein A 1 measurement
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0011018	brain-derived neurotrophic factor measurement
EFO:0004587	lymphocyte count
EFO:0004736	aspartate aminotransferase measurement

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D016649	Primary Ovarian Insufficiency	C12.050.351.500.056.630.750; C12.100.250.056.630.750; C19.391.630.750

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (11): CHEMBL1795186 (SINGLE PROTEIN), CHEMBL4296135 (PROTEIN-PROTEIN INTERACTION), CHEMBL4296144 (PROTEIN-PROTEIN INTERACTION), CHEMBL4296150 (PROTEIN-PROTEIN INTERACTION), CHEMBL4296614 (PROTEIN FAMILY), CHEMBL4523753 (PROTEIN-PROTEIN INTERACTION), CHEMBL5291943 (SELECTIVITY GROUP), CHEMBL5291974 (PROTEIN FAMILY), CHEMBL6193818 (PROTEIN-PROTEIN INTERACTION), CHEMBL6195603 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

8 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 6,439 (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
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
rs467387	BRD3		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 (11 total), top 11:

Ligand	Action	Affinity	Parameter
ARV-771	Inhibition	8.12	pKd
GW841819X	Inhibition	7.55	pIC50
molibresib	Inhibition	7.37	pIC50
WNY0824	Inhibition	6.82	pIC50
MS363	Inhibition	6.62	pKi
I-BET151	Inhibition	6.6	pIC50
compound 38 [PMID: 24000170]	Inhibition	6.6	pIC50
apabetalone	Antagonist	6.55	pIC50
XD14	Inhibition	6.42	pKd
compound 36 [PMID: 24000170]	Inhibition	6.3	pIC50
LY 294002	Inhibition	6.03	pKd

Binding affinities (BindingDB)

565 measured of 607 human assays (607 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
Ethyl 6-(4-chlorophenyl)-2-(3,6-dihydro-2H-pyran-4-yl)-5-(3,8-dimethyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-3-methyl-4-oxo-5,6-dihydropyrrolo[3,4-b]pyrrole-1(4H)-carboxylate	IC50	11 nM	US-9550796: Pyrrolopyrrolone derivatives and their use as BET inhibitors
(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
6-(4-chlorophenyl)-5-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-6-yl)-N,1-dimethyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrole-3-carboxamide	IC50	12 nM	US-9550796: Pyrrolopyrrolone derivatives and their use as BET inhibitors
(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
(R)-6-(4-chlorophenyl)-5-(3,7-dimethyl-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)-2-(2-methoxypyridin-3-yl)-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
3-(azetidin-3-yl)-6-(4-chlorophenyl)-5-(3,7-dimethyl-3H-[1,2,3]triazolo[4,5-b]pyridin-5-yl)-1-methyl-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one	IC50	13 nM	US-9550796: Pyrrolopyrrolone derivatives and their use as BET inhibitors
(R)-6-(4-chlorophenyl)-2-(3,6-dihydro-2H-pyran-4-yl)-5-(3,8-dimethyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-1-methyl-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
6-(4-chlorophenyl)-2-(3,6-dihydro-2H-pyran-4-yl)-5-(3,7-dimethyl-3H-[1,2,3]triazolo[4,5-b]pyridin-5-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
Ethyl 6-(4-chlorophenyl)-5-(3,8-dimethyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-2-(2-methoxypyridin-3-yl)-3-methyl-4-oxo-5,6-dihydropyrrolo[3,4-b]pyrrole-1(4H)-carboxylate	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
N-(6-(4-chlorophenyl)-5-(1,4-dimethyl-1H-benzo[d][1,2,3]triazol-6-yl)-1-methyl-4-oxo-1,4,5,6-tetrahydropyrrolo[3,4-b]pyrrol-3-yl)acetamide	IC50	15 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)-1,2-dimethyl-5,6-dihydropyrrolo[3,4-b]pyrrol-4(1H)-one	IC50	15 nM	US-9550796: Pyrrolopyrrolone derivatives and their use as BET inhibitors
Ethyl 6-(4-chlorophenyl)-3-cyclopropyl-5-(3,8-dimethyl-[1,2,4]triazolo[4,3-a]pyridin-6-yl)-4-oxo-5,6-dihydropyrrolo[3,4-b]pyrrole-1(4H)-carboxylate	IC50	15 nM	US-9550796: Pyrrolopyrrolone derivatives and their use as BET inhibitors

ChEMBL bioactivities

1345 potent at pChembl≥5 of 1436 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.74	Ki	0.18	nM	CHEMBL4228445
9.68	Ki	0.21	nM	CHEMBL4228445
9.60	IC50	0.2512	nM	CHEMBL2177300
9.57	Kd	0.27	nM	CHEMBL4648912
9.47	Kd	0.34	nM	CHEMBL4648912
9.31	Kd	0.49	nM	CHEMBL4173488
9.28	Kd	0.52	nM	CHEMBL4173488
9.21	Kd	0.61	nM	CHEMBL4648912
9.20	IC50	0.631	nM	CHEMBL2177300
9.19	Kd	0.65	nM	CHEMBL3926851
9.19	Ki	0.65	nM	CHEMBL4164015
9.18	Kd	0.66	nM	CHEMBL3926851
9.16	Kd	0.69	nM	CHEMBL4171228
9.14	Kd	0.73	nM	CHEMBL4171228
9.09	Ki	0.82	nM	CHEMBL5893845
9.06	IC50	0.88	nM	ABBV-744
9.00	Kd	1	nM	CHEMBL4440098
9.00	Ki	1	nM	CHEMBL5935595
8.96	IC50	1.1	nM	EZOBRESIB
8.96	Ki	1.1	nM	CHEMBL5752076
8.92	Ki	1.2	nM	CHEMBL5772518
8.90	IC50	1.259	nM	CHEMBL4869149
8.89	Ki	1.3	nM	CHEMBL6029352
8.89	Ki	1.3	nM	CHEMBL5924034
8.89	IC50	1.3	nM	ABBV-744
8.85	IC50	1.4	nM	ABBV-744
8.85	Ki	1.4	nM	CHEMBL5750643
8.80	IC50	1.6	nM	CHEMBL4859923
8.77	Kd	1.7	nM	CHEMBL3926851
8.72	IC50	1.9	nM	CHEMBL4228445
8.72	IC50	1.9	nM	CHEMBL5087175
8.70	IC50	1.995	nM	CHEMBL2177300
8.70	Kd	2	nM	CHEMBL4171228
8.67	Ki	2.16	nM	CHEMBL5394107
8.66	Ki	2.2	nM	CHEMBL5856962
8.65	Ki	2.26	nM	CHEMBL5423636
8.65	Ki	2.24	nM	CHEMBL5435922
8.64	Kd	2.3	nM	CHEMBL5274024
8.64	Ki	2.3	nM	CHEMBL5962068
8.61	Ki	2.46	nM	CHEMBL5437043
8.61	Ki	2.45	nM	CHEMBL5418787
8.60	Ki	2.5	nM	CHEMBL4555209
8.59	Kd	2.6	nM	CHEMBL4528047
8.59	Ki	2.6	nM	CHEMBL4171228
8.55	Ki	2.8	nM	CHEMBL5432216
8.55	Kd	2.8	nM	CHEMBL5590067
8.54	Kd	2.9	nM	CHEMBL5274024
8.52	IC50	3	nM	CHEMBL4780530
8.50	Kd	3.162	nM	GSK973
8.49	Ki	3.2	nM	CHEMBL3581661

PubChem BioAssay actives

596 with measured affinity, of 1262 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
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	1387715: Inhibition of FAM-labeled ZBA248 binding to recombinant N-terminal His6-tagged BRD3 bromodomain 1 (24 to 144 residues) (unknown origin) expressed in Escherichia coli Rosetta2 DE3 after 30 mins by fluorescence polarization assay	ki	0.0002	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	1652236: Binding affinity to human partial length BRD3 bromodomain 1 (P24 to E144 residues) expressed in bacterial expression system by BROMOscan assay	kd	0.0003	uM
4-[(2S,4R)-1-acetyl-4-(4-chloroanilino)-2-methyl-3,4-dihydro-2H-quinolin-6-yl]benzoic acid	1165977: Binding affinity to full-length BRD4 short isoform (unknown origin) by BROMOscan assay	ic50	0.0003	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	1356119: Binding affinity to human BRD3 bromodomain 1 (P24 to E144 residues) expressed in bacterial expression system by BROMOscan assay	kd	0.0005	uM
4-[2-cyclopropyl-7-(6-methylquinolin-5-yl)-3H-benzimidazol-5-yl]-3,5-dimethyl-1,2-oxazole	1535663: Binding affinity to human partial length BRD3 bromodomain 2 (G306 to P416 residues) expressed in bacterial expression system after 1 hr by bromoscan assay	kd	0.0006	uM
4-(6-methoxy-2-methyl-4-quinolin-4-yl-9H-pyrimido[4,5-b]indol-7-yl)-3,5-dimethyl-1,2-oxazole	1371270: Binding affinity to human partial length BRD3 bromodomain 2 (G306 to P416 residues) expressed in bacterial expression system by BROMOscan assay	kd	0.0007	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	1905949: Inhibition of C-terminal His6-tagged BRD3 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	0.0009	uM
6-[2-(2,4-difluorophenoxy)-5-(ethylsulfonylmethyl)-3-pyridinyl]-8-methyl-2H-pyrrolo[1,2-a]pyrazin-1-one	1605885: Binding affinity to human partial length BRD3 BD2 (G306 to P416 residues) expressed in bacterial expression system by bromoscan assay	kd	0.0010	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	1830336: Inhibition of human BRD3 measured by TR-FRET assay	ic50	0.0011	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	1777124: Inhibition of recombinant human BRD3 BD2 (306 to 416 residues) expressed in bacterial expression system by bromoscan assay	ic50	0.0013	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	1870416: Inhibition of BRD3 (unknown origin)	ic50	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	1830336: Inhibition of human BRD3 measured by TR-FRET assay	ic50	0.0019	uM
3-[7-[6-[[4-[6-(4-chloroanilino)-1-methyl-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepin-8-yl]phenyl]methylamino]hexyl]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1970078: Binding affinity to recombinant human BRD3 BD2 (306 to 417 residues) assessed as inhibition constant by fluorescence polarization binding assay	ki	0.0022	uM
3-[7-[4-[[4-[6-(4-chloroanilino)-1-methyl-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepin-8-yl]phenyl]methylamino]butyl]-3-oxo-1H-isoindol-2-yl]-1-methylpiperidine-2,6-dione	1970078: Binding affinity to recombinant human BRD3 BD2 (306 to 417 residues) assessed as inhibition constant by fluorescence polarization binding assay	ki	0.0022	uM
3-[7-[7-[[4-[6-(4-chloroanilino)-1-methyl-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepin-8-yl]phenyl]methylamino]heptyl]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1970078: Binding affinity to recombinant human BRD3 BD2 (306 to 417 residues) assessed as inhibition constant by fluorescence polarization binding assay	ki	0.0023	uM
3-[7-[4-[[4-[6-(4-chloroanilino)-1-methyl-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepin-8-yl]phenyl]methylamino]butyl]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1970078: Binding affinity to recombinant human BRD3 BD2 (306 to 417 residues) assessed as inhibition constant by fluorescence polarization binding assay	ki	0.0024	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	1584510: Binding affinity to human BRD3 BD1 (24 to 144 residues) by fluorescence polarization assay	ki	0.0025	uM
3-[7-[3-[[4-[6-(4-chloroanilino)-1-methyl-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepin-8-yl]phenyl]methylamino]propyl]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1970078: Binding affinity to recombinant human BRD3 BD2 (306 to 417 residues) assessed as inhibition constant by fluorescence polarization binding assay	ki	0.0025	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	1565554: Binding affinity to human partial length BRD3 BD2 (G306 to P416 residues) expressed in bacterial expression system by bromoscan assay	kd	0.0026	uM
3-[7-[4-[[4-[6-(4-chloroanilino)-1-methyl-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepin-8-yl]phenyl]methyl-methylamino]butyl]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1970078: Binding affinity to recombinant human BRD3 BD2 (306 to 417 residues) assessed as inhibition constant by fluorescence polarization binding assay	ki	0.0028	uM
7-[2-(cyclopropylmethoxy)phenyl]-5-methyl-2-[[(2R)-2-methyl-4-methylsulfonylpiperazin-1-yl]methyl]furo[3,2-c]pyridin-4-one	2112653: Binding affinity to BRD3 BD1 (unknown origin) assessed as dissociation constant by BROMOscan assay	kd	0.0028	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	1711613: Inhibition of BRD3 BD1 (unknown origin) using biotinylated JQ1 analog as substrate measured after 20 mins by AlphaLISA assay	ic50	0.0030	uM
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	1230002: Displacement of FAM-labeled ZBA248 from BRD3 BD2 (306 to 417 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay	ki	0.0032	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	1946240: Protac activity at VHL/BRD3 in HEK293 cells assessed as degradation of BRD3 incubated for 4 hrs by Western blot analysis	ec50	0.0033	uM
1,3-dimethyl-5-[2-(oxan-4-yl)-3-[2-(trifluoromethoxy)ethyl]benzimidazol-5-yl]pyridin-2-one	1938462: Binding affinity BRD3 (unknown origin) assessed as dissociation constant	kd	0.0035	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	1721394: Binding affinity to full length BRD3 BD1 in human HuT78 cell lysates incubated for 45 mins by liquid chromatography-mass spectrometry based chemoproteomic binding assay	kd	0.0040	uM
1,3-dimethyl-5-[1-[[(3S)-1-(1-propan-2-ylpiperidine-4-carbonyl)piperidin-3-yl]methyl]benzimidazol-2-yl]pyridin-2-one	2022142: Inhibition of BRD3 BD1 (unknown origin) by BROMOscan assay	kd	0.0040	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	1230002: Displacement of FAM-labeled ZBA248 from BRD3 BD2 (306 to 417 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay	ki	0.0040	uM
4-[1-(3,5-diethyl-1H-pyrazol-4-yl)-8-methoxy-5H-pyrido[4,3-b]indol-7-yl]-3,5-dimethyl-1,2-oxazole	1230002: Displacement of FAM-labeled ZBA248 from BRD3 BD2 (306 to 417 amino acid residues) (unknown origin) expressed in Rosetta2 DE3 cells after 30 mins by fluorescence polarization assay	ki	0.0042	uM
3-[7-[6-[[4-[6-(4-chloroanilino)-1-methyl-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepin-8-yl]phenyl]methylamino]hex-1-ynyl]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1970078: Binding affinity to recombinant human BRD3 BD2 (306 to 417 residues) assessed as inhibition constant by fluorescence polarization binding assay	ki	0.0047	uM
3-[7-[3-[[4-[6-(4-chloroanilino)-1-methyl-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepin-8-yl]phenyl]methylamino]prop-1-ynyl]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1970078: Binding affinity to recombinant human BRD3 BD2 (306 to 417 residues) assessed as inhibition constant by fluorescence polarization binding assay	ki	0.0048	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	1905949: Inhibition of C-terminal His6-tagged BRD3 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	0.0049	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	1928098: PROTAC activity at BRD3/VHL in human 22Rv1 cells assessed as protein degradation measured after 16 hrs	ec50	0.0050	uM
6-[hydroxy(phenyl)methyl]-2-N-methyl-4-N-[(1S,2S)-2-methylcyclopropyl]pyridine-2,4-dicarboxamide	1751394: Binding affinity to human partial length BRD3 BD 2 (G306 to P416 residues) expressed in bacterial expression system by BROMOscan assay	kd	0.0050	uM
3-[7-[5-[[4-[6-(4-chloroanilino)-1-methyl-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepin-8-yl]phenyl]methylamino]pent-1-ynyl]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1970078: Binding affinity to recombinant human BRD3 BD2 (306 to 417 residues) assessed as inhibition constant by fluorescence polarization binding assay	ki	0.0050	uM
2-[4-[6-(4-chloroanilino)-1-methyl-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepin-8-yl]pyrazol-1-yl]-N-[5-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-4-yl]pent-4-ynyl]acetamide	1970078: Binding affinity to recombinant human BRD3 BD2 (306 to 417 residues) assessed as inhibition constant by fluorescence polarization binding assay	ki	0.0050	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	1905949: Inhibition of C-terminal His6-tagged BRD3 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	0.0053	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-[[2-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-4-yl]oxyacetyl]amino]butyl]acetamide	1970078: Binding affinity to recombinant human BRD3 BD2 (306 to 417 residues) assessed as inhibition constant by fluorescence polarization binding assay	ki	0.0053	uM
3-[7-[5-[[4-[6-(4-chloroanilino)-1-methyl-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepin-8-yl]phenyl]methylamino]pentyl]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1970078: Binding affinity to recombinant human BRD3 BD2 (306 to 417 residues) assessed as inhibition constant by fluorescence polarization binding assay	ki	0.0054	uM
N-[4-[(7-methoxy-1-methyl-[1,2,4]triazolo[4,3-a]quinoxalin-4-yl)amino]butyl]-3-methylbutanamide	2100765: Binding affinity to human BRD3 assessed as dissociation constant by ITC analysis	kd	0.0055	uM
5-methyl-2-[[(2R)-2-methyl-4-methylsulfonylpiperazin-1-yl]methyl]-7-[3-(methylsulfonylmethyl)phenyl]furo[3,2-c]pyridin-4-one	2112653: Binding affinity to BRD3 BD1 (unknown origin) assessed as dissociation constant by BROMOscan assay	kd	0.0055	uM
3-[7-[4-[[4-[6-(4-chloroanilino)-1-methyl-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepin-8-yl]phenyl]methylamino]but-1-ynyl]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1970078: Binding affinity to recombinant human BRD3 BD2 (306 to 417 residues) assessed as inhibition constant by fluorescence polarization binding assay	ki	0.0057	uM
3-[7-[7-[[4-[6-(4-chloroanilino)-1-methyl-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepin-8-yl]phenyl]methylamino]hept-1-ynyl]-3-oxo-1H-isoindol-2-yl]piperidine-2,6-dione	1970078: Binding affinity to recombinant human BRD3 BD2 (306 to 417 residues) assessed as inhibition constant by fluorescence polarization binding assay	ki	0.0059	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	1998776: Inhibition of N-terminal his-tagged human recombinant BRD3 BD2 (1 to 434 residues) expressed in Escherichia coli by AlphaScreen assay	ic50	0.0060	uM
(2S,4R)-1-acetyl-4-[(5-chloropyrimidin-2-yl)amino]-2-methyl-3,4-dihydro-2H-quinoline-6-carboxamide	1900666: Binding affinity to BRD3 BD2 (unknown origin) assessed as dissociation constant	kd	0.0063	uM
2-[4-[6-(4-chloroanilino)-1-methyl-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepin-8-yl]pyrazol-1-yl]-N-[7-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-4-yl]hept-6-ynyl]acetamide	1970078: Binding affinity to recombinant human BRD3 BD2 (306 to 417 residues) assessed as inhibition constant by fluorescence polarization binding assay	ki	0.0063	uM
2-[4-[6-(4-chloroanilino)-1-methyl-5,6-dihydro-4H-[1,2,4]triazolo[4,3-a][1]benzazepin-8-yl]pyrazol-1-yl]-N-[6-[2-(2,6-dioxopiperidin-3-yl)-1-oxo-3H-isoindol-4-yl]hex-5-ynyl]acetamide	1970078: Binding affinity to recombinant human BRD3 BD2 (306 to 417 residues) assessed as inhibition constant by fluorescence polarization binding assay	ki	0.0066	uM
N-[2-[2-(2-aminoethoxy)ethoxy]ethyl]-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	1515641: Inhibition of BRD3 (unknown origin) by TR-FRET assay	ic50	0.0070	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	decreases reaction, decreases expression, increases expression, affects binding	3
sodium arsenite	decreases expression, affects expression	2
Benzo(a)pyrene	decreases methylation, increases expression	2
Phenylmercuric Acetate	affects cotreatment, decreases expression	2
Valproic Acid	affects expression, decreases expression, increases methylation	2
Aflatoxin B1	increases methylation, decreases expression	2
OTX015	decreases expression	1
FR900359	increases phosphorylation	1
TAK-243	decreases sumoylation	1
dicrotophos	increases expression	1
perfluorooctanoic acid	decreases expression	1
coumarin	affects phosphorylation	1
N,N,N’,N’-tetrakis(2-pyridylmethyl)ethylenediamine	decreases expression	1
tamibarotene	affects expression	1
azoxystrobin	decreases expression	1
deguelin	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, decreases expression	1
pyrimidifen	decreases expression	1
abrine	decreases expression	1
pyrachlostrobin	decreases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
bisphenol S	affects cotreatment, decreases expression	1
Resveratrol	affects cotreatment, decreases expression	1
Antimycin A	decreases expression	1
Caffeine	decreases phosphorylation	1
Carbamazepine	affects expression	1
Coumestrol	decreases expression	1
Dexamethasone	affects cotreatment, decreases expression	1
Dimethyl Sulfoxide	increases expression	1
Indomethacin	affects cotreatment, decreases expression	1

ChEMBL screening assays

639 unique, capped per target: 614 binding, 20 functional, 5 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1832852	Binding	Binding affinity to second bromodomain of BRD3 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
CHEMBL4668942	ADMET	Displacement of Alexa Fluor 647 labelled ligand from 6His-Thr tagged BRD3 BD1/BD2 Y348A mutant (1 to 435 residues) (unknown origin) measured after 30 mins by TR-FRET assay	Design and Synthesis of a Highly Selective and In Vivo-Capable Inhibitor of the Second Bromodomain of the Bromodomain and Extra Terminal Domain Family of Proteins. — J Med Chem
CHEMBL5210060	Functional	Affinity Phenotypic Cellular interaction (Cell Proliferation (Cell TiterGlo assay Promega in NMC 11060 cells)) EUB0000330a BRD3	Affinity Phenotypic Cellular Literature for EUbOPEN Chemogenomics Library wave 3

Cellosaurus cell lines

11 cell lines: 8 cancer cell line, 3 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_B2T0	Abcam HEK293T BRD3 KO	Transformed cell line	Female
CVCL_B8C4	Abcam HCT 116 BRD3 KO	Cancer cell line	Male
CVCL_B8T4	Abcam MCF-7 BRD3 KO	Cancer cell line	Female
CVCL_B9EA	Abcam A-549 BRD3 KO	Cancer cell line	Male
CVCL_C8Z0	10326	Cancer cell line
CVCL_KW04	InCELL Hunter HEK 293 BRD3(1) Bromodomain	Transformed cell line	Female
CVCL_KW05	InCELL Hunter HEK 293 BRD3(1,2) Bromodomain	Transformed cell line	Female
CVCL_SF56	HAP1 BRD3 (-) 1	Cancer cell line	Male
CVCL_SF57	HAP1 BRD3 (-) 2	Cancer cell line	Male
CVCL_SF58	HAP1 BRD3 (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00417066	PHASE4	COMPLETED	Flexible GnRH Antagonist vs Flare up GnRH Agonist Protocol in Poor Responders
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00837616	PHASE4	COMPLETED	Estrogen Dosing in Turner Syndrome: Pharmacology and Metabolism
NCT01853501	PHASE4	UNKNOWN	Effects of ADSC Therapy in Women With POF
NCT02783937	PHASE4	COMPLETED	Filgrastim for Premature Ovarian Insufficiency
NCT03535480	PHASE4	UNKNOWN	Autologous Bone Marrow Stem Cell Ovarian Transplantation to Restore Ovarian Function in Premature Ovarian Failure
NCT00140998	PHASE3	COMPLETED	Estrogen Treatment (Oral vs. Patches) in Turner Syndrome
NCT00001951	PHASE2	COMPLETED	Hormone Replacement in Young Women With Premature Ovarian Failure
NCT00370019	PHASE2	WITHDRAWN	Effects of an Estrogen Replacement Therapy Skin Patch on Ovulation in Women With Premature Ovarian Failure
NCT00429494	PHASE2	COMPLETED	GnRH Analogue for Ovarian Function Preservation in Hematopoietic Stem Cell Transplantation Patients
NCT03816852	PHASE2	SUSPENDED	The Safety and Efficiency Study of Mesenchymal Stem Cell (19#iSCLife®-POI) in Premature Ovarian Insufficiency
NCT04536467	PHASE2	UNKNOWN	Prevention of Chemotherapy-Induced Ovarian Failure With Goserelin in Premenopausal Lymphoma Patients
NCT06117982	PHASE2	COMPLETED	The Impact of Granulocyte Colony Stimulating Factor on Premature Ovarian Insufficiency
NCT02912104	PHASE1	COMPLETED	A Therapeutic Trial of Human Amniotic Epithelial Cells Transplantation for Primary Ovarian Failure
NCT03178695	PHASE1	COMPLETED	Inovium Ovarian Rejuvenation Trials
NCT04815213	PHASE1	ACTIVE_NOT_RECRUITING	The Use of Expandeded Mesenchymal Stromal Cells (MSC) in Premature Ovarian Failure (POF) in Adult Humans
NCT05138367	PHASE1	COMPLETED	Effects of UCA-PSCs in Women With POF
NCT06132542	PHASE1	UNKNOWN	Autologous ADMSC Transplantation in Patients With POI
NCT00948857	PHASE2/PHASE3	TERMINATED	Dehydroepiandrosterone (DHEA) Treatment and Premature Ovarian Failure (POF)
NCT04031456	PHASE2/PHASE3	RECRUITING	Autologous PRP Infusion May Restore Ovarian Function and May Promote Folliculogenesis in POI Patients
NCT02043743	PHASE1/PHASE2	UNKNOWN	Autologous Stem Cells Transplantation in Patients With Idiopathic and Drug Induced Premature Ovarian Failure
NCT02062931	PHASE1/PHASE2	UNKNOWN	Autologous Mesenchymal Stem Cells Transplantation In Women With Premature Ovarian Failure
NCT02151890	PHASE1/PHASE2	COMPLETED	Pregnancy After Stem Cell Transplantation in Premature Ovarian Failure
NCT02372474	PHASE1/PHASE2	COMPLETED	It is a Real The First Baby Of Autologous Stem Cell Therapy in Premature Ovarian Failure
NCT02603744	PHASE1/PHASE2	UNKNOWN	Autologous Adipose Derived Mesenchymal Stromal Cells Transplantation in Women With Premature Ovarian Failure (POF)
NCT02644447	PHASE1/PHASE2	COMPLETED	Transplantation of HUC-MSCs With Injectable Collagen Scaffold for POF
NCT03069209	PHASE1/PHASE2	UNKNOWN	Autologous Bone Marrow-Derived Stem Cell Transplantation in Patients With Premature Ovarian Failure (POF)
NCT03985462	PHASE1/PHASE2	WITHDRAWN	Very Small Embryonic-like Stem Cells for Ovary
NCT04009473	PHASE1/PHASE2	UNKNOWN	Stem Cell Therapy and Growth Factor Ovarian in Vitro Activation
NCT04071574	PHASE1/PHASE2	COMPLETED	Comparative Study on the Efficacy of Ovarian Stimulation Protocols on the Success Rate of ICSI in Female Infertility
NCT04922398	PHASE1/PHASE2	UNKNOWN	Ovarian Injection of PRP (Platelet -Rich Plasma) Vs Normal Saline in Premature Ovarian Insufficiency
NCT05462379	PHASE1/PHASE2	ACTIVE_NOT_RECRUITING	Autologous Heterotopic Fresh Ovarian Graft in Woman With LACC Eligible for Pelvic Radiotherapy Treatment.
NCT06202547	PHASE1/PHASE2	UNKNOWN	Intra-ovarian Injection of MSC-EVs in Idiopathic Premature Ovarian Failure
NCT01129947	EARLY_PHASE1	WITHDRAWN	The Use of DHEA in Women With Premature Ovarian Failure
NCT05522634	EARLY_PHASE1	UNKNOWN	A Clinical Study of Chinese Herbal Compound TJAOA101 in the Treatment of Premature Ovarian Insufficiency
NCT07308327	EARLY_PHASE1	ACTIVE_NOT_RECRUITING	The Influence of Gut Microbiota on Ovarian Function: A Single-center, Randomized,Double Blind, Parallel-controlled, Exploratory Clinical Trial
NCT00001275	Not specified	COMPLETED	Ovarian Follicle Function in Patients With Primary Ovarian Failure
NCT00001306	Not specified	COMPLETED	Steroid Therapy in Autoimmune Premature Ovarian Failure
NCT00006156	Not specified	COMPLETED	Feasibility Study for Development of an Early Test for Ovarian Failure
NCT00119925	Not specified	UNKNOWN	‘SPRING’-Study: Subfertility Guidelines: Patient Related Implementation in the Netherlands Among Gynaecologists