BRD4

Summary

BRD4 (bromodomain containing 4, HGNC:13575) is a protein-coding gene on chromosome 19p13.12, encoding Bromodomain-containing protein 4 (O60885). Chromatin reader protein that recognizes and binds acetylated histones and plays a key role in transmission of epigenetic memory across cell divisions and transcription regulation. It is a common-essential gene (DepMap: required in 94.7% of cancer cell lines).

The protein encoded by this gene is homologous to the murine protein MCAP, which associates with chromosomes during mitosis, and to the human RING3 protein, a serine/threonine kinase. Each of these proteins contains two bromodomains, a conserved sequence motif which may be involved in chromatin targeting. This gene has been implicated as the chromosome 19 target of translocation t(15;19)(q13;p13.1), which defines an upper respiratory tract carcinoma in young people. Two alternatively spliced transcript variants have been described.

Source: NCBI Gene 23476 — RefSeq curated summary.

At a glance

• Gene–disease (curated): syndromic intellectual disability (Definitive, ClinGen) — +3 more curated relationships
• GWAS associations: 5
• Clinical variants (ClinVar): 967 total — 16 pathogenic, 18 likely-pathogenic
• Phenotypes (HPO): 136
• Druggable target: yes — 31 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): activating (oncogene-like) across 4 cancer types
• Cancer dependency (DepMap): dependent in 94.7% of screened cell lines (common-essential)
• Transcription factor: yes — 14 downstream targets (CollecTRI)
• MANE Select transcript: NM_001379291

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:13575
Approved symbol	BRD4
Name	bromodomain containing 4
Location	19p13.12
Locus type	gene with protein product
Status	Approved
Aliases	HUNKI, MCAP, CAP, HUNK1, FSHRG4
Ensembl gene	ENSG00000141867
Ensembl biotype	protein_coding
OMIM	608749
Entrez	23476

Gene structure

Transcript identifiers

Ensembl transcripts: 13 — 6 protein_coding, 3 retained_intron, 3 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000263377, ENST00000360016, ENST00000371835, ENST00000594066, ENST00000594841, ENST00000594842, ENST00000595926, ENST00000597315, ENST00000601071, ENST00000601941, ENST00000602230, ENST00000678800, ENST00000679869

RefSeq mRNA: 5 — MANE Select: NM_001379291 NM_001330384, NM_001379291, NM_001379292, NM_014299, NM_058243

CCDS: CCDS12328, CCDS46004, CCDS82307

Canonical transcript exons

ENST00000679869 — 20 exons

Exon	Start	End
ENSE00000348853	15264404	15264766
ENSE00000689048	15265354	15265643
ENSE00000689052	15256064	15256263
ENSE00000689053	15255297	15255592
ENSE00000951121	15239059	15239264
ENSE00000951122	15238743	15238980
ENSE00001055976	15242900	15243487
ENSE00001055981	15235519	15238445
ENSE00001055985	15244231	15244600
ENSE00001113199	15239392	15239522
ENSE00001113200	15239659	15239821
ENSE00001113202	15272815	15273133
ENSE00001113203	15244710	15244762
ENSE00001136676	15239910	15240022
ENSE00001187704	15254152	15254262
ENSE00003494168	15268905	15269042
ENSE00003506585	15256964	15257173
ENSE00003548258	15267416	15267551
ENSE00003680162	15263420	15263548
ENSE00003761910	15332290	15332539

Expression profiles

Bgee: expression breadth ubiquitous, 300 present calls, max score 99.22.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 42.9545 / max 550.3680, expressed in 1821 samples.

FANTOM5 promoters (8 alternative TSS)

Promoter ID	TPM avg	Samples expressed
179732	17.9095	1797
179733	16.1414	1796
179725	3.4739	1439
179724	2.0013	1088
179719	1.1921	771
179730	1.1759	802
208712	0.7088	417
179731	0.3516	135

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
buccal mucosa cell	CL:0002336	99.22	gold quality
sural nerve	UBERON:0015488	99.02	gold quality
tendon of biceps brachii	UBERON:0008188	98.15	gold quality
nipple	UBERON:0002030	98.10	gold quality
medial globus pallidus	UBERON:0002477	96.83	gold quality
pylorus	UBERON:0001166	96.68	gold quality
secondary oocyte	CL:0000655	96.51	gold quality
cardia of stomach	UBERON:0001162	96.27	gold quality
oocyte	CL:0000023	96.05	gold quality
renal medulla	UBERON:0000362	95.88	gold quality
globus pallidus	UBERON:0001875	95.68	gold quality
vena cava	UBERON:0004087	95.58	gold quality
cartilage tissue	UBERON:0002418	95.49	gold quality
entorhinal cortex	UBERON:0002728	95.44	gold quality
saphenous vein	UBERON:0007318	94.85	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	94.67	gold quality
seminal vesicle	UBERON:0000998	94.62	gold quality
postcentral gyrus	UBERON:0002581	94.53	gold quality
parietal lobe	UBERON:0001872	94.47	gold quality
blood	UBERON:0000178	94.36	gold quality
middle temporal gyrus	UBERON:0002771	94.36	gold quality
gastrocnemius	UBERON:0001388	94.31	gold quality
inferior olivary complex	UBERON:0002127	94.29	gold quality
olfactory bulb	UBERON:0002264	94.27	gold quality
trabecular bone tissue	UBERON:0002483	94.18	gold quality
mammalian vulva	UBERON:0000997	94.10	gold quality
dorsal root ganglion	UBERON:0000044	93.81	gold quality
urethra	UBERON:0000057	93.73	gold quality
bone marrow cell	CL:0002092	93.72	gold quality
muscle of leg	UBERON:0001383	93.72	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	8.19
E-GEOD-110499	no	403.36
E-MTAB-3929	no	257.94

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

14 targets.

Target	Regulation
ANKRD37
BCL2
CCND1	Activation
DCPS	Activation
DMAP1
HNRNPH1
HS1BP3
IL7R
KAT5
KDM5C	Activation
MLF2
PIM2	Activation
STC2
TNF

Upstream regulators (CollecTRI, top): JMJD6, MYC, NPM1

miRNA regulators (miRDB)

31 targeting BRD4, 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-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-6870-5P	99.99	68.55	2115
HSA-MIR-3065-5P	99.97	71.56	3281
HSA-MIR-4447	99.85	67.81	2900
HSA-MIR-765	99.84	68.24	2442
HSA-MIR-3121-3P	99.82	71.96	3630
HSA-MIR-11181-3P	99.75	66.38	2205
HSA-MIR-4516	99.61	67.78	3390
HSA-MIR-6132	99.60	65.83	1554
HSA-MIR-6836-5P	99.60	65.62	1538
HSA-MIR-4472	99.56	66.08	1478
HSA-MIR-892A	99.54	68.16	1141
HSA-MIR-7159-5P	99.53	72.12	2472
HSA-MIR-5787	99.22	67.86	2628
HSA-MIR-4784	99.15	67.41	1733
HSA-MIR-491-5P	99.13	65.98	1468
HSA-MIR-4434	99.10	67.01	1984
HSA-MIR-5703	99.10	67.09	2053
HSA-MIR-1286	99.09	66.23	1046
HSA-MIR-3150B-3P	98.81	67.21	1728
HSA-MIR-4272	98.76	68.74	1810
HSA-MIR-5197-3P	98.71	67.05	1905
HSA-MIR-767-3P	98.61	67.69	1192
HSA-MIR-3972	97.19	66.46	808
HSA-MIR-1202	97.19	66.43	827
HSA-MIR-1913	97.07	66.20	1417
HSA-MIR-6796-5P	95.37	66.08	1120
HSA-MIR-548AD-3P	94.39	66.04	350

Functional genomics

DepMap (CRISPR cell-line fitness): dependent in 94.7% of screened cell lines, common-essential.

Literature-anchored findings (GeneRIF, showing 40)

• brd4 binds to replication factor C and inhibits progression to S phase (PMID:12192049)
• E2 protein interacts with Brd4 and tethers the viral DNA to the host mitotic chromosomes. (PMID:15109495)
• Data identif a Rap GTPase-activating protein, signal-induced proliferation-associated protein 1 (SPA-1), as a factor that interacts with Brd4. (PMID:15456879)
• Brd4 has recently been proposed to mediate the association between bovine papilomavirus1 E2 and mitotic chromosomes. (PMID:15795266)
• Wild type Brd4 inhibits G(1) to S progression and we also found that the Brd4-NUT fusion augments the inhibition of progression to S phase compared with wild type Brd4. (PMID:15994877)
• establish a broader role for Brd4 in the papillomavirus life cycle than as the chromosome tether for papillomavirus E2 during mitosis (PMID:16611886)
• Brd4 is a component of human papillomavirus-assembled transcriptional silencing complex with a novel function as a cellular cofactor modulating viral gene expression. (PMID:16921027)
• there are distinct functional roles for the two bromodomain proteins RING3/Brd2 and Brd4 in LANA binding (PMID:16940503)
• The major papillomavirus E2-binding protein was identified by mass spectrometry and western blotting as the long isoform of Brd4.[Brd4] (PMID:17023018)
• We show the X-ray crystal structure of the carboxy-terminal domain of Brd4 in complex with HPV-16 E2, and with this information have developed a Brd4-Tat fusion protein that is efficiently taken up by different transformed cells harboring HPV plasmids. (PMID:17189190)
• evidence for a Brd4-independent mechanism of E2-mediated repression and suggests that different cellular factors must be involved in E2-mediated transcriptional activation and repression functions. (PMID:17626100)
• Tax may compete and functionally substitute for Brd4 in P-TEFb regulation.Tax and Brd4 compete for binding to P-TEFb through direct interaction with cyclin T1 (PMID:17686863)
• Overexpression of the BRD4 P-TEFb-interacting domain disrupts the interaction between the HIV transactivator Tat and positive transcription elongation factor b and suppresses the ability of Tat to transactivate the HIV promoter (PMID:17690245)
• BRD-NUT fusion proteins contribute to carcinogenesis by associating with chromatin and interfering with epithelial differentiation. (PMID:17934517)
• while the P-TEFb level remains constant, the Brd4-P-TEFb interaction increases dramatically in cells progressing from late mitosis to early G(1). (PMID:18039861)
• The two bromodomains of Brd4 are mainly monomeric in solution; therefore Brd4 should have its own mechanism to reinforce its association with chromatin both in mitotic retention and related cellular processes. (PMID:18500820)
• The authors provide evidence that Brd4 regulates P-TEFb kinase activity by inducing a negative pathway via phosphorylation of CDK9 at threonine 29 (T29) in the HIV transcription initiation complex, inhibiting CDK9 kinase activity. (PMID:18971272)
• coactivator and corepressor function of Brd4 requires at least one intact bromodomain and is mediated by its direct association with E2 proteins encoded by various papillomaviruses (PMID:19038968)
• Brd4 as a novel coactivator of NF-kappaB through specifically binding to acetylated lysine-310 of RelA. (PMID:19103749)
• Bovine papillomavirus type 1 (BPV-1) E2 binds cellular chromatin in complex with Brd4 in both mitotic and interphase cells. (PMID:19129460)
• results indicate that the stability of human papillomavirus E2 is increased upon complex formation with Brd4 (PMID:19211738)
• In addition to Brd4’s role in mediating E2 transcription and genome tethering activities, these data suggest a potential role for Brd4 in regulating E2 stability and protein levels within papillomavirus-infected cells. (PMID:19553317)
• Brd4 is essential for the maintenance of the cell cycle progression mediated at least in part through the control of transcription of the Aurora B kinase cell cycle regulatory gene. (PMID:19596781)
• Abrogation of the interaction between P-TEFb and Brd4 thus provides a mechanism for E2-mediated repression of the viral oncogenes from the integrated viral genomes in cancer cells. (PMID:19846528)
• Studies indicate that KSHV LANA interacts with Brd2 and Brd4. (PMID:20036832)
• T-loop phosphorylated Cdk9 localizes to nuclear speckle domains which may serve as sites of active P-TEFb function and exchange between the Brd4 and 7SK/HEXIM1 regulatory complexes. (PMID:20201073)
• Using a patient-derived cell line, the authors show that p300 sequestration into the chromatin-bound BRD4-NUT fusion protein foci is the principal oncogenic mechanism leading to p53 inactivation. (PMID:20676058)
• Functional studies with Brd4 indicate that the ET domain mediates pTEFb-independent transcriptional activation through a subset of these associated factors, including NSD3. (PMID:21555454)
• study provides a novel mechanism by which the BRD4-NUT oncogene perturbs BRD4 functions to block cellular differentiation and to contribute to the oncogenic progression in the highly aggressive NUT midline carcinoma (PMID:21652721)
• 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)
• model where two BRD4 domains, the second bromodomain and the PID, bind P-TEFb and are required for full transcriptional activation of P-TEFb response genes. (PMID:22084242)
• BRD4 is frequently downregulated by aberrant promoter hypermethylation in human colon cancer cell lines and primary tumors. (PMID:22120039)
• novel structural role of Brd4 in supporting the higher chromatin architecture (PMID:22334664)
• Down-regulation of NF-kappaB transcriptional activity in HIV-associated kidney disease by BRD4 inhibition. (PMID:22645123)
• three CTD kinases, CDK7, CDK9, and BRD4, engage in cross-talk, modulating their subsequent C-terminal domain phosphorylation, and also phosphorylate TAF7 (PMID:23027873)
• The inhibition of bromodomain containing 4 increases Tat-dependent transcriptional elongation and Tat-PTEF-b association. (PMID:23041316)
• BRD4-driven Pol II phosphorylation at serine 2 plays an important role in regulating lineage-specific gene transcription in human CD4+ T cells. (PMID:23086925)
• 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)
• The novel BRD4-NUT fusion in which Exon 15 of BRD4 was fused to Exon 2 of NUT encodes a functional protein that is central to the oncogenic mechanism in these cells. (PMID:23128391)
• Bromodomain protein Brd4 plays a key role in Merkel cell polyomavirus DNA replication (PMID:23144621)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Brd4	ENSMUSG00000024002
drosophila_melanogaster	Acf	FBGN0027620
caenorhabditis_elegans		WBGENE00001470

Paralogs (11): BAZ1B (ENSG00000009954), BAZ2A (ENSG00000076108), CECR2 (ENSG00000099954), KAT2A (ENSG00000108773), KAT2B (ENSG00000114166), BAZ2B (ENSG00000123636), BRDT (ENSG00000137948), BRD3 (ENSG00000169925), BPTF (ENSG00000171634), BAZ1A (ENSG00000198604), BRD2 (ENSG00000204256)

Protein

Protein identifiers

Bromodomain-containing protein 4 — O60885 (reviewed: O60885)

Alternative names: Protein HUNK1

All UniProt accessions (4): O60885, M0QYW0, M0QZD9, M0R0H4

UniProt curated annotations — full annotation on UniProt →

Function. Chromatin reader protein that recognizes and binds acetylated histones and plays a key role in transmission of epigenetic memory across cell divisions and transcription regulation. Remains associated with acetylated chromatin throughout the entire cell cycle and provides epigenetic memory for postmitotic G1 gene transcription by preserving acetylated chromatin status and maintaining high-order chromatin structure. During interphase, plays a key role in regulating the transcription of signal-inducible genes by associating with the P-TEFb complex and recruiting it to promoters. Also recruits P-TEFb complex to distal enhancers, so called anti-pause enhancers in collaboration with JMJD6. BRD4 and JMJD6 are required to form the transcriptionally active P-TEFb complex by displacing negative regulators such as HEXIM1 and 7SKsnRNA complex from P-TEFb, thereby transforming it into an active form that can then phosphorylate the C-terminal domain (CTD) of RNA polymerase II. Regulates differentiation of naive CD4(+) T-cells into T-helper Th17 by promoting recruitment of P-TEFb to promoters. Promotes phosphorylation of ‘Ser-2’ of the C-terminal domain (CTD) of RNA polymerase II. According to a report, directly acts as an atypical protein kinase and mediates phosphorylation of ‘Ser-2’ of the C-terminal domain (CTD) of RNA polymerase II; these data however need additional evidences in vivo. In addition to acetylated histones, also recognizes and binds acetylated RELA, leading to further recruitment of the P-TEFb complex and subsequent activation of NF-kappa-B. Also acts as a regulator of p53/TP53-mediated transcription: following phosphorylation by CK2, recruited to p53/TP53 specific target promoters. Acts as a chromatin insulator in the DNA damage response pathway. Inhibits DNA damage response signaling by recruiting the condensin-2 complex to acetylated histones, leading to chromatin structure remodeling, insulating the region from DNA damage response by limiting spreading of histone H2AX/H2A.x phosphorylation.

Subunit / interactions. Interacts with p53/TP53; the interaction is direct. Interacts (via CTD region) with CDK9 and CCNT1, acting as an associated component of P-TEFb complex. Interacts with RELA (when acetylated at ‘Lys-310’). Interacts (via NET domain) with NSD3, CHD4, BICRA and ATAD5. The interaction with BICRA bridges BRD4 to the GBAF complex. Interacts (via NET domain) with JMJD6 (via JmjC and N-terminal domains); the interaction is stronger in presence of ssRNA and recruits JMJD6 on distal enhancers. Interacts with NSD3. Interacts with NIPBL. Interacts with SMC2. Interacts with NCAPD3. (Microbial infection) Interacts with bovine papillomavirus type 1 regulatory protein E2. This interactions may serve for the tethering of viral genomes to host mitotic chromosomes allowing successful partitioning of the viral genome during cell division. (Microbial infection) Interacts with Epstein-Barr virus (EBV) protein EBNA1; this interaction facilitates transcriptional activation by EBNA1. (Microbial infection) Interacts with human herpes virus-8 (HHV-8) protein LANA.

Subcellular location. Nucleus. Chromosome Chromosome.

Tissue specificity. Ubiquitously expressed.

Post-translational modifications. Phosphorylation by CK2 disrupt the intramolecular binding between the bromo domain 2 and the NPS region and promotes binding between the NPS and the BID regions, leading to activate the protein and promote binding to acetylated histones. In absence of phosphorylation, BRD4 does not localize to p53/TP53 target gene promoters, phosphorylation promoting recruitment to p53/TP53 target promoters.

Disease relevance. Cornelia de Lange syndrome 6 (CDLS6) [MIM:620568] A form of Cornelia de Lange syndrome, a clinically heterogeneous developmental disorder associated with malformations affecting multiple systems. It is characterized by facial dysmorphisms, abnormal hands and feet, growth delay, cognitive retardation, hirsutism, gastroesophageal dysfunction and cardiac, ophthalmologic and genitourinary anomalies. CDLS6 inheritance is autosomal dominant. The disease is caused by variants affecting the gene represented in this entry. A chromosomal aberration involving BRD4 is found in a rare, aggressive, and lethal carcinoma arising in midline organs of young people. Translocation t(15;19)(q14;p13) with NUTM1 which produces a BRD4-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 NET domain mediates interaction with a number of chromatin proteins involved in transcription regulation (NSD3, JMJD6, CHD4, GLTSCR1 and ATAD5). The C-terminal (CTD) region mediates interaction and recruitment of CDK9 and CCNT1 subunits of the P-TEFb complex. It is also required for maintenance of higher-order chromatin structure. The 2 bromo domains mediate specific binding to acetylated histones via Asn-140 and Asn-433, respectively. The exact combination of modified histone tails required to recruit BRD4 to target genes is still unclear. The first bromo domain has high affinity for acetylated histone H4 tail, whereas the second bromo domain recognizes multiply acetylated marks in histone H3. A number of specific inhibitors bind competitively to acetyl-lysine-binding residues Asn-140 and Asn-433, promoting removal from acetylated histones. Many of these inhibitors are benzodiazepine derivatives. Does not contain the C-terminal (CTD) region required to recruit the P-TEFb complex.

Miscellaneous. Some specific inhibitors of BRD4 that prevent binding to acetylated histones by binding Asn-140 and Asn-433 are promising therapeutic molecules for the treatment of leukemias. JQ1, a thieno-triazolo-1,4-diazepine derivative, and I-BET, a benzodiazepine derivative, have been tested on tumors with success. Treatment with GSK1210151A (I-BET151, a I-BET derivative) has strong effets on mixed lineage leukemia and promotes myeloid differentiation and leukemia stem-cell depletion. 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).

Similarity. Belongs to the BET family.

Isoforms (3)

UniProt ID	Names	Canonical?
O60885-1	A, Brd4L, Long	yes
O60885-2	C, Brd4S, Short
O60885-3	B

RefSeq proteins (5): NP_001317313, NP_001366220, NP_001366221, NP_055114, NP_490597 (=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001487	Bromodomain	Domain
IPR018359	Bromodomain_CS	Conserved_site
IPR027353	NET_dom	Domain
IPR031354	BRD4_CDT	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, PF17105

UniProt features (119 total): compositionally biased region 25, helix 23, modified residue 14, sequence variant 11, region of interest 9, strand 9, cross-link 8, mutagenesis site 6, turn 4, domain 3, site 3, splice variant 3, chain 1

Structure

Experimental structures (PDB)

619 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
4QB3	X-RAY DIFFRACTION	0.94
6FO5	X-RAY DIFFRACTION	0.95
7Z9W	X-RAY DIFFRACTION	0.99
4ZC9	X-RAY DIFFRACTION	0.99
6I7Y	X-RAY DIFFRACTION	1
7ZAJ	X-RAY DIFFRACTION	1
8YMG	X-RAY DIFFRACTION	1.01
8YMI	X-RAY DIFFRACTION	1.01
8YMF	X-RAY DIFFRACTION	1.01
7Z9Y	X-RAY DIFFRACTION	1.04
7ZA8	X-RAY DIFFRACTION	1.04
7ZE6	X-RAY DIFFRACTION	1.04
8YMH	X-RAY DIFFRACTION	1.04
5EI4	X-RAY DIFFRACTION	1.05
6YQN	X-RAY DIFFRACTION	1.05
7RN2	X-RAY DIFFRACTION	1.05
7ZA9	X-RAY DIFFRACTION	1.05
4Z1S	X-RAY DIFFRACTION	1.06
7ZA7	X-RAY DIFFRACTION	1.06
6XUZ	X-RAY DIFFRACTION	1.07
6YQO	X-RAY DIFFRACTION	1.07
7ZAD	X-RAY DIFFRACTION	1.07
6ZED	X-RAY DIFFRACTION	1.08
7ZFZ	X-RAY DIFFRACTION	1.08
7ZFO	X-RAY DIFFRACTION	1.09
6XVC	X-RAY DIFFRACTION	1.1
6S25	X-RAY DIFFRACTION	1.1
7ZAE	X-RAY DIFFRACTION	1.1
8P9G	X-RAY DIFFRACTION	1.1
7ZAQ	X-RAY DIFFRACTION	1.11

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O60885-F1	56.20	0.19

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 (3): 140 (acetylated histone binding); 433 (acetylated histone binding); 719–720 (breakpoint for translocation to form bdr4-nutm1 fusion protein)

Post-translational modifications (22): 470, 484, 488, 492, 494, 498, 499, 503, 601, 1111, 1117, 1126, 1201, 1204, 99, 585, 645, 694, 1050, 1111 …

Mutagenesis-validated functional residues (6):

Position	Phenotype
140	abolishes binding to acetylated histones.
433	abolishes binding to acetylated histones.
492–494	impaired phosphorylation by ck2 and binding to acetylated histones.
498–500	impaired phosphorylation by ck2 and binding to acetylated histones.
503	impaired phosphorylation by ck2 and binding to acetylated histones.
651–653	decreases interaction with jmjd6 and nsd3. no effect on interaction with histone 4 acetylated.

Function

Pathways and Gene Ontology

Reactome pathways

6 pathways

ID	Pathway
R-HSA-9679191	Potential therapeutics for SARS
R-HSA-9909649	Regulation of PD-L1(CD274) transcription
R-HSA-1643685	Disease
R-HSA-5663205	Infectious disease
R-HSA-9679506	SARS-CoV Infections
R-HSA-9824446	Viral Infection Pathways

MSigDB gene sets: 681 (showing top): TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_REGULATION_OF_CELL_ACTIVATION, GOBP_REGULATION_OF_CELL_CYCLE_CHECKPOINT, GOBP_POSITIVE_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, WWTAAGGC_UNKNOWN, GOBP_REGULATION_OF_ALPHA_BETA_T_CELL_ACTIVATION, GOBP_POSITIVE_REGULATION_OF_HEMOPOIESIS, REACTOME_ADAPTIVE_IMMUNE_SYSTEM, GOBP_POSITIVE_REGULATION_OF_CELL_FATE_COMMITMENT, GOBP_INFLAMMATORY_RESPONSE, GOBP_T_CELL_ACTIVATION_INVOLVED_IN_IMMUNE_RESPONSE, GOBP_REGULATION_OF_ADAPTIVE_IMMUNE_RESPONSE, GCANCTGNY_MYOD_Q6, GOBP_ALPHA_BETA_T_CELL_DIFFERENTIATION, GOBP_CANONICAL_NF_KAPPAB_SIGNAL_TRANSDUCTION

GO Biological Process (14): chromatin remodeling (GO:0006338), regulation of transcription by RNA polymerase II (GO:0006357), DNA damage response (GO:0006974), positive regulation of G2/M transition of mitotic cell cycle (GO:0010971), positive regulation of transcription elongation by RNA polymerase II (GO:0032968), positive regulation of canonical NF-kappaB signal transduction (GO:0043123), host-mediated suppression of viral transcription (GO:0043922), positive regulation of DNA-templated transcription (GO:0045893), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of inflammatory response (GO:0050727), negative regulation of DNA damage checkpoint (GO:2000002), positive regulation of T-helper 17 cell lineage commitment (GO:2000330), chromatin organization (GO:0006325), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (20): transcription cis-regulatory region binding (GO:0000976), p53 binding (GO:0002039), chromatin binding (GO:0003682), transcription coregulator activity (GO:0003712), transcription coactivator activity (GO:0003713), protein serine/threonine kinase activity (GO:0004674), RNA polymerase II CTD heptapeptide repeat kinase activity (GO:0008353), enzyme binding (GO:0019899), histone binding (GO:0042393), RNA polymerase II C-terminal domain binding (GO:0099122), P-TEFb complex binding (GO:0106140), histone H4 reader activity (GO:0140008), histone H4K12ac reader activity (GO:0140011), histone H4K5ac reader activity (GO:0140012), histone H4K16ac reader activity (GO:0140046), histone H4K8ac reader activity (GO:0140055), histone H3K9ac reader activity (GO:0140072), histone H3K27ac reader activity (GO:0140119), protein binding (GO:0005515), protein-macromolecule adaptor activity (GO:0030674)

GO Cellular Component (5): chromatin (GO:0000785), condensed nuclear chromosome (GO:0000794), nucleus (GO:0005634), nucleoplasm (GO:0005654), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
SARS-CoV Infections	1
Regulation of PD-L1(CD274) expression	1
Disease	1
Viral Infection Pathways	1
Infectious disease	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
protein binding	4
histone H4 reader activity	4
regulation of DNA-templated transcription	2
transcription by RNA polymerase II	2
DNA-templated transcription	2
positive regulation of DNA-templated transcription	2
binding	2
histone H3 reader activity	2
cellular anatomical structure	2
chromatin organization	1
cellular response to stress	1
G2/M transition of mitotic cell cycle	1
regulation of G2/M transition of mitotic cell cycle	1
positive regulation of mitotic cell cycle phase transition	1
positive regulation of cell cycle G2/M phase transition	1
transcription elongation by RNA polymerase II	1
positive regulation of DNA-templated transcription, elongation	1
regulation of transcription elongation by RNA polymerase II	1
positive regulation of transcription by RNA polymerase II	1
canonical NF-kappaB signal transduction	1
regulation of canonical NF-kappaB signal transduction	1
positive regulation of intracellular signal transduction	1
host-mediated perturbation of viral transcription	1
host-mediated suppression of viral proces	1
positive regulation of RNA biosynthetic process	1
regulation of transcription by RNA polymerase II	1
inflammatory response	1
regulation of defense response	1
regulation of response to external stimulus	1
DNA damage checkpoint signaling	1
negative regulation of cell cycle checkpoint	1
regulation of DNA damage checkpoint	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
regulation of gene expression	1
regulation of RNA biosynthetic process	1
transcription regulatory region nucleic acid binding	1

Protein interactions and networks

STRING

5234 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
BRD4	CCNT1	O60563	999
BRD4	CDK9	P50750	999
BRD4	H4C16	P02304	993
BRD4	H4C7	Q99525	993
BRD4	H3-3A	P06351	990
BRD4	H3C1	P02295	990
BRD4	H3-4	Q16695	990
BRD4	H3-7	Q5TEC6	989
BRD4	H3-5	Q6NXT2	989
BRD4	H3C14	Q71DI3	989
BRD4	RELA	Q04206	986
BRD4	DEFB1	P60022	984
BRD4	NSD3	Q9BZ95	983
BRD4	NUTM1	Q86Y26	982
BRD4	JMJD6	Q6NYC1	979

IntAct

174 interactions, top by confidence:

A	B	Type	Score
BRD4	RELA	psi-mi:“MI:0915”(physical association)	0.810
BRD4	RELA	psi-mi:“MI:0407”(direct interaction)	0.810
BRD4	JMJD6	psi-mi:“MI:0915”(physical association)	0.780
BRD4	JMJD6	psi-mi:“MI:0407”(direct interaction)	0.780
JMJD6	BRD4	psi-mi:“MI:0915”(physical association)	0.780
JMJD6	BRD4	psi-mi:“MI:0407”(direct interaction)	0.780
BRD4	E2	psi-mi:“MI:0915”(physical association)	0.770
E2	BRD4	psi-mi:“MI:0915”(physical association)	0.770
FAM90A1	BRD4	psi-mi:“MI:2364”(proximity)	0.760
FAM90A1	BRD4	psi-mi:“MI:0915”(physical association)	0.760
FAM90A1	KPNA3	psi-mi:“MI:0914”(association)	0.670
	BRD4	psi-mi:“MI:0407”(direct interaction)	0.650
	BRD4	psi-mi:“MI:0914”(association)	0.650

BioGRID (2475): BRD4 (Affinity Capture-MS), BRD4 (Affinity Capture-MS), BRD4 (Affinity Capture-MS), BRD4 (Affinity Capture-Western), WHSC1L1 (Affinity Capture-Western), BRD3 (Co-fractionation), BRD4 (Co-fractionation), BRD4 (Co-fractionation), BRD4 (Co-fractionation), DMAP1 (Co-fractionation), RTF1 (Co-fractionation), ZC3H18 (Co-fractionation), BRD4 (Affinity Capture-MS), BRD4 (Affinity Capture-MS), BRD4 (Affinity Capture-Western)

ESM2 similar proteins: A1ZA47, B6RSP1, O14964, O17583, O35625, O42400, O54916, O60885, O74252, O75553, P0C090, P15330, P16554, P49757, P57094, P97318, P98078, Q0V8S0, Q21502, Q24212, Q24478, Q2LC84, Q5F464, Q5TYQ8, Q5XI07, Q62415, Q641G3, Q69ZW3, Q6DFF2, Q6NUC6, Q75BK1, Q8BG30, Q8CJH2, Q8IPJ3, Q8NDI1, Q96D71, Q96KQ4, Q9BGX5, Q9H3P2, Q9HBD1

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

20 interactions.

A	Effect	B	Mechanism
BRD4	up-regulates	POLR2A	phosphorylation
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”	BRD4	“chemical inhibition”
“CID 122201421”	“down-regulates activity”	BRD4	“chemical inhibition”
“CPI-0610 carboxylic acid”	“down-regulates activity”	BRD4	“chemical inhibition”
“CID 132010322”	“down-regulates activity”	BRD4	“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”	BRD4	“chemical inhibition”
BRD4	“down-regulates quantity by destabilization”	MYC	phosphorylation
MYC	“down-regulates activity”	BRD4
MAPK3	“down-regulates activity”	BRD4
BRD4	“up-regulates activity”	EP300	binding
H4C1	“up-regulates activity”	BRD4	relocalization
BRD4	“up-regulates quantity by expression”	KDM5C	“transcriptional regulation”
BRD4	“up-regulates activity”	P-TEFb	binding
ATAD5	up-regulates	BRD4	binding
ASXL3	“up-regulates activity”	BRD4	binding
JAK2	“up-regulates quantity by stabilization”	BRD4	phosphorylation
JQ1	“down-regulates activity”	BRD4	“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”	BRD4	“chemical inhibition”
YAP/TAZ	“up-regulates activity”	BRD4	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 121 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
Downstream signal transduction	5	23.2×	2e-03
Interleukin-7 signaling	5	19.3×	2e-03
RHOU GTPase cycle	5	17.0×	2e-03
Synthesis of PIPs at the plasma membrane	5	12.9×	4e-03
Extra-nuclear estrogen signaling	5	10.4×	5e-03
Signaling by ALK fusions and activated point mutants	5	9.2×	7e-03
PKR-mediated signaling	5	8.6×	8e-03
VEGFA-VEGFR2 Pathway	5	8.5×	8e-03

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of miRNA transcription	6	16.9×	2e-03

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: activating (oncogene-like) across 4 cancer types — BLCA, HNSC, PRAD, RCC.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	16
Likely pathogenic	18
Uncertain significance	413
Likely benign	394
Benign	73

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1685591	NM_001379291.1(BRD4):c.4020+1G>A	Pathogenic
1708222	NM_001379291.1(BRD4):c.3693_3709dup (p.Arg1237fs)	Pathogenic
1708497	NM_001379291.1(BRD4):c.2239C>T (p.Gln747Ter)	Pathogenic
2093082	NM_001379291.1(BRD4):c.3540_3541del (p.Lys1181fs)	Pathogenic
2427174	NC_000019.9:g.(?15366088)(15368004_?)del	Pathogenic
2671881	NM_001379291.1(BRD4):c.1224delinsCA (p.Glu408fs)	Pathogenic
2671882	NM_001379291.1(BRD4):c.2753_2754insT (p.Pro919fs)	Pathogenic
2715337	NM_001379291.1(BRD4):c.1807G>T (p.Glu603Ter)	Pathogenic
3242728	NC_000019.9:g.(?15379191)(15386256_?)del	Pathogenic
3342841	NM_001379291.1(BRD4):c.137dup (p.Pro47fs)	Pathogenic
3482296	NM_001379291.1(BRD4):c.1393_1420delinsCAA (p.Val465fs)	Pathogenic
4538455	NM_001379291.1(BRD4):c.1552-1G>A	Pathogenic
4720325	NM_001379291.1(BRD4):c.555_558del (p.Thr186fs)	Pathogenic
4820175	NM_001379291.1(BRD4):c.285+1G>T	Pathogenic
504087	NM_001379291.1(BRD4):c.766dup (p.Gln256fs)	Pathogenic
847436	NM_001379291.1(BRD4):c.358_367del (p.Trp120fs)	Pathogenic
1700687	NM_001379291.1(BRD4):c.3666_3672dup (p.Glu1225fs)	Likely pathogenic
2431678	NM_001379291.1(BRD4):c.3282+2T>C	Likely pathogenic
2443328	NM_001379291.1(BRD4):c.1289A>G (p.Tyr430Cys)	Likely pathogenic
2577936	NM_001379291.1(BRD4):c.1960del (p.Ile654fs)	Likely pathogenic
2864923	NM_001379291.1(BRD4):c.338G>T (p.Arg113Leu)	Likely pathogenic
2920692	NM_001379291.1(BRD4):c.3312_3319del (p.Gln1105fs)	Likely pathogenic
2920709	NM_001379291.1(BRD4):c.2728dup (p.Gln910fs)	Likely pathogenic
3062000	NM_001379291.1(BRD4):c.703C>T (p.Gln235Ter)	Likely pathogenic
3629461	NM_001379291.1(BRD4):c.1698_1701dup (p.Pro568fs)	Likely pathogenic
3771157	NM_001379291.1(BRD4):c.2872dup (p.Leu958fs)	Likely pathogenic
3775476	NM_001379291.1(BRD4):c.394_395del (p.Met132fs)	Likely pathogenic
4072313	NM_001379291.1(BRD4):c.3510del (p.Pro1171fs)	Likely pathogenic
4293038	NM_001379291.1(BRD4):c.1315dup (p.Val439fs)	Likely pathogenic
4755534	NM_001379291.1(BRD4):c.3710_3719del (p.Arg1237fs)	Likely pathogenic

SpliceAI

3927 predictions. Top by Δscore:

Variant	Effect	Δscore
19:15238741:A:AC	donor_gain	1.0000
19:15238742:C:CT	donor_gain	1.0000
19:15238742:CGG:C	donor_gain	1.0000
19:15238747:T:TA	donor_gain	1.0000
19:15238748:C:A	donor_gain	1.0000
19:15238978:CTC:C	acceptor_gain	1.0000
19:15238980:CCT:C	acceptor_loss	1.0000
19:15238981:C:CC	acceptor_gain	1.0000
19:15239054:CCCA:C	donor_loss	1.0000
19:15239056:CACC:C	donor_loss	1.0000
19:15239060:T:TA	donor_gain	1.0000
19:15239068:T:TA	donor_gain	1.0000
19:15239072:G:A	donor_gain	1.0000
19:15239083:T:A	donor_gain	1.0000
19:15239089:T:TA	donor_gain	1.0000
19:15239260:AGGTC:A	acceptor_gain	1.0000
19:15239261:GGTC:G	acceptor_gain	1.0000
19:15239262:GTC:G	acceptor_gain	1.0000
19:15239262:GTCC:G	acceptor_loss	1.0000
19:15239263:TC:T	acceptor_gain	1.0000
19:15239264:CC:C	acceptor_gain	1.0000
19:15239265:C:CC	acceptor_gain	1.0000
19:15239405:A:C	donor_gain	1.0000
19:15239420:T:TA	donor_gain	1.0000
19:15239518:CGGCC:C	acceptor_gain	1.0000
19:15239521:CC:C	acceptor_gain	1.0000
19:15239522:CC:C	acceptor_gain	1.0000
19:15239523:C:CC	acceptor_gain	1.0000
19:15239655:TCA:T	donor_loss	1.0000
19:15239656:CA:C	donor_loss	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000002445 (19:15300138 T>C), RS1000017091 (19:15334136 G>A,C), RS1000017825 (19:15257658 C>A,T), RS1000040567 (19:15240891 G>A), RS1000106340 (19:15330540 T>A,C), RS1000109014 (19:15294617 C>A), RS1000109443 (19:15300389 TAA>T,TA,TAAA,TAAAA), RS1000123108 (19:15256604 G>A,C), RS1000126670 (19:15263356 A>C,G), RS1000129071 (19:15276268 C>T), RS1000166241 (19:15243728 A>C,G), RS1000249681 (19:15315166 C>A), RS1000268623 (19:15284412 T>C), RS1000275670 (19:15249537 C>A,G,T), RS1000298968 (19:15259051 G>A,C)

Disease associations

OMIM: gene MIM:608749 | disease phenotypes: MIM:122470, MIM:620568

GenCC curated gene-disease

Disease	Classification	Inheritance
Cornelia de Lange syndrome 6	Strong	Autosomal dominant
Cornelia de Lange syndrome	Supportive	Autosomal dominant
multiple congenital anomalies/dysmorphic syndrome	Limited	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
syndromic intellectual disability	Definitive	AD

Mondo (8): neurodevelopmental disorder (MONDO:0700092), Cornelia de Lange syndrome (MONDO:0016033), syndromic intellectual disability (MONDO:0000508), intellectual disability (MONDO:0001071), Cornelia de Lange syndrome 6 (MONDO:0957921), Cornelia de Lange syndrome 1 (MONDO:0007387), mental disorder (MONDO:0005084), multiple congenital anomalies/dysmorphic syndrome (MONDO:0019042)

Orphanet (3): Cornelia de Lange syndrome (Orphanet:199), Rare genetic syndromic intellectual disability (Orphanet:183763), NON RARE IN EUROPE: Unexplained intellectual disability (Orphanet:319658)

HPO phenotypes

136 total (30 of 136 shown, HPO-id order):

HPO	Term
HP:0000003	Multicystic kidney dysplasia
HP:0000006	Autosomal dominant inheritance
HP:0000023	Inguinal hernia
HP:0000028	Cryptorchidism
HP:0000047	Hypospadias
HP:0000059	Hypoplastic labia majora
HP:0000076	Vesicoureteral reflux
HP:0000083	Renal insufficiency
HP:0000130	Abnormality of the uterus
HP:0000175	Cleft palate
HP:0000218	High palate
HP:0000233	Thin vermilion border
HP:0000248	Brachycephaly
HP:0000252	Microcephaly
HP:0000294	Low anterior hairline
HP:0000316	Hypertelorism
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000405	Conductive hearing impairment
HP:0000407	Sensorineural hearing impairment
HP:0000413	Atresia of the external auditory canal
HP:0000453	Choanal atresia
HP:0000463	Anteverted nares
HP:0000470	Short neck
HP:0000482	Microcornea
HP:0000486	Strabismus
HP:0000494	Downslanted palpebral fissures

GWAS associations

5 associations (top):

Study	Trait	p-value
GCST007267_154	Systolic blood pressure	5.000000e-09
GCST90002387_47	Immature fraction of reticulocytes	7.000000e-13
GCST90002396_23	Mean reticulocyte volume	3.000000e-13
GCST90002402_618	Platelet count	5.000000e-12
GCST90002404_566	Red cell distribution width	1.000000e-13

EFO canonical traits (4, from GWAS)

EFO ID	Trait name
EFO:0006335	systolic blood pressure
EFO:0010701	mean reticulocyte volume
EFO:0004309	platelet count
EFO:0009188	Red cell distribution width

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D008607	Intellectual Disability	C10.597.606.360; C23.888.592.604.646; F01.700.687; F03.625.539
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (23): CHEMBL1163125 (SINGLE PROTEIN), CHEMBL4106143 (PROTEIN COMPLEX), CHEMBL4296133 (PROTEIN-PROTEIN INTERACTION), CHEMBL4296138 (PROTEIN-PROTEIN INTERACTION), CHEMBL4296140 (PROTEIN-PROTEIN INTERACTION), CHEMBL4296145 (PROTEIN-PROTEIN INTERACTION), CHEMBL4296148 (PROTEIN-PROTEIN INTERACTION), CHEMBL4296614 (PROTEIN FAMILY), CHEMBL4523719 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523722 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

31 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 449,213 (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
CHEMBL112	ACETAMINOPHEN	4	157,242
CHEMBL1287853	FEDRATINIB	4	3,554
CHEMBL1454910	NITROXOLINE	4	1,860
CHEMBL343448	ROMIDEPSIN	4	12,963
CHEMBL408513	BELINOSTAT	4	7,765
CHEMBL483254	PANOBINOSTAT	4	11,666
CHEMBL661	ALPRAZOLAM	4	130,677
CHEMBL848	LENALIDOMIDE	4	5,256
CHEMBL9	NORFLOXACIN	4	46,757
CHEMBL98	VORINOSTAT	4	50,361
CHEMBL1233528	VOLASERTIB	3	1,511
CHEMBL2103840	DINACICLIB	3	2,257
CHEMBL235191	TACEDINALINE	3	2,950
CHEMBL2393130	APABETALONE	3	1,350
CHEMBL4303404	PELABRESIB	3	1,513
CHEMBL1232461	MOLIBRESIB	2	1,538
CHEMBL225164	CLOXYQUIN	2	3,892
CHEMBL2326966	SF-1126	2	4,243
CHEMBL3581647	BIRABRESIB	2	1,546
CHEMBL3919831	AMREDOBRESIB	2	312
CHEMBL3982690	ALOBRESIB	2
CHEMBL3987016	MIVEBRESIB	2
CHEMBL4297458	EZOBRESIB	2
CHEMBL513909	BI-2536	2
CHEMBL837	7-ETHYL-10-HYDROXYCAMPTOTHECIN	2
CHEMBL12543	METHYLPYRROLIDONE	1
CHEMBL4078100	AZD-5153	1
CHEMBL4297423	RO-6870810	1
CHEMBL4297454	ABBV-744	1
CHEMBL4521078	PLX-51107	1

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Bromodomain kinase (BRDK) family

Most potent curated ligand interactions (45 total), top 25:

Ligand	Action	Affinity	Parameter
compound 25ap [PMID: 37796543]	Inhibition	9.03	pIC50
BMS-986158	Inhibition	8.96	pIC50
mivebresib	Inhibition	8.85	pKi
NHWD-870	Inhibition	8.57	pIC50
zavabresib	Inhibition	8.37	pIC50
ARV-771	Inhibition	8.12	pKd
repibresib	Binding	8.0	pKd
dBET6	Inhibition	7.85	pIC50
GW841819X	Inhibition	7.81	pIC50
MZ1	Binding	7.59	pKd
isoxazole azepine compound 3	Inhibition	7.59	pIC50
compound 11h [PMID: 29808961]	Inhibition	7.57	pIC50
dual BRD4/PLK1 inhibitor 23	Inhibition	7.55	pIC50
MS436	Inhibition	7.52	pKi
MS417	Inhibition	7.52	pIC50
BI-2536	Inhibition	7.43	pKd
CPI-203	Inhibition	7.43	pIC50
pelabresib	Inhibition	7.41	pIC50
I-BET282	Inhibition	7.4	pIC50
apabetalone	Antagonist	7.4	pIC50
(+)-JQ1	Inhibition	7.3	pKd
compound 3 [PMID: 25408830]	Inhibition	7.1	pIC50
amredobresib	Inhibition	7.05	pIC50
WNY0824	Inhibition	6.96	pIC50
XD14	Inhibition	6.8	pKd

Binding affinities (BindingDB)

2976 measured of 5117 human assays (5252 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
US10407441, Compound JQ6	IC50	0.24 nM	US-9320741: Compositions and methods for treating neoplasia, inflammatory disease and other disorders
N-[3-(6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl)-4-phenoxyphenyl]ethanesulfonamide	KI	0.25 nM	US-9296741: Bromodomain inhibitors
2-[10-(3,5-dimethyltriazol-4-yl)-7-[(S)-(3-fluoro-2-pyridinyl)-(oxan-4-yl)methyl]-3,4,7,12-tetrazatricyclo[6.4.0.02,6]dodecan-5-yl]propan-2-ol	IC50	0.4 nM	US-11466005: Tricyclic compounds
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-(1H-imidazol-5-yl)ethyl]acetamide	IC50	0.427 nM	US-9320741: Compositions and methods for treating neoplasia, inflammatory disease and other disorders
4-(2-cyclohexyloxy-5-methylsulfonylphenyl)-6-methyl-1H-pyrrolo[2,3-c]pyridin-7-one	KI	0.46 nM	US-9296741: Bromodomain inhibitors
4-[5-(methanesulfonamido)-2-phenoxyphenyl]-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridine-2-carboxamide	KI	0.5 nM	US-9296741: Bromodomain inhibitors
2,2,2-trifluoro-N-[3-(6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl)-4-(oxan-3-yloxy)phenyl]ethanesulfonamide	KI	0.5 nM	US-9296741: Bromodomain inhibitors
4-[5-[(1,1-dioxo-1,2-thiazolidin-2-yl)methyl]-2-phenoxyphenyl]-6-methyl-1H-pyrrolo[2,3-c]pyridin-7-one	KI	0.51 nM	US-9296741: Bromodomain inhibitors
N-[3-(6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl)-4-(oxan-3-yloxy)phenyl]ethanesulfonamide	KI	0.52 nM	US-9296741: Bromodomain inhibitors
4-[5-ethylsulfonyl-2-(4-methoxy-4-methylcyclohexyl)oxyphenyl]-6-methyl-1H-pyrrolo[2,3-c]pyridin-7-one	KI	0.57 nM	US-9296741: Bromodomain inhibitors
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-(4-methylpiperazin-1-yl)ethyl]acetamide	IC50	0.584 nM	US-9320741: Compositions and methods for treating neoplasia, inflammatory disease and other disorders
N-[4-[[3-[2-(6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl)-4-methylsulfonylphenoxy]anilino]methyl]phenyl]acetamide	KI	0.6 nM	US-9957263: Bromodomain inhibitors
N-[4-(2,6-difluorophenoxy)-3-[2-(3-methoxyprop-1-ynyl)-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl]phenyl]ethanesulfonamide	KI	0.605 nM	US-9957263: Bromodomain inhibitors
4-[4-(ethylsulfonylamino)-2-(6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl)phenoxy]benzamide	KI	0.65 nM	US-9296741: Bromodomain inhibitors
4-(2-cyclohexyloxy-5-ethylsulfonylphenyl)-6-methyl-2-(1-piperidin-4-ylpyrazol-4-yl)-1H-pyrrolo[2,3-c]pyridin-7-one	KI	0.669 nM	US-9957263: Bromodomain inhibitors
4-[5-(hydroxymethyl)-2-phenoxyphenyl]-6-methyl-1H-pyrrolo[2,3-c]pyridin-7-one	KI	0.68 nM	US-9296741: Bromodomain inhibitors
N-[3-(6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl)-4-(oxolan-3-yloxy)phenyl]ethanesulfonamide	KI	0.74 nM	US-9296741: Bromodomain inhibitors
N-[5-(6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl)-6-phenoxy-3-pyridinyl]methanesulfonamide	KI	0.75 nM	US-9296741: Bromodomain inhibitors
N-[3-(6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl)-4-(oxan-3-yloxy)phenyl]methanesulfonamide	KI	0.75 nM	US-9296741: Bromodomain inhibitors
4-[5-ethylsulfonyl-2-(4-hydroxycyclohexyl)oxyphenyl]-6-methyl-1H-pyrrolo[2,3-c]pyridin-7-one	KI	0.75 nM	US-9296741: Bromodomain inhibitors
4-(cyclopropylmethylamino)-3-(6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl)benzenesulfonamide	KI	0.78 nM	US-9296741: Bromodomain inhibitors
4-[2-(1,4-dioxaspiro[4.5]decan-8-yloxy)-5-ethylsulfonylphenyl]-6-methyl-1H-pyrrolo[2,3-c]pyridin-7-one	KI	0.79 nM	US-9296741: Bromodomain inhibitors
5-(2,4-difluorophenoxy)-2-(ethylsulfonylamino)-4-(6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl)benzoic acid	KI	0.8 nM	US-9957263: Bromodomain inhibitors
4-(cyclopropylmethoxy)-3-(6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl)benzenesulfonamide	KI	0.83 nM	US-9296741: Bromodomain inhibitors
4-[2-(4,4-difluorocyclohexyl)oxy-5-ethylsulfonylphenyl]-6-methyl-1H-pyrrolo[2,3-c]pyridin-7-one	KI	0.86 nM	US-9296741: Bromodomain inhibitors
(6S+2S)-PEG3 (9)	IC50	0.878 nM
US9296741, 81	KI	0.99 nM	US-9296741: Bromodomain inhibitors
6-[1-[(5-fluoro-2-pyridinyl)methyl]-6-morpholin-4-ylimidazo[4,5-c]pyridin-2-yl]-3-methyl-N-propan-2-yl-[1,2,4]triazolo[4,3-a]pyrazin-8-amine	IC50	1 nM	US-9266891: Substituted [1,2,4]triazolo[4,3-A]pyrazines that are BRD4 inhibitors
4-[5-(dimethylsulfamoylamino)-2-phenoxyphenyl]-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridine	KI	1 nM	US-9296741: Bromodomain inhibitors
N-[3-[4-methylsulfonyl-2-(7-oxo-6,7a-dihydropyrrolo[2,3-c]pyridin-4-yl)phenoxy]phenyl]cyclopropanesulfonamide	KI	1 nM	US-9957263: Bromodomain inhibitors
3,4-dimethoxy-N-[3-[2-(6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl)-4-methylsulfonylphenoxy]phenyl]benzenesulfonamide	KI	1 nM	US-9957263: Bromodomain inhibitors
3-[5-[(5S)-3-cyclopropyl-5,7-dimethyl-6-oxo-5,8-dihydroimidazo[1,5-a]pyrazin-1-yl]-3-(difluoromethyl)quinolin-2-yl]-1,2,4-oxadiazolidin-5-one	IC50	1 nM	US-10899769: Imidazopiperazinone inhibitors of transcription activating proteins
3-[8-[(5S)-3-cyclopropyl-5,7-dimethyl-6-oxo-5,8-dihydroimidazo[1,5-a]pyrazin-1-yl]isoquinolin-3-yl]-1,2,4-oxadiazolidin-5-one	IC50	1 nM	US-10899769: Imidazopiperazinone inhibitors of transcription activating proteins
(6S+2S)-PEG4 (10)	IC50	1.09 nM
N-ethyl-4-[5-(methanesulfonamido)-2-phenoxyphenyl]-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridine-2-carboxamide	KI	1.1 nM	US-9296741: Bromodomain inhibitors
3-(6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl)-4-phenoxybenzenesulfonamide	KI	1.1 nM	US-9296741: Bromodomain inhibitors
6-(cyclohexylamino)-5-(6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl)pyridine-3-sulfonamide	KI	1.1 nM	US-9296741: Bromodomain inhibitors
4-[2-(cyclohexylamino)-5-methylsulfonylphenyl]-6-methyl-1H-pyrrolo[2,3-c]pyridin-7-one	KI	1.1 nM	US-9296741: Bromodomain inhibitors
4-[2-(cyclopropylmethylamino)-5-ethylsulfonylphenyl]-6-methyl-1H-pyrrolo[2,3-c]pyridin-7-one	KI	1.1 nM	US-9296741: Bromodomain inhibitors
4-fluoro-2-methyl-N-[3-[2-(6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl)-4-methylsulfonylphenoxy]phenyl]benzenesulfonamide	KI	1.1 nM	US-9957263: Bromodomain inhibitors
N-[3-[2-(6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl)-4-methylsulfonylphenoxy]phenyl]-4-methylsulfonylbenzenesulfonamide	KI	1.1 nM	US-9957263: Bromodomain inhibitors
4-[2-[3-(2,3-dihydro-1,4-benzodioxin-6-ylmethylamino)phenoxy]-5-methylsulfonylphenyl]-6-methyl-1H-pyrrolo[2,3-c]pyridin-7-one	KI	1.1 nM	US-9957263: Bromodomain inhibitors
6-methyl-4-[5-methylsulfonyl-2-[[4-(naphthalen-2-ylmethylamino)cyclohexyl]amino]phenyl]-1H-pyrrolo[2,3-c]pyridin-7-one	KI	1.1 nM	US-9957263: Bromodomain inhibitors
(2S+2S)-PEG1 (5)	IC50	1.17 nM
4-[2-(2,4-difluorophenoxy)-5-(1,1-dioxo-1,2-thiazolidin-2-yl)phenyl]-6-methyl-1H-pyrrolo[2,3-c]pyridin-7-one	KI	1.2 nM	US-9296741: Bromodomain inhibitors
ethyl 4-[5-(methanesulfonamido)-2-phenoxyphenyl]-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridine-2-carboxylate	KI	1.2 nM	US-9296741: Bromodomain inhibitors
4-(2-cycloheptyloxy-5-methylsulfonylphenyl)-6-methyl-1H-pyrrolo[2,3-c]pyridin-7-one	KI	1.2 nM	US-9296741: Bromodomain inhibitors
4-[2-(2,4-difluorophenoxy)-5-methylsulfonylphenyl]-N-ethyl-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridine-2-carboxamide	KI	1.2 nM	US-9296741: Bromodomain inhibitors

ChEMBL bioactivities

6100 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
10.66	EC50	0.022	nM	CHEMBL5414378
10.02	Kd	0.095	nM	CHEMBL5170488
10.00	Kd	0.1	nM	CHEMBL4648912
10.00	IC50	0.1	nM	CHEMBL5424952
9.82	EC50	0.15	nM	CHEMBL5436180
9.70	IC50	0.2	nM	CHEMBL5440537
9.70	IC50	0.2	nM	CHEMBL5432745
9.62	IC50	0.24	nM	CHEMBL3895096
9.60	Ki	0.25	nM	CHEMBL3898684
9.54	Kd	0.29	nM	CHEMBL4648912
9.54	Kd	0.29	nM	CHEMBL5170488
9.52	Kd	0.3	nM	CHEMBL3770724
9.52	IC50	0.3	nM	CHEMBL5401253
9.52	IC50	0.3	nM	CHEMBL5440963
9.52	IC50	0.3	nM	CHEMBL5914594
9.50	IC50	0.3162	nM	CHEMBL5426022
9.49	Kd	0.32	nM	CHEMBL5170488
9.48	Kd	0.33	nM	CHEMBL4648912
9.48	IC50	0.33	nM	CHEMBL5171062
9.47	IC50	0.34	nM	CHEMBL5206375
9.47	IC50	0.34	nM	CHEMBL5980250
9.46	IC50	0.35	nM	CHEMBL5927816
9.41	Ki	0.39	nM	CHEMBL3898684
9.41	IC50	0.39	nM	CHEMBL5171510
9.40	IC50	0.3981	nM	CHEMBL2177300
9.40	IC50	0.4	nM	CHEMBL5091333
9.40	IC50	0.4	nM	CHEMBL5209870
9.40	IC50	0.4	nM	CHEMBL5422881
9.40	Ki	0.4	nM	CHEMBL6023722
9.40	IC50	0.4	nM	CHEMBL5954599
9.40	IC50	0.4	nM	CHEMBL5952972
9.40	IC50	0.4	nM	CHEMBL6034928
9.39	IC50	0.41	nM	CHEMBL5171031
9.38	IC50	0.42	nM	CHEMBL5269983
9.37	IC50	0.427	nM	CHEMBL3932024
9.37	Kd	0.43	nM	CHEMBL4077038
9.37	IC50	0.43	nM	CHEMBL4077038
9.37	IC50	0.43	nM	CHEMBL5176955
9.35	IC50	0.45	nM	CHEMBL5177436
9.34	Ki	0.46	nM	CHEMBL3979505
9.34	IC50	0.46	nM	CHEMBL5192071
9.32	IC50	0.48	nM	CHEMBL6018004
9.31	IC50	0.49	nM	CHEMBL5176955
9.31	IC50	0.49	nM	CHEMBL5175082
9.31	IC50	0.49	nM	CHEMBL6051531
9.30	Ki	0.5	nM	CHEMBL3926639
9.30	Ki	0.5	nM	CHEMBL3969291
9.30	Ki	0.5	nM	CHEMBL4166630
9.30	Ki	0.5	nM	CHEMBL4228445
9.30	Ki	0.5	nM	CHEMBL4435166

PubChem BioAssay actives

3153 with measured affinity, of 6100 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-[(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]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	1802214: BROMOscan Assay from Article 10.1038/nchembio.2209: “Design and characterization of bivalent BET inhibitors.”	kd	<0.0001	uM
methyl 2-[(9S)-7-(4-chlorophenyl)-4-[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]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	1802214: BROMOscan Assay from Article 10.1038/nchembio.2209: “Design and characterization of bivalent BET inhibitors.”	kd	<0.0001	uM
methyl 2-[(9S)-7-(4-chlorophenyl)-4-[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]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	1802214: BROMOscan Assay from Article 10.1038/nchembio.2209: “Design and characterization of bivalent BET inhibitors.”	kd	<0.0001	uM
methyl 2-[(9S)-7-(4-chlorophenyl)-4-[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]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	1802214: BROMOscan Assay from Article 10.1038/nchembio.2209: “Design and characterization of bivalent BET inhibitors.”	kd	<0.0001	uM
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	1802214: BROMOscan Assay from Article 10.1038/nchembio.2209: “Design and characterization of bivalent BET inhibitors.”	kd	<0.0001	uM
methyl 2-[(9S)-7-(4-chlorophenyl)-4-[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]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	1802214: BROMOscan Assay from Article 10.1038/nchembio.2209: “Design and characterization of bivalent BET inhibitors.”	kd	<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-[2-[2-[2-[[2-[7-(3,5-dimethyl-1,2-oxazol-4-yl)-8-methoxy-2-oxo-1-[(1R)-1-pyridin-2-ylethyl]imidazo[4,5-c]quinolin-3-yl]acetyl]amino]ethoxy]ethoxy]ethyl]acetamide	1802214: BROMOscan Assay from Article 10.1038/nchembio.2209: “Design and characterization of bivalent BET inhibitors.”	kd	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
N-[1-(1,1-dipyridin-2-ylethyl)-6-(1-methyl-7-oxo-6H-pyrrolo[2,3-c]pyridin-3-yl)indol-4-yl]ethanesulfonamide	1652242: Binding affinity to human full-length BRD4 short isoform (M1 to A722 residues) expressed in bacterial expression system by BROMOscan assay	kd	0.0001	uM
6-hydroxyhexyl 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	1460623: Inhibition of biotin-labeled acetylated peptide binding to BRD4 bromodomain 1 (unknown origin) expressed in Escherichia coli BL21 after 1 hr by BROMOscan assay	kd	0.0004	uM
methyl 4-[[(2S,4R)-6-(3-acetamidophenyl)-1-acetyl-2-methyl-3,4-dihydro-2H-quinolin-4-yl]amino]benzoate	1924026: Inhibition of poly His-tagged BRD4 BD2 (unknown origin) (348 to 455 residues) by BROMOscan assay	ic50	0.0004	uM
2-[8-fluoro-7-[3-methyl-5-(trideuteriomethyl)triazol-4-yl]-5-[(S)-oxan-4-yl(phenyl)methyl]pyrido[3,2-b]indol-3-yl]propan-2-ol	1807576: Inhibition of BRD4 (unknown origin)	ic50	0.0004	uM
7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-2-methyl-N-(5-methyl-2-propan-2-ylpyrazol-3-yl)-9H-pyrimido[4,5-b]indol-4-amine	1356095: Inhibition of FAM-labeled ZBA248 binding to recombinant human BRD4 bromodomain 1 (44 to 168 residues) expressed in Rosetta2 Escherichia coli DE3 cells after 30 mins by fluorescence polarization assay	ki	0.0005	uM
2-[7-(2,6-difluorophenyl)-9-methoxy-2-methyl-3-oxo-5H-pyrido[4,3-d][2]benzazepin-5-yl]-N-ethylacetamide	1460625: Inhibition of BRD4 bromodomain 1 (unknown origin) using biotinylated substrate after 1 hr by AlphaLisa assay	ic50	0.0005	uM
N-cyclopropyl-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	1548944: Inhibition of human N-terminal His6 tagged BRD4 BD2 (352 to 457) residues expressed in Escherichia coli BL21(DE3) cells after 1 hr by TR-FRET assay	ki	0.0005	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	1387717: Inhibition of FAM-labeled ZBA248 binding to recombinant N-terminal His6-tagged BRD4 bromodomain 1 (44 to 168 residues) (unknown origin) expressed in Escherichia coli Rosetta2 DE3 after 30 mins by fluorescence polarization assay	ki	0.0005	uM
4-[4-(5-fluoro-1H-indol-3-yl)-6-methoxy-9H-pyrimido[4,5-b]indol-7-yl]-3,5-dimethyl-1,2-oxazole	1371243: Inhibition of FAM-labeled ZBA248 binding to recombinant human N-terminal His6-tagged BRD4 bromodomain 1 (44 to 168 residues) expressed in Rosetta2 DE3 cells after 30 mins by Flourescence polarization assay	ki	0.0005	uM
4-[4-(5-fluoro-2-methyl-1H-indol-3-yl)-6-methoxy-9H-pyrimido[4,5-b]indol-7-yl]-3,5-dimethyl-1,2-oxazole	1371243: Inhibition of FAM-labeled ZBA248 binding to recombinant human N-terminal His6-tagged BRD4 bromodomain 1 (44 to 168 residues) expressed in Rosetta2 DE3 cells after 30 mins by Flourescence polarization assay	ki	0.0005	uM
4-[5-acetamido-2-(2,6-dimethylphenoxy)phenyl]-N-ethyl-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridine-2-carboxamide	1548944: Inhibition of human N-terminal His6 tagged BRD4 BD2 (352 to 457) residues expressed in Escherichia coli BL21(DE3) cells after 1 hr by TR-FRET assay	ki	0.0005	uM
N-ethyl-4-[5-ethylsulfonyl-2-(7-methyl-2,3-dihydroindol-1-yl)phenyl]-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridine-2-carboxamide	1548944: Inhibition of human N-terminal His6 tagged BRD4 BD2 (352 to 457) residues expressed in Escherichia coli BL21(DE3) cells after 1 hr by TR-FRET assay	ki	0.0005	uM
4-[2-(2-chlorophenoxy)-5-ethylsulfonylphenyl]-N-ethyl-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridine-2-carboxamide	1548944: Inhibition of human N-terminal His6 tagged BRD4 BD2 (352 to 457) residues expressed in Escherichia coli BL21(DE3) cells after 1 hr by TR-FRET assay	ki	0.0005	uM
N-[4-[[3-[2-(6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridin-4-yl)-4-methylsulfonylphenoxy]anilino]methyl]phenyl]acetamide	1460646: Inhibition of His-tagged BRD4 bromodomain 2 (E352 to E168 residues) (unknown origin) after 1 hr by TR-FRET assay	ki	0.0006	uM
2-[7-(3,5-dimethyltriazol-4-yl)-5-[(S)-oxan-4-yl(phenyl)methyl]pyrido[3,2-b]indol-3-yl]propan-2-ol	1807576: Inhibition of BRD4 (unknown origin)	ic50	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	1905948: Inhibition of C-terminal His6-tagged BRD4 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	0.0006	uM
4-[2-(2,6-dimethylphenoxy)-5-(2-hydroxypropan-2-yl)phenyl]-N-ethyl-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridine-2-carboxamide	1548944: Inhibition of human N-terminal His6 tagged BRD4 BD2 (352 to 457) residues expressed in Escherichia coli BL21(DE3) cells after 1 hr by TR-FRET assay	ki	0.0006	uM
4-[2-(methoxymethyl)-1-[(1R)-1-phenylethyl]-8-[[(3S)-pyrrolidin-3-yl]methoxy]imidazo[4,5-c]quinolin-7-yl]-3,5-dimethyl-1,2-oxazole	1814816: Binding affinity to human partial length BRD4 BD2 expressed in bacterial expression system assessed as dissociation constant by BROMOscan assay	kd	0.0006	uM
4-[5-cyclopropylsulfonyl-2-(2,6-dimethylphenoxy)phenyl]-N-ethyl-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridine-2-carboxamide	1548944: Inhibition of human N-terminal His6 tagged BRD4 BD2 (352 to 457) residues expressed in Escherichia coli BL21(DE3) cells after 1 hr by TR-FRET assay	ki	0.0006	uM
7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-2-methyl-N-(1-methylindazol-3-yl)-9H-pyrimido[4,5-b]indol-4-amine	1356095: Inhibition of FAM-labeled ZBA248 binding to recombinant human BRD4 bromodomain 1 (44 to 168 residues) expressed in Rosetta2 Escherichia coli DE3 cells after 30 mins by fluorescence polarization assay	ki	0.0007	uM
8-(3,5-difluoro-2-pyridinyl)-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	1289228: Binding affinity to His-tagged BRD4 bromodomain1 (unknown origin) incubated for 1 hr in presence of Europium Cryptate-labeled streptavidin by TR-FRET assay	ic50	0.0007	uM
2-[7-(3,5-dimethyltriazol-4-yl)-9-fluoro-5-[(S)-oxan-4-yl(phenyl)methyl]pyrido[3,2-b]indol-3-yl]propan-2-ol	1807576: Inhibition of BRD4 (unknown origin)	ic50	0.0007	uM
4-[2-(2,4-difluorophenoxy)-5-ethylsulfonylphenyl]-N-ethyl-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridine-2-carboxamide	1548944: Inhibition of human N-terminal His6 tagged BRD4 BD2 (352 to 457) residues expressed in Escherichia coli BL21(DE3) cells after 1 hr by TR-FRET assay	ki	0.0007	uM
4-[2-(3,5-dimethylphenoxy)-5-ethylsulfonylphenyl]-N-ethyl-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridine-2-carboxamide	1548944: Inhibition of human N-terminal His6 tagged BRD4 BD2 (352 to 457) residues expressed in Escherichia coli BL21(DE3) cells after 1 hr by TR-FRET assay	ki	0.0007	uM
N-(10,12-difluoro-23-methyl-22-oxo-8,19-dioxa-6,23-diazatetracyclo[18.4.0.02,7.09,14]tetracosa-1(24),2(7),3,5,9(14),10,12,20-octaen-4-yl)ethanesulfonamide	1481995: Inhibition of human N-terminal His6-tagged BRD4 BD1-BD2 (57 to 550 residues) expressed in EScherichia coli BL21(DE3) after 1 hr by Alexa-647-conjugated probe based TR-FRET assay	ki	0.0008	uM
2-[3-(3,5-dimethyltriazol-4-yl)-8-methoxy-5-[(S)-oxan-4-yl(phenyl)methyl]pyrido[3,2-b]indol-7-yl]propan-2-ol	1870369: Inhibition of N-terminal His6-tagged recombinant human BRD4 (44 to 168 residues) expressed in Escherichia coli BL21 (DE3) incubated for 60 mins by TR-FRET assay	ic50	0.0008	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	1807576: Inhibition of BRD4 (unknown origin)	ic50	0.0008	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	1356122: Binding affinity to human BRD4 bromodomain 2 (K333 to E460 residues) expressed in bacterial expression system by BROMOscan assay	kd	0.0008	uM
7-(3,5-dimethyl-1,2-oxazol-4-yl)-N-(2,5-dimethylpyrazol-3-yl)-6-methoxy-2-methyl-9H-pyrimido[4,5-b]indol-4-amine	1356095: Inhibition of FAM-labeled ZBA248 binding to recombinant human BRD4 bromodomain 1 (44 to 168 residues) expressed in Rosetta2 Escherichia coli DE3 cells after 30 mins by fluorescence polarization assay	ki	0.0008	uM
N-ethyl-4-[5-ethylsulfonyl-2-(2-methylphenoxy)phenyl]-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridine-2-carboxamide	1548944: Inhibition of human N-terminal His6 tagged BRD4 BD2 (352 to 457) residues expressed in Escherichia coli BL21(DE3) cells after 1 hr by TR-FRET assay	ki	0.0008	uM
4-[2-(2,6-dimethylphenoxy)-5-(ethylsulfonylamino)phenyl]-N-ethyl-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridine-2-carboxamide	1548944: Inhibition of human N-terminal His6 tagged BRD4 BD2 (352 to 457) residues expressed in Escherichia coli BL21(DE3) cells after 1 hr by TR-FRET assay	ki	0.0008	uM
4-[2-(4-chloro-2,6-dimethylphenoxy)-5-ethylsulfonylphenyl]-N-ethyl-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridine-2-carboxamide	1548944: Inhibition of human N-terminal His6 tagged BRD4 BD2 (352 to 457) residues expressed in Escherichia coli BL21(DE3) cells after 1 hr by TR-FRET assay	ki	0.0008	uM
12-chloro-4-ethylsulfonyl-23-methyl-8,19-dioxa-23-azatetracyclo[18.4.0.02,7.09,14]tetracosa-1(24),2(7),3,5,9(14),10,12,20-octaen-22-one	1460641: Inhibition of recombinant His-tagged BRD4 (unknown origin) using biotinylated acetyl-histone H4 as substrate by AlphaLisa assay	ic50	0.0009	uM
3-(3,5-dimethyltriazol-4-yl)-7-methylsulfonyl-5-[(S)-oxan-4-yl(phenyl)methyl]pyrido[3,2-b]indole	1870369: Inhibition of N-terminal His6-tagged recombinant human BRD4 (44 to 168 residues) expressed in Escherichia coli BL21 (DE3) incubated for 60 mins by TR-FRET assay	ic50	0.0009	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	1751016: Inhibition of BRD4 (unknown origin)	ic50	0.0009	uM
N-ethyl-4-[5-ethylsulfonyl-2-(2-fluoro-6-methylphenoxy)phenyl]-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridine-2-carboxamide	1548944: Inhibition of human N-terminal His6 tagged BRD4 BD2 (352 to 457) residues expressed in Escherichia coli BL21(DE3) cells after 1 hr by TR-FRET assay	ki	0.0009	uM
4-[2-(2-chloro-6-methylphenoxy)-5-ethylsulfonylphenyl]-N-ethyl-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridine-2-carboxamide	1548944: Inhibition of human N-terminal His6 tagged BRD4 BD2 (352 to 457) residues expressed in Escherichia coli BL21(DE3) cells after 1 hr by TR-FRET assay	ki	0.0009	uM
N-ethyl-4-[5-ethylsulfonyl-2-(1H-indol-7-yl)phenyl]-6-methyl-7-oxo-1H-pyrrolo[2,3-c]pyridine-2-carboxamide	1548944: Inhibition of human N-terminal His6 tagged BRD4 BD2 (352 to 457) residues expressed in Escherichia coli BL21(DE3) cells after 1 hr by TR-FRET assay	ki	0.0009	uM
N-(2-tert-butyl-5-methylpyrazol-3-yl)-7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-2-methyl-9H-pyrimido[4,5-b]indol-4-amine	1356095: Inhibition of FAM-labeled ZBA248 binding to recombinant human BRD4 bromodomain 1 (44 to 168 residues) expressed in Rosetta2 Escherichia coli DE3 cells after 30 mins by fluorescence polarization assay	ki	0.0010	uM
7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-2-methyl-N-(1-methyl-4,5,6,7-tetrahydroindazol-3-yl)-9H-pyrimido[4,5-b]indol-4-amine	1356095: Inhibition of FAM-labeled ZBA248 binding to recombinant human BRD4 bromodomain 1 (44 to 168 residues) expressed in Rosetta2 Escherichia coli DE3 cells after 30 mins by fluorescence polarization assay	ki	0.0010	uM
N-(2-cyclopentyl-5-methylpyrazol-3-yl)-7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-2-methyl-9H-pyrimido[4,5-b]indol-4-amine	1356095: Inhibition of FAM-labeled ZBA248 binding to recombinant human BRD4 bromodomain 1 (44 to 168 residues) expressed in Rosetta2 Escherichia coli DE3 cells after 30 mins by fluorescence polarization assay	ki	0.0010	uM
7-(3,5-dimethyl-1,2-oxazol-4-yl)-6-methoxy-2-methyl-N-(1-methyl-3-propan-2-ylpyrazol-5-yl)-9H-pyrimido[4,5-b]indol-4-amine	1356095: Inhibition of FAM-labeled ZBA248 binding to recombinant human BRD4 bromodomain 1 (44 to 168 residues) expressed in Rosetta2 Escherichia coli DE3 cells after 30 mins by fluorescence polarization assay	ki	0.0010	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
(+)-JQ1 compound	affects response to substance, increases expression, decreases activity, affects cotreatment, increases reaction (+5 more)	38
OTX015	affects binding, decreases reaction, decreases expression, increases expression	3
methylmercuric chloride	increases expression, affects cotreatment	3
bisphenol F	affects cotreatment, increases methylation, increases expression	2
bisphenol A	decreases expression, increases methylation	2
benzyloxycarbonylleucyl-leucyl-leucine aldehyde	decreases reaction, increases degradation, affects localization	2
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	2
Acetaminophen	decreases expression	2
Cisplatin	decreases expression	2
Hydrogen Peroxide	decreases reaction, increases expression, increases reaction, affects binding, affects cotreatment (+4 more)	2
Cadmium Chloride	decreases expression, increases abundance, decreases methylation, increases expression	2
3-((6-(2-methoxyphenyl)pyrimidin-4-yl)amino)phenyl)methane sulfonamide	affects binding, affects cotreatment, decreases reaction, decreases expression	1
GSK-J4	increases expression	1
6,7-dimethoxy-2-(pyrrolidin-1-yl)-N-(5-(pyrrolidin-1-yl)pentyl)quinazolin-4-amine	decreases expression	1
ARV-825	increases degradation, decreases reaction	1
mivebresib	increases expression	1
TAK-243	decreases sumoylation	1
apabetalone	affects cotreatment, decreases expression, decreases phosphorylation	1
ML385	affects reaction, increases activity, affects localization	1
dicrotophos	increases expression	1
triphenyl phosphate	affects expression	1
sanguinarine	affects binding, decreases activity	1
cobaltiprotoporphyrin	affects binding, increases reaction, affects localization, increases expression	1
methylparaben	increases expression	1
tris(1,3-dichloro-2-propyl)phosphate	increases expression	1
sodium arsenite	increases expression	1
perfluorooctanoic acid	decreases expression	1
ochratoxin A	decreases expression	1
aflatoxin B2	increases methylation	1
coumarin	decreases phosphorylation	1

ChEMBL screening assays

4603 unique, capped per target: 4569 binding, 30 functional, 4 admet

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1832850	Binding	Binding affinity to second bromodomain of BRD4 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
CHEMBL4668935	ADMET	Binding affinity to N-terminal His-tagged BRD4 BD1 (unknown origin) by isothermal calorimetric titration 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
CHEMBL5210017	Functional	Affinity Phenotypic Cellular interaction (Alamar Blue assay (proliferation in A431 cancer cell line)) EUB0000169b BRD4	Affinity Phenotypic Cellular Literature for EUbOPEN Chemogenomics Library wave 3

Cellosaurus cell lines

24 cell lines: 23 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_1664	RPMI-2650	Cancer cell line	Male
CVCL_3220	Ty-82	Cancer cell line	Female
CVCL_5132	HCC2429	Cancer cell line	Female
CVCL_B0ZW	Abcam MCF-7 BRD4 KO	Cancer cell line	Female
CVCL_B8C5	Abcam HCT 116 BRD4 KO	Cancer cell line	Male
CVCL_B9EB	Abcam A-549 BRD4 KO	Cancer cell line	Male
CVCL_C8YK	PER-403	Cancer cell line	Female
CVCL_C8YV	A549 PPM1H-BromoTag	Cancer cell line	Male
CVCL_C8YW	PER-624	Cancer cell line	Female
CVCL_C8YX	PER-704	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT05657860	PHASE4	COMPLETED	Guanfacine Extended Release for the Reduction of Aggression and Self-injurious Behavior Associated With Prader-Willi Syndrome
NCT05744479	PHASE4	RECRUITING	Metformin for Antipsychotic-induced Weight Gain in Adults With Intellectual Disability
NCT06107829	PHASE4	WITHDRAWN	Valbenazine Treatment of Tardive Dyskinesia in Adults With Intellectual/Developmental Disabilities
NCT06997198	PHASE4	NOT_YET_RECRUITING	Deutetrabenazine Treatment for Tardive Dyskinesia in Intellectual/Developmental Disabilities
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02270736	PHASE3	COMPLETED	Clinical Study to Investigate the Efficacy and Safety of NT 201 Compared to Placebo in the Treatment of Chronic Troublesome Drooling Associated With Neurological Disorders and/or Intellectual Disability
NCT04381897	PHASE2	NOT_YET_RECRUITING	Use of N-Acetylcysteine in the Treatment of Repetitive and Self-Injurious Behaviors in Cornelia de Lange Syndrome
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT02304302	PHASE2	COMPLETED	Down Syndrome Memantine Follow-up Study
NCT03862950	PHASE2	COMPLETED	A Trial of Metformin in Individuals With Fragile X Syndrome (Met)
NCT04529226	PHASE2	UNKNOWN	Study to Compare Clozapine vs Treatment as Usual in People With Intellectual Disability & Treatment-resistant Psychosis
NCT04821856	PHASE2	COMPLETED	Evaluation of the Effectiveness of Cannabidiol in Treating Severe Behavioural Problems in Children and Adolescents With Intellectual Disability
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	PHASE1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT05273320	PHASE1	COMPLETED	Clinical Trial of Nabilone for Aggression in Adults With Intellectual and Developmental Disabilities
NCT05301361	PHASE1	ENROLLING_BY_INVITATION	Sensitivity of the NIH Toolbox to Stimulant Treatment in Intellectual Disabilities
NCT06016764	PHASE1	COMPLETED	Use of MRI and cTBS for Catatonia in Autism
NCT06586827	PHASE1	COMPLETED	Impact of Competency-Based Training and Technical Assistance Employment Outcomes of Individuals With ID/DD
NCT07531940	PHASE1	NOT_YET_RECRUITING	Escalating Doses of Memantine in Down Syndrome (MEDS-123)
NCT06789783	PHASE2/PHASE3	RECRUITING	Cornelia De Lange Syndrome: Assessing Positive Effects of Lithium Treatment
NCT01793168	Not specified	RECRUITING	Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
NCT03113877	Not specified	TERMINATED	Evaluation of Autonomic Function in Individuals With Cornelia de Lange Syndrome (CdLS)
NCT04463316	Not specified	RECRUITING	GROWing Up With Rare GENEtic Syndromes
NCT05829668	Not specified	RECRUITING	Behavioral Assessment and Treatment of Problem Behavior in Children With Cornelia de Lange Syndrome
NCT01783041	PHASE2/PHASE3	COMPLETED	Effect of Early L-Carnitine Supplementation on Neurodevelopmental Outcomes in Very Preterm Infants
NCT05767385	PHASE2/PHASE3	RECRUITING	Fetal Cerebrovascular Autoregulation in Congenital Heart Disease and Association With Neonatal Neurobehavior
NCT05675098	EARLY_PHASE1	NOT_YET_RECRUITING	Central Nervous System Stimulants and Physical Function in Children With Cerebral Palsy
NCT00783783	Not specified	COMPLETED	CYP2D6 Pharmacogenetics in Risperidone-Treated Children
NCT01778504	Not specified	RECRUITING	Studying Childhood-onset Behavioral, Psychiatric, and Developmental Disorders
NCT01850784	Not specified	UNKNOWN	High Energy Formula Feeding in Infants With Congenital Heart Disease
NCT01922791	Not specified	COMPLETED	Nutrition and Pregnancy Intervention Study
NCT01942525	Not specified	UNKNOWN	Influence of Intrauterine Growth Restriction on Amplitude-integrated EEG in Preterm Infants