HDAC3

Summary

HDAC3 (histone deacetylase 3, HGNC:4854) is a protein-coding gene on chromosome 5q31.3, encoding Histone deacetylase 3 (O15379). Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4), and some other non-histone substrates. It is a common-essential gene (DepMap: required in 95.1% of cancer cell lines).

Histones play a critical role in transcriptional regulation, cell cycle progression, and developmental events. Histone acetylation/deacetylation alters chromosome structure and affects transcription factor access to DNA. The protein encoded by this gene belongs to the histone deacetylase/acuc/apha family. It has histone deacetylase activity and represses transcription when tethered to a promoter. It may participate in the regulation of transcription through its binding with the zinc-finger transcription factor YY1. This protein can also down-regulate p53 function and thus modulate cell growth and apoptosis. This gene is regarded as a potential tumor suppressor gene.

Source: NCBI Gene 8841 — RefSeq curated summary.

At a glance

• Gene–disease (curated): complex neurodevelopmental disorder (Strong, GenCC) — +1 more curated relationship
• GWAS associations: 1
• Clinical variants (ClinVar): 53 total — 1 likely-pathogenic
• Regional missense constraint (gnomAD): 1 of 5 regions constrained (≈9% of expected missense variation)
• GTEx eGene: eQTL in 16 tissues, sQTL in 35 (q < 0.05)
• Drug target: yes — 2 curated mechanism-of-action drugs; 37 molecules with ChEMBL bioactivity (top 1% of genes corpus-wide)
• Approved drugs (ChEMBL mechanism of action): 1 — Vorinostat
• Cancer dependency (DepMap): dependent in 95.1% of screened cell lines (common-essential)
• Constraint (gnomAD): pLI 1.00 (loss-of-function intolerant), LOEUF 0.46 (moderately constrained)
• Transcription factor: yes — 27 downstream targets (CollecTRI)
• MANE Select transcript: NM_003883
• Interaction hub: 3,713 STRING partners (top 1% of genes corpus-wide)

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:4854
Approved symbol	HDAC3
Name	histone deacetylase 3
Location	5q31.3
Locus type	gene with protein product
Status	Approved
Aliases	RPD3, HD3, RPD3-2, KDAC3
Ensembl gene	ENSG00000171720
Ensembl biotype	protein_coding
OMIM	605166
Entrez	8841

Gene structure

Transcript identifiers

Ensembl transcripts: 71 — 36 nonsense_mediated_decay, 22 protein_coding, 11 retained_intron, 2 protein_coding_CDS_not_defined

MANE Select: ENST00000305264

Transcript support level (Ensembl TSL; 1 = fully mRNA-supported): TSL 1: 2, TSL 2: 2, TSL 3: 10, TSL 5: 2

ENST00000305264, ENST00000459727, ENST00000467533, ENST00000469207, ENST00000469550, ENST00000471968, ENST00000475549, ENST00000476739, ENST00000486618, ENST00000490808, ENST00000491581, ENST00000492407, ENST00000492506, ENST00000495485, ENST00000519474, ENST00000523088, ENST00000856306, ENST00000856307, ENST00000856308, ENST00000856309, ENST00000937590, ENST00000937591, ENST00000937592, ENST00000937593, ENST00000937594, ENST00000937595, ENST00000937596, ENST00000940957, ENST00000940958, ENST00000940959, ENST00000940960, ENST00000989160, ENST00000989161, ENST00000989162, ENST00000989163, ENST00000989164, ENST00000989165, ENST00000989166, ENST00000989170, ENST00000989172, ENST00000989173, ENST00000989174, ENST00000989175, ENST00001012852, ENST00001012854, ENST00001012855, ENST00001012856, ENST00001012857, ENST00001012859, ENST00001012860, ENST00001012861, ENST00001070236, ENST00001070237, ENST00001070238, ENST00001070239, ENST00001070240, ENST00001070241, ENST00001070242, ENST00001070243, ENST00001070244, ENST00001070246, ENST00001070247, ENST00001070248, ENST00001107156, ENST00001107157, ENST00001112647, ENST00001112648, ENST00001112649, ENST00001112650, ENST00001130574, ENST00001133863

RefSeq mRNA: 4 — MANE Select: NM_003883 NM_001355039, NM_001355040, NM_001355041, NM_003883

CCDS: CCDS4264

Canonical transcript exons

ENST00000305264 — 15 exons

Exon	Start	End
ENSE00001843922	141636736	141636849
ENSE00003486602	141625208	141625365
ENSE00003494328	141629860	141629916
ENSE00003519531	141620881	141621537
ENSE00003521725	141636548	141636630
ENSE00003526413	141626194	141626283
ENSE00003532204	141634811	141634953
ENSE00003551002	141630044	141630125
ENSE00003572306	141629173	141629306
ENSE00003594264	141628559	141628639
ENSE00003616580	141626013	141626071
ENSE00003628406	141628114	141628187
ENSE00003664475	141629684	141629739
ENSE00003666524	141627893	141627957
ENSE00003691793	141625685	141625764

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 96.90.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 9.1425 / max 53.9948, expressed in 1773 samples.

Highest expression (Bgee): hemisphere of cerebellum, lower esophagus mucosa, cerebellar hemisphere, adrenal gland cortex, cerebellar cortex.

Genetic regulation across tissues (GTEx eQTL / sQTL)

HDAC3 is an eGene in GTEx v10 — its expression is genetically regulated (eQTL) in 16 tissues and its splicing (sQTL) in 35 (q < 0.05). Strongest associations first; slope = normalized effect of the lead variant’s alternative allele.

showing 20 of 51 significant tissue × QTL associations:

Tissue	QTL	q-value	Slope	Lead variant
Thyroid	sqtl	1.9e-30	-0.66	5:141634927:T:C
Esophagus Mucosa	sqtl	1.0e-20	-0.63	5:141634927:T:C
Nerve Tibial	sqtl	9.0e-20	-0.59	5:141634927:T:C
Breast Mammary Tissue	sqtl	5.4e-17	-0.57	5:141634927:T:C
Skin Sun Exposed Lower leg	sqtl	1.5e-14	-0.45	5:141634927:T:C
Artery Aorta	sqtl	6.2e-14	-0.54	5:141634927:T:C
Cells EBV-transformed lymphocytes	sqtl	1.4e-13	-0.63	5:141526863:A:AT
Colon Transverse	sqtl	8.0e-13	-0.58	5:141575387:A:G
Cells Cultured fibroblasts	sqtl	1.2e-12	-0.47	5:141634927:T:C
Esophagus Muscularis	sqtl	1.2e-11	-0.47	5:141538221:T:C
Whole Blood	sqtl	1.8e-11	-0.44	5:141601680:C:A
Testis	sqtl	8.7e-11	-0.67	5:141636721:T:G
Skin Not Sun Exposed Suprapubic	sqtl	1.3e-09	-0.41	5:141634927:T:C
Adipose Visceral Omentum	sqtl	2.1e-09	-0.45	5:141634927:T:C
Heart Atrial Appendage	sqtl	6.5e-09	-0.56	5:141520217:G:C
Cells Cultured fibroblasts	eqtl	6.8e-09	+0.13	5:141601680:C:A
Muscle Skeletal	sqtl	1.5e-08	-0.36	5:141634927:T:C
Adipose Subcutaneous	sqtl	5.8e-08	-0.38	5:141634927:T:C
Esophagus Gastroesophageal Junction	sqtl	1.2e-07	-0.49	5:141610281:A:G
Prostate	sqtl	2.2e-07	-0.58	5:141634927:T:C

FANTOM5 promoters

2 alternative TSS:

Promoter ID	TPM avg	Samples expressed
63857	8.6221	1769
63858	0.5204	196

Top tissues by expression

showing 100 of 299 tissues by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	96.90	gold quality
lower esophagus mucosa	UBERON:0035834	96.88	gold quality
cerebellar hemisphere	UBERON:0002245	96.74	gold quality
right adrenal gland cortex	UBERON:0035827	96.63	gold quality
cerebellar cortex	UBERON:0002129	96.60	gold quality
right adrenal gland	UBERON:0001233	96.40	gold quality
left adrenal gland	UBERON:0001234	96.18	gold quality
left adrenal gland cortex	UBERON:0035825	96.10	gold quality
skin of leg	UBERON:0001511	95.97	gold quality
granulocyte	CL:0000094	95.91	gold quality
skin of abdomen	UBERON:0001416	95.85	gold quality
adenohypophysis	UBERON:0002196	95.85	gold quality
right ovary	UBERON:0002118	95.61	gold quality
right lobe of thyroid gland	UBERON:0001119	95.57	gold quality
left ovary	UBERON:0002119	95.55	gold quality
ganglionic eminence	UBERON:0004023	95.29	gold quality
left lobe of thyroid gland	UBERON:0001120	95.25	gold quality
adrenal gland	UBERON:0002369	95.17	gold quality
adrenal cortex	UBERON:0001235	95.15	gold quality
body of pancreas	UBERON:0001150	95.12	gold quality
ventricular zone	UBERON:0003053	95.08	gold quality
ectocervix	UBERON:0012249	95.02	gold quality
body of uterus	UBERON:0009853	94.92	gold quality
esophagus mucosa	UBERON:0002469	94.89	gold quality
cerebellum	UBERON:0002037	94.86	gold quality
left uterine tube	UBERON:0001303	94.75	gold quality
right lobe of liver	UBERON:0001114	94.71	gold quality
minor salivary gland	UBERON:0001830	94.69	gold quality
pituitary gland	UBERON:0000007	94.66	gold quality
endocervix	UBERON:0000458	94.64	gold quality
zone of skin	UBERON:0000014	94.54	gold quality
esophagus	UBERON:0001043	94.54	gold quality
mucosa of stomach	UBERON:0001199	94.46	gold quality
metanephros cortex	UBERON:0010533	94.43	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	94.42	gold quality
spleen	UBERON:0002106	94.39	gold quality
lower esophagus	UBERON:0013473	94.39	gold quality
lower esophagus muscularis layer	UBERON:0035833	94.38	gold quality
thyroid gland	UBERON:0002046	94.33	gold quality
small intestine Peyer’s patch	UBERON:0003454	94.23	gold quality
muscle layer of sigmoid colon	UBERON:0035805	94.23	gold quality
right frontal lobe	UBERON:0002810	94.11	gold quality
pancreas	UBERON:0001264	94.05	gold quality
body of stomach	UBERON:0001161	94.00	gold quality
right uterine tube	UBERON:0001302	93.99	gold quality
monocyte	CL:0000576	93.96	gold quality
rectum	UBERON:0001052	93.89	gold quality
leukocyte	CL:0000738	93.86	gold quality
right coronary artery	UBERON:0001625	93.80	gold quality
mononuclear cell	CL:0000842	93.79	gold quality
descending thoracic aorta	UBERON:0002345	93.79	gold quality
tibial nerve	UBERON:0001323	93.78	gold quality
transverse colon	UBERON:0001157	93.76	gold quality
stromal cell of endometrium	CL:0002255	93.75	gold quality
islet of Langerhans	UBERON:0000006	93.75	gold quality
thoracic aorta	UBERON:0001515	93.70	gold quality
embryo	UBERON:0000922	93.69	gold quality
ascending aorta	UBERON:0001496	93.67	gold quality
mouth mucosa	UBERON:0003729	93.57	gold quality
apex of heart	UBERON:0002098	93.45	gold quality
gall bladder	UBERON:0002110	93.41	gold quality
mucosa of transverse colon	UBERON:0004991	93.41	gold quality
upper lobe of left lung	UBERON:0008952	93.27	gold quality
smooth muscle tissue	UBERON:0001135	93.25	gold quality
aorta	UBERON:0000947	93.24	gold quality
gastrocnemius	UBERON:0001388	93.21	gold quality
lymph node	UBERON:0000029	93.17	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	93.08	gold quality
left coronary artery	UBERON:0001626	93.08	gold quality
tibial artery	UBERON:0007610	93.08	gold quality
popliteal artery	UBERON:0002250	93.07	gold quality
ovary	UBERON:0000992	93.06	gold quality
muscle of leg	UBERON:0001383	93.01	gold quality
hindlimb stylopod muscle	UBERON:0004252	92.94	gold quality
small intestine	UBERON:0002108	92.92	gold quality
secondary oocyte	CL:0000655	92.91	gold quality
stomach	UBERON:0000945	92.91	gold quality
oocyte	CL:0000023	92.90	gold quality
vagina	UBERON:0000996	92.88	gold quality
right atrium auricular region	UBERON:0006631	92.68	gold quality
cortical plate	UBERON:0005343	92.66	gold quality
colonic epithelium	UBERON:0000397	92.60	gold quality
upper lobe of lung	UBERON:0008948	92.51	gold quality
heart left ventricle	UBERON:0002084	92.47	gold quality
olfactory segment of nasal mucosa	UBERON:0005386	92.44	gold quality
omental fat pad	UBERON:0010414	92.44	gold quality
peritoneum	UBERON:0002358	92.40	gold quality
coronary artery	UBERON:0001621	92.38	gold quality
saliva-secreting gland	UBERON:0001044	92.32	gold quality
Brodmann (1909) area 9	UBERON:0013540	92.27	gold quality
blood	UBERON:0000178	92.15	gold quality
adipose tissue of abdominal region	UBERON:0007808	92.08	gold quality
pancreatic ductal cell	CL:0002079	92.06	gold quality
cardiac ventricle	UBERON:0002082	92.02	gold quality
cardiac atrium	UBERON:0002081	91.87	gold quality
right lung	UBERON:0002167	91.86	gold quality
sigmoid colon	UBERON:0001159	91.80	gold quality
intestine	UBERON:0000160	91.79	gold quality
nucleus accumbens	UBERON:0001882	91.78	gold quality
colon	UBERON:0001155	91.75	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	7.89
E-MTAB-6379	no	523.57

HPA expression

RNA tissue specificity: Low tissue specificity

showing 60 of 80 HPA tissues / cells by nTPM:

Tissue / cell	Axis	nTPM	Protein (IHC)
Frontal cortex	tissue	60.4
Caudate putamen	tissue	57.6
Parathyroid gland	tissue	42.3	low
Tonsil	tissue	40.0	medium
Liver	tissue	37.1	low
Thymus	tissue	35.7
Bone marrow	tissue	35.2	low
Tongue	tissue	31.8
Skin 1	tissue	31.0	medium
Lymph node	tissue	30.6	medium
Skeletal muscle	tissue	30.3	low
Ovary	tissue	30.2	low
Adrenal gland	tissue	28.0	medium
Pancreas	tissue	26.8	medium
Esophagus	tissue	26.4	low
Vagina	tissue	25.5	medium
Fallopian tube	tissue	25.0	medium
Epididymis	tissue	24.9	high
Urinary bladder	tissue	24.5	high
Smooth muscle	tissue	24.4	medium
Superior colliculi	tissue	23.8
Breast	tissue	23.7	medium
Cerebral cortex	tissue	23.7	high
Somatosensory cortex	tissue	23.7
Thalamus	tissue	23.5
Rectum	tissue	23.0	medium
Midbrain	tissue	23.0
Heart muscle	tissue	22.8	medium
Kidney	tissue	22.6	medium
Thyroid gland	tissue	22.5	medium
Hippocampal formation	tissue	22.3
Septum	tissue	22.3
Pons	tissue	21.9
Basal ganglia	tissue	21.8	medium
Colon	tissue	21.7	medium
Cerebellum	tissue	21.7	high
Substantia nigra	tissue	21.6
Salivary gland	tissue	21.4	low
Appendix	tissue	21.4	medium
Entorhinal cortex	tissue	21.3
Occipital cortex	tissue	21.3
Motor cortex	tissue	21.1
Putamen	tissue	21.0
Placenta	tissue	21.0	medium
Spinal cord	tissue	21.0
Cervix	tissue	20.9	medium
Temporal cortex	tissue	20.8
Seminal vesicle	tissue	20.7	medium
Hypothalamus	tissue	20.6
Prefrontal cortex	tissue	20.5
Ventral forebrain	tissue	20.5
Medulla oblongata	tissue	20.4
Lung	tissue	20.2	low
Spleen	tissue	20.2	low
Retrosplenial and cingulate cortex	tissue	20.2
Endometrium 1	tissue	19.9	medium
Olfactory bulb	tissue	19.6
Insular cortex	tissue	19.5
Prostate	tissue	19.3	medium
Periaqueductal gray	tissue	19.3

Brain sub-regions (HPA Brain Atlas): detected in 192; highest nTPM — Blood vessel (25.6), Dorsal hippocampus (22.3), Ventral hippocampus (21.7), Subiculum (21.1), Ventral spinal cord (21.0).

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

27 targets:

Target	Regulation
ALOX5	Activation
APOC3	Unknown
ATP6V0E2	Repression
BGLAP	Unknown
CDH1	Repression
CDKN2A	Repression
CXCR4	Repression
EGFR	Unknown
GAS2	Repression
GATA2	Repression
GCM1	Unknown
GRHL1	Repression
GTF2I	Unknown
IFNA1	Repression
JUN	Repression
LGALS9	Unknown
LSS	Unknown
MBD1	Unknown
MMP2	Repression
MYC	Repression
PCK2	Unknown
PRAM1	Unknown
SMAD7
TLR9	Unknown
TNF	Unknown
ULBP1	Unknown
VEGFA	Unknown

Upstream regulators (CollecTRI, top): HDAC4, MYC, VDR, YY1

miRNA regulators (miRDB)

Targeting HDAC3 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific).

27 miRNAs:

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-4650-5P	99.98	64.69	999
HSA-MIR-6825-5P	99.96	69.81	3431
HSA-MIR-4694-3P	99.79	69.53	2640
HSA-MIR-3934-5P	99.67	64.04	846
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-4644	99.35	69.12	2514
HSA-MIR-6828-5P	99.31	69.21	1433
HSA-MIR-6731-5P	99.28	67.42	2375
HSA-MIR-8085	99.28	67.56	2362
HSA-MIR-6510-5P	99.14	66.59	1081
HSA-MIR-7854-3P	99.08	66.26	1117
HSA-MIR-6506-5P	99.04	65.66	1386
HSA-MIR-330-5P	98.73	67.63	1788
HSA-MIR-589-5P	98.72	66.96	927
HSA-MIR-1261	98.62	68.10	896
HSA-MIR-9500	98.62	66.54	1845
HSA-MIR-619-5P	98.57	64.97	1988
HSA-MIR-326	98.25	66.44	1565
HSA-MIR-6870-3P	98.08	65.10	692
HSA-MIR-6729-3P	96.91	66.79	703
HSA-MIR-3189-3P	96.80	66.34	896
HSA-MIR-4264	96.35	64.76	1480
HSA-MIR-6510-3P	84.92	61.55	36

Functional genomics

gnomAD constraint: pLI 0.998, LOEUF 0.463, missense Z 4.78 — population loss-of-function intolerance (pLI ≥ 0.9 = LoF-intolerant; lower LOEUF = more constrained). gnomAD

Regional missense constraint (gnomAD)

ENST00000305264 splits into 5 regions with different missense tolerance; 1 is missense-constrained (≈9% of the expected missense variation). Missense variants in a constrained region (low observed/expected) are more likely to be pathogenic. gnomAD

Region (GRCh38)	Missense obs / exp	o/e	Constrained
5:141,621,471–141,625,292	44 / 64.3	0.68	no
5:141,625,293–141,634,841	156 / 383.9	0.41	no
5:141,634,842–141,634,925	32 / 37.4	0.86	no
5:141,634,926–141,636,742	16 / 50.1	0.32	yes (p 1.5e-06)
5:141,636,743–141,636,790	22 / 21.3	1.03	no
DepMap (CRISPR cell-line fitness): dependent in 95.1% of screened cell lines, common-essential.

Most-dependent cell lines (DepMap gene-effect, lower = stronger; ≤ −0.5 shown): Hs 852.T (-2.664), NOMO-1 (-2.303), A-375 (-2.243), BHT-101 (-2.167), JVM-3 (-2.103), CAL-120 (-2.065), SNU-1105 (-2.059), CAL-62 (-1.98), NB-4 (-1.968), M059K (-1.964), JH-EsoAd1 (-1.939), SCC-25 (-1.918), BT-549 (-1.906), SNU-213 (-1.892), U343 (-1.886).

Literature-anchored findings (GeneRIF, showing 40)

• Non-permissive cells contain the class I HDAC, HDAC3; super-expression of HDAC3 in normally permissive cells reduces infection and MIEP activity. (PMID:11867539)
• Results show that the N-CoR-HDAC3 complex inhibits JNK activation through the associated GPS2 subunit and thus could potentially provide an alternative mechanism for hormone-mediated antagonism of AP-1 function. (PMID:11931768)
• c-Jun phosporylation mediates dissociation of an inhibitory complex associated with HDAC3. (PMID:12853483)
• N-CoR/histone deacetylase 3 complex is required for repression by thyroid hormone receptor (PMID:12861000)
• the zinc fingers of nuclear receptors provide a general interaction interface for HDACs 3 and 4, recruiting HDACs 3 and 4 to the target DNA causing demonstrable histone deacetylation (PMID:12943985)
• HDAC3 regulates osteoblast differentiation and bone formation; data show that HDAC3 actively regulates the transcriptional activity of the osteoblast master protein, Runx2. (PMID:15292260)
• HDAC3 interacts directly and selectively with MAPK11/p38 beta isoform, represses ATF-2 transcriptional activity, and acts as a regulator of tumor necrosis factor gene expression in lipopolysaccharide-stimulated cells, especially in mononuclear phagocytes. (PMID:15356147)
• THAP7 coimmunoprecipitates with histone deacetylase 3 and the nuclear hormone receptor corepressor and represses transcription (PMID:15561719)
• CMV IE1 interacts specifically with HDAC3 within infected cells, fundamental to transcriptional activation by IE1 (PMID:15572445)
• the N-CoR/HDAC3 complex has a role in regulating the expression of genes involved in circadian rhythm by functioning as corepressor for Rev-erbalpha (PMID:15761026)
• Repression of Dlk1 requires HDAC3 deacetylase activity, which is recruited to the endogenous Dlk1 promoter where it interacts with KLF6. The interaction between HDAC3 and KLF6 is identified as a potential mechanism underlying adipogenesis. (PMID:15917248)
• Elevated HDAC3 expression is associated with squamous cell lung carcinomas (PMID:16022908)
• Data show that LAP2beta interacts at the nuclear envelope with HDAC3, a class-I histone deacetylase, and that TSA (an HDAC inhibitor) abrogates LAP2beta’s transcriptional repressive activity. (PMID:16129885)
• when complexed with Smad6, silences transcriptional activity of glucocorticoid receptor (PMID:16249187)
• the inhibition of p15(INK4b) and p21(WAF1/cip1) may be one of the mechanisms by which HDAC3 participates in cell cycle regulation and oncogenesis (PMID:16298343)
• PML-RARalpha functions by recruiting an HDAC3-MBD1 complex that contributes to the establishment and maintenance of the silenced chromatin state (PMID:16432238)
• This study shows that SMRT/NCoR-HDAC3 complex is a cofactor of CNOT2-mediated repression and suggest that transcriptional regulation by the Ccr4-Not complex involves regulation of chromatin modification. (PMID:16712523)
• Results provide evidence to show that the HDAC3/N-CoR co-repressor complex is involved in the aberrant transcription regulation in PML-RARalpha-expressing cells. (PMID:16730330)
• beta-globin gene promoters in GM979 cells and in erythroid progenitors demonstrate that RB7 and butyrate induce dissociation of HDAC3. (PMID:16849648)
• HDAC3 is a critical, transcription-independent regulator of mitosis. (PMID:16980585)
• HDAC3 expression is elevated in human astrocytic tumours and its expression pattern is deregulated at the cellular level in high-grade gliomas. (PMID:17007107)
• HDAC3 plays a significant role in the regulation of TNF-alpha-mediated VCAM-1 expression (PMID:17008592)
• HDAC-3 cleavage is crucial for efficient apoptosis induction because it allows the activation of some proapoptotic genes during apoptosis progression. (PMID:17101790)
• These results reveal an unexpected role for HDAC3 and suggest a novel pathway through which MEF2 activity is controlled in vivo. (PMID:17158926)
• Histone deacetylase inhibitors transcriptionally inhibit agonist-induced tissue factor expression in endothelial cells and monocytes by a TF-kappaB- and HDAC3-dependent mechanism. (PMID:17675290)
• High expression of HDAC3 is associated with cancer tissues (PMID:17786334)
• data support a central role for HDAC3 in regulating the cell proliferation and differentiation of colon cancer cells and suggest a potential mechanism by which colon cancers may become resistant to luminal butyrate (PMID:17849419)
• KLF4 might function as an activator or repressor of transcription depending on whether it interacts with co-activators such as p300 and CREB-binding protein or co-repressors such as HDAC3. (PMID:17908689)
• the transcription factor YY1 binds to and recruits HDAC3 to the lanosterol synthase promoter. (PMID:17925399)
• Runx2 and HDAC3 repress BSP gene expression and that this repression is suspended upon osteoblastic cell differentiation. (PMID:17956871)
• pro-IL-16 forms a complex with GABPbeta1 and HDAC3 in suppressing the transcription of Skp2. (PMID:18097041)
• we showed that the known effects of HDACs on differentiation and proliferation of cancer cells observed in vitro can also be confirmed in vivo. (PMID:18212746)
• HDAC3 complex is involved in the formation of functional mitotic spindles and proper kinetochore-microtubule attachment (PMID:18326024)
• Strong prognostic impact of HDAC isoforms in colorectal cancer. (PMID:18347167)
• growth factors inhibit sumoylation of SREBPs through their phosphorylation, thus avoiding the recruitment of an HDAC3 corepressor complex and stimulating the lipid uptake and synthesis required for cell growth. (PMID:18403372)
• Accessible chromatin-associated (histone 3 lysine 9) acetylation state serves as a cornerstone for differentially high expression of effector gene eomesodermin and its target genes perforin 1 and granzyme B in memory CD8 T cells. (PMID:18523274)
• C-terminal region of p300 provides corepressor function and facilitates the recruitment of p300 and HDAC3 to the YY1-binding site and represses the c-Myc promoter. (PMID:18542060)
• HDAC3 overexpression alters the epigenetic programming of colon cancer cells to impact intracellular Wnt signaling and their sensitivity to external growth regulation by vitamin D (PMID:18769117)
• Studies show that cancer cells effectively maintain low levels of pyruvate to prevent inhibition of HDAC1/HDAC3 and thereby to evade cell death. (PMID:18789002)
• role of histone deacetylase 3 (HDAC3) in sister chromatid cohesion and the deacetylation of histone H3 Lys 4 (H3K4) at the centromere (PMID:18832068)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
mus_musculus	Hdac3	ENSMUSG00000024454
rattus_norvegicus	Hdac3	ENSRNOG00000019618
caenorhabditis_elegans		WBGENE00001835

Paralogs (10): HDAC9 (ENSG00000048052), HDAC7 (ENSG00000061273), HDAC4 (ENSG00000068024), HDAC6 (ENSG00000094631), HDAC10 (ENSG00000100429), HDAC5 (ENSG00000108840), HDAC1 (ENSG00000116478), HDAC8 (ENSG00000147099), HDAC11 (ENSG00000163517), HDAC2 (ENSG00000196591)

Mouse-model phenotypes

Observed phenotypes of the mouse ortholog (MGI:1343091) from MGI (Alliance of Genome Resources) — knockout/mutant phenotypes, ranked by annotation count. 53 distinct phenotype terms.

Mouse phenotype (MP)	Records
premature death	2
hepatic steatosis	2
embryonic lethality, complete penetrance	2
increased circulating LDL cholesterol level	1
hypoglycemia	1
abnormal heart morphology	1
abnormal cell death	1
decreased cell proliferation	1
enlarged liver	1
pale liver	1
abnormal hepatocyte morphology	1
decreased body size	1
abnormal lipid level	1
increased circulating triglyceride level	1
cardiac hypertrophy	1
abnormal gastrulation	1
failure of embryo implantation	1
female infertility	1
abnormal glucose homeostasis	1
decreased circulating glucagon level	1
decreased circulating insulin level	1
dilated heart left ventricle	1
increased heart weight	1
increased circulating alanine transaminase level	1
increased liver weight	1

+28 more (showing top 25).

Additional cross-species homologs

Sequence homologs in species beyond Ensembl Compara’s model organisms, by Diamond local protein alignment (% sequence identity; best hit per species). Lower-identity rows are more distant homologs. The matched accessions’ gene symbols aren’t in biobtree yet, so each row shows the UniProt accession.

Organism	UniProt	Identity	Method
Staphylococcus aureus subsp. aureus Mu50	P64375	100.0%	Diamond
Staphylococcus aureus subsp. aureus N315	P64376	100.0%	Diamond
Pongo abelii	Q5RAG0	100.0%	Diamond
Staphylococcus aureus subsp. aureus MSSA476	Q6G8J2	100.0%	Diamond
Staphylococcus aureus subsp. aureus MW2	Q8NW34	100.0%	Diamond
Staphylococcus aureus subsp. aureus COL	Q5HF39	99.7%	Diamond
Bos taurus	Q32PJ8	99.6%	Diamond
Staphylococcus aureus subsp. aureus MRSA252	Q6GFX3	98.5%	Diamond
Xenopus tropicalis	Q28DV3	98.4%	Diamond
Xenopus laevis	Q6IRL9	98.4%	Diamond
Gallus gallus	P56519	98.2%	Diamond
Cricetulus griseus	Q80ZH1	97.0%	Diamond
Tetraodon nigroviridis	Q4SFA0	96.7%	Diamond
Danio rerio	Q803C3	96.7%	Diamond
Oryza sativa Japonica Group	Q6YV04	95.9%	Diamond
Arabidopsis thaliana	Q8H0W2	95.5%	Diamond
Strongylocentrotus purpuratus	P56518	86.9%	Diamond
Drosophila melanogaster	Q94517	82.6%	Diamond
Zea mays	P56521	81.5%	Diamond
Staphylococcus xylosus	Q56195	68.8%	Diamond
Dictyostelium discoideum	Q55FN5	67.1%	Diamond
Schizosaccharomyces pombe 972h-	O59702	66.6%	Diamond
Saccharomyces cerevisiae S288C	P32561	66.6%	Diamond
Bacillus subtilis subsp. subtilis str. 168	P39067	49.0%	Diamond
Burkholderia pseudomallei 1710b	Q3JUN4	43.5%	Diamond
Archaeoglobus fulgidus DSM 4304	O30107	40.8%	Diamond

Genomic neighbors (locus context)

Genes flanking this one on the chromosome (NCBI/Entrez gene neighborhood). Positional context only — some neighbors share regulatory elements (bidirectional promoters, antisense/overlapping transcripts), but chromosomal adjacency is not itself a functional relationship (see Interactions for that).

Symbol	Type	Entrez
DIAPH1-AS1	ncRNA	100505658
DIAPH1-AS2	ncRNA	124901091
DIAPH1	protein-coding	1729
RELL2	protein-coding	285613
FCHSD1	protein-coding	89848
PCDHGA12	protein-coding	26025
PCDHGC3	protein-coding	5098
PCDHGC5	protein-coding	56097
PCDHGC4	protein-coding	56098
PCDHGB7	protein-coding	56099
PCDHGB6	protein-coding	56100
PCDHGB5	protein-coding	56101
PCDHGB3	protein-coding	56102
PCDHGB2	protein-coding	56103
PCDHGB1	protein-coding	56104
PCDHGA11	protein-coding	56105
PCDHGA10	protein-coding	56106
PCDHGA9	protein-coding	56107
PCDHGA7	protein-coding	56108
PCDHGA6	protein-coding	56109
PCDHGA5	protein-coding	56110
PCDHGA4	protein-coding	56111
PCDHGA3	protein-coding	56112
PCDHGA2	protein-coding	56113
PCDHGA1	protein-coding	56114
PCDHGB4	protein-coding	8641
PCDHGA8	protein-coding	9708
ARAP3	protein-coding	64411

Protein

Protein identifiers

Histone deacetylase 3 — O15379 (reviewed: O15379)

Alternative names: Protein deacetylase HDAC3, Protein deacylase HDAC3, RPD3-2, SMAP45

All UniProt accessions (3): O15379, E7ESJ6, E7EW19

UniProt curated annotations — full annotation on UniProt →

Function. Histone deacetylase that catalyzes the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4), and some other non-histone substrates. Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Histone deacetylases act via the formation of large multiprotein complexes, such as N-Cor repressor complex, which activate the histone deacetylase activity. Participates in the BCL6 transcriptional repressor activity by deacetylating the H3 ‘Lys-27’ (H3K27) on enhancer elements, antagonizing EP300 acetyltransferase activity and repressing proximal gene expression. Acts as a molecular chaperone for shuttling phosphorylated NR2C1 to PML bodies for sumoylation. Contributes, together with XBP1 isoform 1, to the activation of NFE2L2-mediated HMOX1 transcription factor gene expression in a PI(3)K/mTORC2/Akt-dependent signaling pathway leading to endothelial cell (EC) survival under disturbed flow/oxidative stress. Regulates both the transcriptional activation and repression phases of the circadian clock in a deacetylase activity-independent manner. During the activation phase, promotes the accumulation of ubiquitinated BMAL1 at the E-boxes and during the repression phase, blocks FBXL3-mediated CRY1/2 ubiquitination and promotes the interaction of CRY1 and BMAL1. The NCOR1-HDAC3 complex regulates the circadian expression of the core clock gene BMAL1 and the genes involved in lipid metabolism in the liver. Also functions as a deacetylase for non-histone targets, such as KAT5, MEF2D, MAPK14, RARA and STAT3. Serves as a corepressor of RARA, mediating its deacetylation and repression, leading to inhibition of RARE DNA element binding. In association with RARA, plays a role in the repression of microRNA-10a and thereby in the inflammatory response. In addition to protein deacetylase activity, also acts as a protein-lysine deacylase by recognizing other acyl groups: catalyzes removal of (2E)-butenoyl (crotonyl), lactoyl (lactyl), 2-hydroxyisobutanoyl (2-hydroxyisobutyryl) and isonicotinyl acyl groups from lysine residues, leading to protein decrotonylation, delactylation, de-2-hydroxyisobutyrylation and deisonicotinylation, respectively. Catalyzes decrotonylation of MAPRE1/EB1. Mediates delactylation NBN/NBS1, thereby inhibiting DNA double-strand breaks (DSBs) via homologous recombination (HR).

Subunit / interactions. Interacts with HDAC7 and HDAC9. Interacts with DAXX, KDM4A, HDAC10 and DACH1. Found in a complex with NCOR1 and NCOR2. Component of the N-Cor repressor complex, at least composed of NCOR1, NCOR2, HDAC3, TBL1X, TBL1R, CORO2A and GPS2. Interacts with BCOR, MJD2A/JHDM3A, NRIP1, PRDM6 and SRY. Interacts with BTBD14B. Interacts with GLIS2. Interacts (via the DNA-binding domain) with NR2C1; the interaction recruits phosphorylated NR2C1 to PML bodies for sumoylation. Component of the Notch corepressor complex. Interacts with CBFA2T3 and NKAP. Interacts with APEX1; the interaction is not dependent on the acetylated status of APEX1. Interacts with ZMYND15. Interacts with SMRT/NCOR2 and BCL6 on DNA enhancer elements. Interacts with INSM1. Interacts with XBP1 isoform 1; the interaction occurs in endothelial cell (EC) under disturbed flow. Interacts (via C-terminus) with CCAR2 (via N-terminus). Interacts with and deacetylates MEF2D. Interacts with BEND3. Interacts with NKAPL. Interacts with DHX36; this interaction occurs in a RNA-dependent manner. Interacts weakly with CRY1; this interaction is enhanced in the presence of FBXL3. Interacts with FBXL3 and BMAL1. Interacts with NCOR1. Interacts with RARA. Interacts with SETD5. (Microbial infection) Interacts with human cytomegalovirus (HHV-5) immediate early protein IE1; this interaction decreases histone acetylation and allows transcriptional activation by the virus.

Subcellular location. Nucleus. Chromosome. Cytoplasm. Cytosol.

Tissue specificity. Widely expressed.

Post-translational modifications. Sumoylated in vitro. Deubiquitinated on ‘Lys-63’-linked ubiquitin chains by USP38; leading to a decreased level of histone acetylation.

Activity regulation. Inositol tetraphosphate (1D-myo-inositol 1,4,5,6-tetrakisphosphate) promotes the histone deacetylase activity by acting as an intermolecular glue between HDAC3 and NCOR2, thereby promoting its association with the N-Cor complex, a prerequisite for the histone deacetylase activity.

Induction. Up-regulated by disturbed flow in umbilical vein endothelial cells in vitro.

Similarity. Belongs to the histone deacetylase family. HD type 1 subfamily.

Isoforms (2)

UniProt ID	Names	Canonical?
O15379-1	1, RPD3-2B	yes
O15379-2	2, RPD3-2A

RefSeq proteins (4): NP_001341968, NP_001341969, NP_001341970, NP_003874* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000286	HDACs	Family
IPR003084	HDAC_I/II	Family
IPR023696	Ureohydrolase_dom_sf	Homologous_superfamily
IPR023801	His_deacetylse_dom	Domain
IPR037138	His_deacetylse_dom_sf	Homologous_superfamily

Pfam: PF00850

Enzyme classification (BRENDA)

• EC 3.5.1.98 — histone deacetylase (BRENDA: 33 organisms, 161 substrates, 590 inhibitors, 88 Km, 32 kcat entries)

Substrate kinetics (BRENDA)

32 substrates with measured Km, best-characterized 15. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
FLUOR DE LYS HDAC8 SUBSTRATE	0.14–1.1	9
AC-KHK(ACETYL)K(ACETYL)-7-AMIDO-4-METHYLCOUMARIN	0.273–2.403	6
FLUOR DE LYS HDAC SUBSTRATE	0.013–0.088	6
AC-FEK(ACETYL)-7-AMIDO-4-METHYLCOUMARIN	0.0023–0.0359	5
AC-GGK(ACETYL)-7-AMIDO-4-METHYLCOUMARIN	0.0043–0.0877	5
AC-GS(PO3)K(ACETYL)-7-AMIDO-4-METHYLCOUMARIN	0.0123–0.0666	5
AC-GSK(ACETYL)-7-AMIDO-4-METHYLCOUMARIN	0.004–0.0241	5
AC-IHK(ACETYL)-7-AMIDO-4-METHYLCOUMARIN	0.0007–0.108	5
AC-KYK(ACETYL)-7-AMIDO-4-METHYLCOUMARIN	0.0044–0.107	4
FLUOR DE LYS	—	4
AC-LYK(ACETYL)-7-AMIDO-4-METHYLCOUMARIN	0.0069–0.03	3
AC-VLK(ACETYL)-7-AMIDO-4-METHYLCOUMARIN	0.0119–0.0221	3
RHK(ACETYL)K(ACETYL)-FLUOROPHORE	0.16–1.1	3
AC-DQK(ACETYL)-7-AMIDO-4-METHYLCOUMARIN	0.0024–0.0165	2
BENZYLOXYCARBONYL-L-LYS(ACETYL)-7-AMIDO-4-METHYL	0.078–0.099	2

Catalyzed reactions (Rhea)

• N(6)-acetyl-L-lysyl-[protein] + H2O = L-lysyl-[protein] + acetate (RHEA:58108)
• N(6)-acetyl-L-lysyl-[histone] + H2O = L-lysyl-[histone] + acetate (RHEA:58196)
• N(6)-(2E)-butenoyl-L-lysyl-[protein] + H2O = (2E)-2-butenoate + L-lysyl-[protein] (RHEA:69172)
• N(6)-(2-hydroxyisobutanoyl)-L-lysyl-[protein] + H2O = 2-hydroxy-2-methylpropanoate + L-lysyl-[protein] (RHEA:69176)
• N(6)-[(S)-lactoyl]-L-lysyl-[protein] + H2O = (S)-lactate + L-lysyl-[protein] (RHEA:81387)
• N(6)-isonicotinyl-L-lysyl-[protein] + H2O = isonicotinate + L-lysyl-[protein] (RHEA:83543)

UniProt features (57 total): helix 17, strand 12, binding site 7, turn 6, mutagenesis site 5, region of interest 2, compositionally biased region 2, chain 1, modified residue 1, splice variant 1, sequence variant 1, sequence conflict 1, active site 1

Structure

Experimental structures (PDB)

1 structures by resolution:

PDB	Title	Method	Resolution (Å)
4A69	Structure of HDAC3 bound to corepressor and inositol tetraphosphate	X-RAY DIFFRACTION	2.06

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O15379-F1	90.73	0.85

Human Protein Atlas

Protein class: Enzymes, ENZYME proteins, Hydrolases, Predicted intracellular proteins, FDA approved drug targets, Small molecule drugs, Essential proteins

Protein evidence: Evidence at protein level

Subcellular location (HPA, imaging): nucleoplasm; cytosol; golgi apparatus

Antibody reliability (HPA): IH supported · IF supported

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)

Position	Role
135

Ligand- & substrate-binding residues (7)

Position	Role
172	Zn(2+)
259	Zn(2+)
265	1D-myo-inositol 1,4,5,6-tetrakisphosphate
17	1D-myo-inositol 1,4,5,6-tetrakisphosphate
21	1D-myo-inositol 1,4,5,6-tetrakisphosphate
25	1D-myo-inositol 1,4,5,6-tetrakisphosphate
170	Zn(2+)

Post-translational modifications (1)

Type	Positions
Phosphoserine	424

Mutagenesis-validated functional residues (5)

Position	Phenotype
17–25	abolished interaction with ncor2 and activation of the histone deacetylase activity.
130–132	impaired protein deacetylase activity without affecting the protein decrotonylase activity.
264–265	abolished interaction with ncor2 and activation of the histone deacetylase activity.
265	abolished interaction with ncor2 and activation of the histone deacetylase activity.
298	strongly decreased protein deacetylase activity.

Function

Pathways and Gene Ontology

Reactome pathways

9 curated (TAS) of 75; 16 disease pathways. Curated-first; evidence = TAS (manually curated) vs IEA (electronic inference).

showing 60 of 75 pathways:

ID	Pathway	Evidence
R-HSA-2894862	Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants ⚕	curated
R-HSA-2644606	Constitutive Signaling by NOTCH1 PEST Domain Mutants ⚕	curated
R-HSA-9609690	HCMV Early Events ⚕	curated
R-HSA-9707564	Cytoprotection by HMOX1	curated
R-HSA-3214815	HDACs deacetylate histones	curated
R-HSA-9029569	NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux	curated
R-HSA-350054	Notch-HLH transcription pathway	curated
R-HSA-400206	Regulation of lipid metabolism by PPARalpha	curated
R-HSA-9701898	STAT3 nuclear events downstream of ALK signaling	curated
R-HSA-1643685	Disease ⚕	—
R-HSA-5663202	Diseases of signal transduction by growth factor receptors and second messengers ⚕	—
R-HSA-9675151	Disorders of Developmental Biology ⚕	—
R-HSA-9697154	Disorders of Nervous System Development ⚕	—
R-HSA-9609646	HCMV Infection ⚕	—
R-HSA-5663205	Infectious disease ⚕	—
R-HSA-9022537	Loss of MECP2 binding ability to the NCoR/SMRT complex ⚕	electronic
R-HSA-9005891	Loss of function of MECP2 in Rett syndrome ⚕	—
R-HSA-9005895	Pervasive developmental disorders ⚕	—
R-HSA-2894858	Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer ⚕	—
R-HSA-2644602	Signaling by NOTCH1 PEST Domain Mutants in Cancer ⚕	—
R-HSA-2644603	Signaling by NOTCH1 in Cancer ⚕	—
R-HSA-9824446	Viral Infection Pathways ⚕	—
R-HSA-5619507	Activation of HOX genes during differentiation	—
R-HSA-5617472	Activation of anterior HOX genes in hindbrain development during early embryogenesis	electronic
R-HSA-9843745	Adipogenesis	—
R-HSA-390471	Association of TriC/CCT with target proteins during biosynthesis	electronic
R-HSA-9711123	Cellular response to chemical stress	—
R-HSA-8953897	Cellular responses to stimuli	—
R-HSA-2262752	Cellular responses to stress	—
R-HSA-390466	Chaperonin-mediated protein folding	—
R-HSA-3247509	Chromatin modifying enzymes	—
R-HSA-4839726	Chromatin organization	—
R-HSA-9909396	Circadian clock	—
R-HSA-73887	Death Receptor Signaling	—
R-HSA-1266738	Developmental Biology	—
R-HSA-9976102	Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	electronic
R-HSA-9917777	Epigenetic regulation by WDR5-containing histone modifying complexes	—
R-HSA-9851695	Epigenetic regulation of adipogenesis genes by MLL3 and MLL4 complexes	—
R-HSA-212165	Epigenetic regulation of gene expression	—
R-HSA-9818564	Epigenetic regulation of gene expression by MLL3 and MLL4 complexes	—
R-HSA-9931509	Expression of BMAL (ARNTL), CLOCK, and NPAS2	electronic
R-HSA-74160	Gene expression (Transcription)	—
R-HSA-212436	Generic Transcription Pathway	—
R-HSA-9707616	Heme signaling	electronic
R-HSA-9006925	Intracellular signaling by second messengers	—
R-HSA-9841922	MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis	electronic
R-HSA-1430728	Metabolism	—
R-HSA-556833	Metabolism of lipids	—
R-HSA-392499	Metabolism of proteins	—
R-HSA-1592230	Mitochondrial biogenesis	—
R-HSA-2122947	NOTCH1 Intracellular Domain Regulates Transcription	electronic
R-HSA-9024446	NR1H2 and NR1H3-mediated signaling	—
R-HSA-1852241	Organelle biogenesis and maintenance	—
R-HSA-1257604	PIP3 activates AKT signaling	—
R-HSA-1989781	PPARA activates gene expression	electronic
R-HSA-6807070	PTEN Regulation	—
R-HSA-391251	Protein folding	—
R-HSA-73857	RNA Polymerase II Transcription	—
R-HSA-9933387	RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression	electronic
R-HSA-8941326	RUNX2 regulates bone development	—

MSigDB gene sets: 426 (showing top): GOBP_CIRCADIAN_RHYTHM, REACTOME_TRANSCRIPTIONAL_REGULATION_OF_WHITE_ADIPOCYTE_DIFFERENTIATION, PID_HDAC_CLASSI_PATHWAY, RNGTGGGC_UNKNOWN, GOBP_ESTABLISHMENT_OF_SPINDLE_ORIENTATION, REACTOME_SIGNALING_BY_NOTCH, AP1_01, GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOBP_EPITHELIUM_DEVELOPMENT, GOBP_REGULATION_OF_EPITHELIAL_CELL_APOPTOTIC_PROCESS, GOBP_MUSCLE_TISSUE_DEVELOPMENT, GOBP_ESTABLISHMENT_OR_MAINTENANCE_OF_CELL_POLARITY, GOBP_NEGATIVE_REGULATION_OF_INTERLEUKIN_1_PRODUCTION, GOBP_REGULATION_OF_PHOSPHORYLATION, GOBP_NEGATIVE_REGULATION_OF_STRIATED_MUSCLE_CELL_DIFFERENTIATION

GO Biological Process (41): negative regulation of transcription by RNA polymerase II (GO:0000122), establishment of mitotic spindle orientation (GO:0000132), in utero embryonic development (GO:0001701), positive regulation of protein phosphorylation (GO:0001934), chromatin organization (GO:0006325), DNA-templated transcription (GO:0006351), protein deacetylation (GO:0006476), response to xenobiotic stimulus (GO:0009410), positive regulation of protein ubiquitination (GO:0031398), regulation of protein stability (GO:0031647), response to nutrient levels (GO:0031667), positive regulation of TOR signaling (GO:0032008), negative regulation of interleukin-1 production (GO:0032692), negative regulation of tumor necrosis factor production (GO:0032720), circadian regulation of gene expression (GO:0032922), epigenetic regulation of gene expression (GO:0040029), positive regulation of protein import into nucleus (GO:0042307), regulation of circadian rhythm (GO:0042752), negative regulation of apoptotic process (GO:0043066), positive regulation of neuron apoptotic process (GO:0043525), negative regulation of DNA-templated transcription (GO:0045892), positive regulation of transcription by RNA polymerase II (GO:0045944), negative regulation of JNK cascade (GO:0046329), negative regulation of protein export from nucleus (GO:0046826), spindle assembly (GO:0051225), negative regulation of transcription initiation by RNA polymerase II (GO:0060633), random inactivation of X chromosome (GO:0060816), establishment of skin barrier (GO:0061436), cellular response to mechanical stimulus (GO:0071260), cellular response to parathyroid hormone stimulus (GO:0071374), cellular response to fluid shear stress (GO:0071498), response to dexamethasone (GO:0071548), positive regulation of cold-induced thermogenesis (GO:0120162), DNA repair-dependent chromatin remodeling (GO:0140861), positive regulation of ferroptosis (GO:0160020), cornified envelope assembly (GO:1903575), positive regulation of type B pancreatic cell apoptotic process (GO:2000676), chromatin remodeling (GO:0006338), epidermis development (GO:0008544), gene expression (GO:0010467), rhythmic process (GO:0048511)

GO Molecular Function (22): transcription corepressor binding (GO:0001222), chromatin binding (GO:0003682), transcription corepressor activity (GO:0003714), histone deacetylase activity (GO:0004407), enzyme binding (GO:0019899), cyclin binding (GO:0030332), chromatin DNA binding (GO:0031490), protein lysine deacetylase activity (GO:0033558), histone deacetylase binding (GO:0042826), GTPase binding (GO:0051020), NF-kappaB binding (GO:0051059), histone isonicotinyllysine deisonicotinylase activity (GO:0140229), DNA-binding transcription factor binding (GO:0140297), histone deacetylase activity, hydrolytic mechanism (GO:0141221), protein decrotonylase activity (GO:0160008), histone decrotonylase activity (GO:0160009), protein de-2-hydroxyisobutyrylase activity (GO:0160010), protein lysine delactylase activity (GO:0160216), ubiquitin-specific protease binding (GO:1990381), DNA binding (GO:0003677), protein binding (GO:0005515), hydrolase activity (GO:0016787)

GO Cellular Component (9): histone deacetylase complex (GO:0000118), chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), cytosol (GO:0005829), transcription repressor complex (GO:0017053), mitotic spindle (GO:0072686), chromosome (GO:0005694)

Reactome top-level categories

20 top-level categories:

Category	Pathways
p75 NTR receptor-mediated signalling	1
Regulation of lipid metabolism by PPARalpha	1
Signaling by NOTCH1	1
Mitochondrial biogenesis	1
Signaling by NOTCH1 PEST Domain Mutants in Cancer	1
Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer	1
Chromatin modifying enzymes	1
Generic Transcription Pathway	1
Adipogenesis	1
Chaperonin-mediated protein folding	1
Metabolism of lipids	1
Activation of HOX genes during differentiation	1
RUNX2 regulates bone development	1
PTEN Regulation	1
Loss of function of MECP2 in Rett syndrome	1
Transcriptional Regulation by MECP2	1
NR1H2 and NR1H3-mediated signaling	1
HCMV Infection	1
Signaling by ALK	1
Cellular response to chemical stress	1

GO top-level categories

showing 60 of 76 GO namespaces:

Category	Terms
cellular anatomical structure	4
histone modifying activity	3
hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides	3
negative regulation of DNA-templated transcription	2
circadian rhythm	2
regulation of gene expression	2
protein binding	2
catalytic activity, acting on a protein	2
enzyme binding	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
mitotic cell cycle	1
establishment of mitotic spindle localization	1
establishment of spindle orientation	1
chordate embryonic development	1
regulation of protein phosphorylation	1
protein phosphorylation	1
positive regulation of protein modification process	1
positive regulation of phosphorylation	1
cellular component organization	1
gene expression	1
RNA biosynthetic process	1
protein deacylation	1
response to chemical	1
protein ubiquitination	1
regulation of protein ubiquitination	1
positive regulation of protein modification by small protein conjugation or removal	1
regulation of biological quality	1
response to stimulus	1
TOR signaling	1
regulation of TOR signaling	1
positive regulation of intracellular signal transduction	1
negative regulation of cytokine production	1
interleukin-1 production	1
regulation of interleukin-1 production	1
tumor necrosis factor production	1
regulation of tumor necrosis factor production	1
negative regulation of tumor necrosis factor superfamily cytokine production	1
chromatin remodeling	1
protein import into nucleus	1
regulation of protein import into nucleus	1
positive regulation of nucleocytoplasmic transport	1
positive regulation of intracellular protein transport	1
positive regulation of protein localization to nucleus	1
regulation of biological process	1
apoptotic process	1
regulation of apoptotic process	1
negative regulation of programmed cell death	1
positive regulation of apoptotic process	1
regulation of neuron apoptotic process	1
neuron apoptotic process	1
transcription coregulator binding	1
binding	1
transcription coregulator activity	1
protein lysine deacetylase activity	1
DNA binding	1
chromatin binding	1
deacetylase activity	1
RNA polymerase II-specific DNA-binding transcription factor binding	1
transcription factor binding	1

Experimentally-supported GO annotations

GO terms backed by direct experimental evidence (ECO experimental codes) — 35 of 72 annotations. The rest are phylogenetic / computational / electronic (IEA).

35 experimentally-supported GO terms:

GO term	NS	Evidence
DNA repair-dependent chromatin remodeling	BP	direct assay
cellular response to fluid shear stress	BP	direct assay
establishment of mitotic spindle orientation	BP	direct assay
negative regulation of DNA-templated transcription	BP	mutant phenotype
negative regulation of JNK cascade	BP	mutant phenotype
negative regulation of transcription by RNA polymerase II	BP	direct assay
positive regulation of TOR signaling	BP	mutant phenotype
positive regulation of ferroptosis	BP	mutant phenotype
positive regulation of protein import into nucleus	BP	direct assay
positive regulation of protein phosphorylation	BP	direct assay
positive regulation of transcription by RNA polymerase II	BP	direct assay
protein deacetylation	BP	direct assay
regulation of protein stability	BP	direct assay
spindle assembly	BP	mutant phenotype
cytoplasm	CC	direct assay
cytosol	CC	direct assay
histone deacetylase complex	CC	direct assay
mitotic spindle	CC	direct assay
nucleoplasm	CC	direct assay
nucleus	CC	direct assay
transcription repressor complex	CC	direct assay
NF-kappaB binding	MF	physical interaction
chromatin binding	MF	direct assay
cyclin binding	MF	physical interaction
enzyme binding	MF	physical interaction
histone deacetylase activity	MF	direct assay
histone deacetylase binding	MF	physical interaction
histone decrotonylase activity	MF	direct assay
histone isonicotinyllysine deisonicotinylase activity	MF	direct assay
protein de-2-hydroxyisobutyrylase activity	MF	direct assay
protein decrotonylase activity	MF	direct assay
protein lysine deacetylase activity	MF	direct assay
protein lysine delactylase activity	MF	direct assay
transcription corepressor activity	MF	direct assay
transcription corepressor binding	MF	physical interaction

Protein interactions and networks

STRING

showing 15 of 3,713 interactions by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HDAC3	NCOR1	O75376	924
HDAC3	H3-7	Q5TEC6	831
HDAC3	H3-5	Q6NXT2	831
HDAC3	H3-3A	P06351	830
HDAC3	H3C1	P02295	830
HDAC3	H3-4	Q16695	830
HDAC3	H3C14	Q71DI3	830
HDAC3	NCOR2	Q9Y618	812
HDAC3	KAT2A	Q92830	798
HDAC3	TBL1Y	Q9BQ87	797
HDAC3	KAT5	Q92993	785
HDAC3	EP300	Q09472	783
HDAC3	MATN3	O15232	782
HDAC3	SIRT1	Q96EB6	767
HDAC3	SAP30	O75446	765

IntAct

Human interaction partners of HDAC3 in IntAct, one row per partner (best MIscore; records = supporting IntAct interaction records).

showing 30 of 76 partners by confidence:

Partner	Interaction type	MIscore	Records
NCOR2	direct interaction	0.950	7
GPS2	physical association	0.900	4
NCOR1	physical association	0.800	1
TBL1X	association	0.760	1
AKAP8	association	0.650	10
KDM1A	association	0.650	4
L3MBTL2	physical association	0.640	6
TBL1XR1	association	0.640	1
AKAP8L	physical association	0.610	2
MAGEA2	direct interaction	0.590	3
MBD1	physical association	0.580	3
PGK1	physical association	0.540	5
CCND1	physical association	0.540	3
MECP2	association	0.530	3
HDAC4	association	0.530	2
GATA3	physical association	0.520	7
ICP0	physical association	0.520	3
HDAC1	physical association	0.520	2
PPP4C	physical association	0.520	2
NRIP1	physical association	0.510	2
RREB1	colocalization	0.510	2
SUZ12	physical association	0.500	5
NR0B2	physical association	0.500	2
APPL1	physical association	0.500	1
TP53	association	0.480	2
ZMYM2	association	0.480	1
MYC	association	0.460	4
SKI	association	0.460	1
SNAI1	deacetylation reaction	0.440	1
ZNF148	colocalization	0.430	3

BioGRID (666 interactions; top human partners by supporting records in a sample of 600 records): NCOR1 (Affinity Capture-Western; 27 records), NCOR2 (Affinity Capture-Western; 25 records), NR2C1 (Reconstituted Complex; 12 records), GPS2 (Affinity Capture-MS; 9 records), HDAC4 (Affinity Capture-MS; 9 records), YY1 (Reconstituted Complex; 9 records), ATXN3 (Affinity Capture-Western; 8 records), PPARG (Affinity Capture-Western; 8 records), TBL1X (Reconstituted Complex; 8 records), AKT1 (Affinity Capture-Western; 6 records), ELL (Affinity Capture-Western; 6 records), GTF2I (Affinity Capture-Western; 6 records), HDAC5 (Affinity Capture-Western; 6 records), TBL1XR1 (Affinity Capture-Western; 6 records), CCND1 (Affinity Capture-Western; 5 records)

SIGNOR signaling

showing 41 of 52 signaling interactions:

A	Effect	B	Mechanism
RB1	up-regulates	HDAC3
BCL3	up-regulates	HDAC3	binding
CCND1	up-regulates	HDAC3	binding
CUDC-907	down-regulates	HDAC3	“chemical inhibition”
4-(4-chloro-2-methylphenoxy)-N-hydroxybutanamide	down-regulates	HDAC3	“chemical inhibition”
entinostat	down-regulates	HDAC3	“chemical inhibition”
N-(2-aminophenyl)-4-[[[4-(3-pyridinyl)-2-pyrimidinyl]amino]methyl]benzamide	down-regulates	HDAC3	“chemical inhibition”
HDAC3	up-regulates	E2F1	binding
HDAC3	up-regulates	HDAC1	binding
HDAC3	up-regulates	SMAD7	binding
3-[(dimethylamino)methyl]-N-[2-[4-[(hydroxyamino)-oxomethyl]phenoxy]ethyl]-2-benzofurancarboxamide	down-regulates	HDAC3	“chemical inhibition”
HDAC3	up-regulates	SMAD7/HDAC1/E2F-1	binding
PPP4C	“down-regulates activity”	HDAC3	dephosphorylation
CSNK2A1	“up-regulates activity”	HDAC3	phosphorylation
BCOR	“up-regulates activity”	HDAC3	binding
JWOGUUIOCYMBPV-GMFLJSBRSA-N	“down-regulates activity”	HDAC3	“chemical inhibition”
(S)-N-Hydroxy-4-(3-methyl-2-phenylbutanamido)benzamide	“down-regulates activity”	HDAC3	“chemical inhibition”
HDAC3	“up-regulates quantity by stabilization”	FASN	deacetylation
HDAC3	“down-regulates quantity by repression”	CDH1	“transcriptional regulation”
GATA1	“up-regulates activity”	HDAC3	relocalization
GSK3B	“up-regulates activity”	HDAC3	phosphorylation
PINK1	“up-regulates activity”	HDAC3	phosphorylation
TBK1	“up-regulates activity”	HDAC3	phosphorylation
HDAC3	“down-regulates quantity by repression”	ATP6V0E2	“transcriptional regulation”
HIPK2	“down-regulates activity”	HDAC3	phosphorylation
belinostat	“down-regulates activity”	HDAC3	“chemical inhibition”
panobinostat	“down-regulates activity”	HDAC3	“chemical inhibition”
entinostat	“down-regulates activity”	HDAC3	“chemical inhibition”
“N-[4-[(hydroxyamino)-oxomethyl]phenyl]carbamic acid [6-(diethylaminomethyl)-2-naphthalenyl]methyl ester”	“down-regulates activity”	HDAC3	“chemical inhibition”
vorinostat	“down-regulates activity”	HDAC3	“chemical inhibition”
N-hydroxy-3-[4-[[2-hydroxyethyl-[2-(1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide	“down-regulates activity”	HDAC3	“chemical inhibition”
N-(2-aminophenyl)-4-[[[4-(3-pyridinyl)-2-pyrimidinyl]amino]methyl]benzamide	“down-regulates activity”	HDAC3	“chemical inhibition”
“trichostatin A”	“down-regulates activity”	HDAC3	“chemical inhibition”
romidepsin	“down-regulates activity”	HDAC3	“chemical inhibition”
6-(1,3-dioxo-2-benzo[de]isoquinolinyl)-N-hydroxyhexanamide	“down-regulates activity”	HDAC3	“chemical inhibition”
tacedinaline	“down-regulates activity”	HDAC3	“chemical inhibition”
CUDC-101	“down-regulates activity”	HDAC3	“chemical inhibition”
CCAR2	“down-regulates activity”	HDAC3	binding
HDAC3	“down-regulates activity”	YY1	deacetylation
ALDH2	“up-regulates activity”	HDAC3	binding
SRC	“up-regulates activity”	HDAC3	phosphorylation

Protein complexes (CORUM) (22)

Experimentally-characterized complexes this protein is a subunit of (★ = the complex contains a known drug target).

22 complexes by size:

Complex	Subunits	Members
★ Emerin complex 32	22	HDAC1, RBL2, SMARCC1, SMARCC2, TBL1Y, BANF2, DPY30, HDAC3, H3C1, LMNB1, MED4, RBL1, SAP18, TRIM28, ACTB, CHD4, EMD, NMI, RCOR1, SMARCB1, SPTAN1, TBL1XR1
★ NCOR1 complex	10	HDAC3, NCOR1, SF3A1, SMARCA4, SMARCB1, SMARCC2, TRIM28, SF3B3, SMARCC1, SRCAP
★ KAISO-NCOR complex	10	GPS2, KIF11, NCOR1, TBL1XR1, ZBTB33, CORO2A, HDAC3, KDM4A, TBL1X, TRIM33
★ Emerin regulatory complex	9	BANF1, EMD, H3C1, LMO7, ACTB, H1-1, HDAC1, HDAC3, RBL1
★ NCOR2 complex	7	NCOR2, SAP30, SIN3A, HDAC1, HDAC2, HDAC3, NCOR1
★ NCOR complex	6	CORO2A, GPS2, HDAC3, NCOR1, TBL1X, TBL1XR1
★ SMRT complex	5	GPS2, HDAC3, NCOR2, TBL1X, TBL1XR1
★ NCOR-HDAC3 complex	5	NCOR1, TBL1X, TBL1XR1, GPS2, HDAC3
★ HDAC3-H1.3-SMRT-N-Cor complex	4	HDAC3, NCOR1, NCOR2, H1-3
★ AJUBA-GFI1-HDAC3 complex	3	HDAC3, AJUBA, GFI1
★ AKT1-APPL1-HDAC3 complex	3	AKT1, APPL1, HDAC3
★ SMRT core complex	3	HDAC3, NCOR2, TBL1X
★ HDAC3-PPARG-RB1 complex	3	RB1, HDAC3, PPARG
★ ANKRD11-HDAC3 complex	2	ANKRD11, HDAC3
★ DTNBP1(1A)-HDAC3 complex	2	HDAC3, DTNBP1
★ DTNBP1(1B)-HDAC3 complex	2	DTNBP1, HDAC3
★ HDAC3-RARA complex	2	HDAC3, RARA
★ CCAR2-HDAC3 complex	2	HDAC3, CCAR2
★ HDAC3-HDAC9 complex	2	HDAC3, HDAC9
★ HDAC3-HDAC10 complex	2	HDAC10, HDAC3
★ HDAC3-STAT3 complex	2	HDAC3, STAT3
★ HDAC3-CCNA2 complex	2	CCNA2, HDAC3

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 76 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
Notch-HLH transcription pathway	11	72.4×	3e-16
NOTCH1 Intracellular Domain Regulates Transcription	13	49.9×	1e-16
Regulation of MECP2 expression and activity	7	41.6×	2e-08
Constitutive Signaling by NOTCH1 PEST Domain Mutants	13	41.3×	4e-16
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants	13	41.3×	4e-16
Signaling by NOTCH1 PEST Domain Mutants in Cancer	6	39.5×	3e-07
Signaling by NOTCH1 in Cancer	6	39.5×	3e-07
Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer	6	39.5×	3e-07

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of miRNA transcription	7	27.5×	2e-06
negative regulation of gene expression, epigenetic	5	27.1×	1e-04
epigenetic regulation of gene expression	5	25.9×	1e-04
B cell differentiation	6	17.8×	1e-04
circadian regulation of gene expression	5	15.8×	1e-03
negative regulation of transforming growth factor beta receptor signaling pathway	6	14.1×	4e-04
transforming growth factor beta receptor signaling pathway	5	10.7×	4e-03
positive regulation of canonical Wnt signaling pathway	5	10.4×	4e-03

Disease & clinical

Genetic variants

Variant evidence for HDAC3: 53 ClinVar records (1 pathogenic / likely pathogenic); 1 GWAS association. Per-variant detail is on Sugi Variant.

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	25
Likely benign	5
Benign	2

Top pathogenic / likely-pathogenic (1)

Showing all 1 pathogenic / likely-pathogenic ClinVar records, ranked by ClinVar review status (expert panel → multiple submitters → single submitter), then by number of submitting labs.

Variant ID	HGVS	Classification	Review	Submitters
520683	NM_003883.4(HDAC3):c.902G>A (p.Arg301Gln)	Likely pathogenic	criteria provided, single submitter	1

Per-variant reference — Sugi Variant

Explore HDAC3’s pathogenic and likely-pathogenic variants individually — each with its ClinVar classification and conditions, applied ACMG criteria (ClinGen expert panel, where curated), the calibrated in-silico predictors (AlphaMissense, REVEL, SaProt, conservation), gnomAD frequency, and the predictor-disagreement QC signal — on Sugi Variant.

SpliceAI

Top 10 splice-impact sites by Δscore (adjacent positions with the same effect merged into one range; 17 predictions of 1,077):

Position(s)	Effect	Δscore	Sites
5:141625194	donor_gain	1.0000
5:141625206–141625207	donor_loss	1.0000	5
5:141625235	donor_gain	1.0000
5:141625370	acceptor_gain	1.0000
5:141625666	donor_gain	1.0000
5:141625766	acceptor_gain	1.0000
5:141628557	donor_loss	1.0000
5:141629171	donor_loss	1.0000
5:141629195	donor_gain	1.0000
5:141629740–141629741	acceptor_loss	1.0000	4

AlphaMissense

1,899 missense substitutions predicted likely pathogenic (of 2,864 scored), across 380 residues. Top 20 hotspot residues, ranked by the number of likely-pathogenic substitutions (of those reachable by a single-nucleotide change), then by mean score:

Residue	Likely-pathogenic substitutions	Mean am_pathogenicity	Max am_pathogenicity
M24	9	0.978	0.999
H135	8	1.000	1.000
D170	8	1.000	1.000
D259	8	1.000	1.000
D264	8	1.000	1.000
D93	8	0.999	1.000
H134	8	0.999	1.000
D149	8	0.999	1.000
D168	8	0.999	1.000
H172	8	0.999	1.000
H173	8	0.999	1.000
D175	8	0.999	1.000
H193	8	0.999	1.000
H62	8	0.998	1.000
F144	8	0.998	1.000
H22	8	0.997	1.000
F97	8	0.997	1.000
H276	8	0.997	0.999
N350	8	0.997	1.000
F181	8	0.996	1.000

HPA cancer prognostics

RNA cancer specificity: Low cancer specificity

Human Protein Atlas survival analysis — favorable = higher expression predicts better survival.

3 prognostic cancer types:

Cancer	Prognostic	p-value
Kidney Renal Clear Cell Carcinoma (TCGA)	favorable	7.82e-06
Liver Hepatocellular Carcinoma (TCGA)	unfavorable	0.00037
Colon Adenocarcinoma (TCGA)	favorable	0.000704

Disease associations

OMIM: gene MIM:605166 | disease phenotypes:

GenCC curated gene-disease

2 curated gene-disease records:

Disease	Classification	Inheritance	Records
complex neurodevelopmental disorder	Strong	Autosomal dominant
neurodevelopmental disorder	Strong	Autosomal dominant	2

Genomics England panels (PanelApp)

Clinical diagnostic gene panels including this gene (6 panels, 6 green/diagnostic-grade). Confidence: green = diagnostic, amber = moderate.

6 panels:

Panel	Rating
DDG2P	green
Fetal anomalies	green
Hypotonic infant	green
Intellectual disability	green
Leukodystrophy, childhood onset	green
Paediatric disorders	green

Mondo (2): complex neurodevelopmental disorder (MONDO:0100038), neurodevelopmental disorder (MONDO:0700092)

GWAS associations

1 associations:

Study	Trait	p-value
GCST010002_114	Refractive error	2e-14

MeSH disease descriptors

1 disease descriptors:

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (14): CHEMBL1829 (SINGLE PROTEIN), CHEMBL2093865 (PROTEIN FAMILY), CHEMBL2111363 (PROTEIN COMPLEX), CHEMBL3038483 (PROTEIN FAMILY), CHEMBL3038484 (PROTEIN COMPLEX), CHEMBL3430896 (PROTEIN FAMILY), CHEMBL3430897 (PROTEIN FAMILY), CHEMBL4296072 (PROTEIN FAMILY), CHEMBL4523679 (PROTEIN-PROTEIN INTERACTION), CHEMBL4523988 (PROTEIN FAMILY)

Drugs by curated mechanism of action (ChEMBL)

Drugs whose curated ChEMBL mechanism of action targets the HDAC3 protein itself — single-protein targets only (drugs acting on a protein family or complex that merely includes it are excluded). Includes antibodies and oligonucleotides that bioactivity screening does not capture.

2 curated-mechanism drugs:

Drug	Modality	Max phase
VORINOSTAT	Small molecule	4
MOCETINOSTAT	Small molecule	2

Molecules with ChEMBL bioactivity

Phase ≥1, by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 873,186 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

37 molecules by phase:

Molecule	Name	Phase	Patents
CHEMBL98	VORINOSTAT	4	51,304
CHEMBL408513	BELINOSTAT	4	8,184
CHEMBL487253	BENDAMUSTINE	4	31,460
CHEMBL325041	BORTEZOMIB	4	13,415
CHEMBL118	CELECOXIB	4	113,751
CHEMBL1213492	GIVINOSTAT	4	2,960
CHEMBL483254	PANOBINOSTAT	4	12,172
CHEMBL1469	PHENYLBUTANOIC ACID	4	37,412
CHEMBL343448	ROMIDEPSIN	4	13,626
CHEMBL1746	SODIUM PHENYLBUTYRATE	4	5,678
CHEMBL2103863	ABEXINOSTAT	3	2,290
CHEMBL145	CAFFEIC ACID	3	36,727
CHEMBL140	CURCUMIN	3	95,185
CHEMBL27759	ENTINOSTAT	3	6,811
CHEMBL1851943	PRACINOSTAT	3	2,099
CHEMBL235191	TACEDINALINE	3	2,995
CHEMBL3621988	TUCIDINOSTAT	3	2,280
CHEMBL272980	MOCETINOSTAT	2	4,030
CHEMBL191482	AR-42	2	2,146
CHEMBL14227	BUTYRIC ACID	2	428,661
CHEMBL284616	CHLOROGENIC ACID	2
CHEMBL3693786	CITARINOSTAT	2
CHEMBL356066	DACINOSTAT	2
CHEMBL4283683	DOMATINOSTAT	2
CHEMBL3622533	FIMEPINOSTAT	2
CHEMBL1801250	NANATINOSTAT	2
CHEMBL2105763	QUISINOSTAT	2
CHEMBL2364628	RICOLINOSTAT	2
CHEMBL62381	SODIUM BUTYRATE	2
CHEMBL3989941	TINOSTAMUSTINE	2
CHEMBL3287255	BISTHIANOSTAT	1
CHEMBL5314582	BOCODEPSIN BESYLATE	1
CHEMBL598797	CUDC-101	1
CHEMBL96	GAMMA-AMINOBUTYRIC ACID	1
CHEMBL353581	PYROXAMIDE	1
CHEMBL609583	R-306465	1
CHEMBL99	TRICHOSTATIN	1

PharmGKB: 1 entry (CPIC guideline: no)

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — Histone deacetylases (HDACs)

Most potent curated ligand interactions (35 total), top 25:

Ligand	Action	Affinity	Parameter
romidepsin	Inhibition	9.82	pKi
trichostatin A	Inhibition	9.3	pKi
martinostat	Inhibition	9.22	pIC50
fimepinostat	Inhibition	8.74	pIC50
BML-281	Inhibition	8.7	pIC50
panobinostat	Inhibition	8.4	pEC50
scriptaid	Inhibition	8.39	pKi
dacinostat	Inhibition	8.38	pKi
quisinostat	Inhibition	8.31	pIC50
vorinostat	Inhibition	8.3	pKi
RGFP109	Inhibition	8.3	pKi
CHR-3996	Inhibition	8.15	pIC50
abexinostat	Inhibition	8.09	pIC50
CUDC-101	Inhibition	8.04	pIC50
givinostat	Inhibition	7.68	pEC50
apicidin	Inhibition	7.52	pEC50
belinostat	Inhibition	7.52	pEC50
pracinostat	Inhibition	7.37	pIC50
citarinostat	Inhibition	7.34	pIC50
inhibitor M9 [PMID: 38236416]	Inhibition	7.31	pIC50
resminostat	Inhibition	7.3	pIC50
ricolinostat	Inhibition	7.29	pIC50
compound 30 [PMID: 37057760]	Inhibition	7.13	pIC50
RGFP966	Inhibition	7.1	pIC50
domatinostat	Inhibition	6.89	pIC50

Binding affinities (BindingDB)

4733 measured of 5791 human assays (5851 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
GNF-Pf-1011	IC50	0.001 nM
CHEMBL6148436	IC50	0.031 nM
CHEMBL6143656	IC50	0.032 nM
(S)-N-((S)-1-(4-chloro-2-(4-fluorophenyl)-1H-imidazol-5-yl)-7-(oxazol-2-yl)-7-oxoheptyl)-6-ethyl-6-azaspiro[2.5]octane-1-carboxamide	IC50	0.049 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
CHEMBL4861467	IC50	0.05 nM
CHEMBL4237803	KI	0.075 nM
CHEMBL6150788	IC50	0.076 nM
CHEMBL6146244	IC50	0.076 nM
N-[(1S)-1-[5-(2-fluorophenyl)-1H-imidazol-2-yl]-7-(1,2-oxazol-3-yl)-7-oxoheptyl]-1-methylazetidine-3-carboxamide	IC50	0.08 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(S)-N-((S)-1-(4-chloro-2-(2-fluorophenyl)-1H-imidazol-5-yl)-7-(isoxazol-3-yl)-7-oxoheptyl)-6-methyl-6-azaspiro[2.5]octane-1-carboxamide	IC50	0.083 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
CHEMBL4649205	IC50	0.085 nM
JNJ-26481585	IC50	0.1 nM
(2S)-N-[(1S)-1-[5-(2-fluorophenyl)-1H-imidazol-2-yl]-7-(1,2-oxazol-3-yl)-7-oxoheptyl]-6-methyl-6-azaspiro[2.5]octane-2-carboxamide	IC50	0.1 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
CHEMBL6160900	IC50	0.104 nM
CHEMBL113303	IC50	0.11 nM
CHEMBL4644038	IC50	0.11 nM
CHEMBL4876610	IC50	0.11 nM
CHEMBL4878197	IC50	0.11 nM
2-(dimethylamino)-N-[(1S)-1-[5-(2-fluorophenyl)-1H-imidazol-2-yl]-7-(1,2-oxazol-3-yl)-7-oxoheptyl]acetamide	IC50	0.11 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
CHEMBL3622726	IC50	0.12 nM
(S)-N-(1-(4-chloro-2-(2-fluorophenyl)-1H-imidazol-5-yl)-7-(isoxazol-3-yl)-7-oxoheptyl)-1-methylazetidine-3-carboxamide	IC50	0.12 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
N-[(1S)-1-[5-(2-fluorophenyl)-1H-imidazol-2-yl]-7-(1,2-oxazol-3-yl)-7-oxoheptyl]-1-methylazetidine-2-carboxamide	IC50	0.13 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(S)-N-(7-(isoxazol-3-yl)-1-(5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl)-7-oxoheptyl)-1-methylazetidine-3-carboxamide	IC50	0.13 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
N-[(1S)-1-[4-chloro-2-(4-fluorophenyl)-1H-imidazol-5-yl]-7-(1,3-oxazol-2-yl)-7-oxoheptyl]-2-(dimethylamino)acetamide	IC50	0.14 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(1S)-6-ethyl-N-{(1S)-1-[5-(2- fluorophenyl)isoxazol-3-yl]-7- isoxazol-3-yl-7-oxoheptyl}-6- azaspiro[2.5]octane-1- carboxamide	IC50	0.14 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(S)-N-((S)-1-(4-chloro-5-(4- fluorophenyl)-1H-imidazol-2-yl)-7- (isoxazol-3-yl)-7-oxoheptyl)-6- methyl-6-azaspiro[2.5]octane-1- carboxamide 2,3- dihydroxysuccinate	IC50	0.14 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
4sc-202	IC50	0.16 nM
CHEMBL4637689	IC50	0.16 nM
CHEMBL5218660	IC50	0.16 nM
N-[(1S)-1-[5-(2-fluorophenyl)-1H-imidazol-2-yl]-7-(5-methyl-1,2-oxazol-3-yl)-7-oxoheptyl]-1-methylazetidine-3-carboxamide	IC50	0.16 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(S)-N-((S)-1-(4-cyano-2-(4- fluorophenyl)-1H-imidazol-5- yl)-7-(oxazol-2-yl)-7- oxoheptyl)-6-methyl-6- azaspiro[2.5]octane-1- carboxamide	IC50	0.16 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
CHEMBL4862152	IC50	0.17 nM
2-(dimethylamino)-N-[(1S)-1-[5-(2-fluorophenyl)-1H-imidazol-2-yl]-7-(5-methyl-1,2-oxazol-3-yl)-7-oxoheptyl]acetamide	IC50	0.18 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-(5-methyl-1,2-oxazol-3-yl)-7-oxoheptyl]-6-methyl-6-azaspiro[2.5]octane-2-carboxamide	IC50	0.18 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(S)-N-(7-(isoxazol-3-yl)-1-(5-(7-methoxy-2-methylquinolin-6-yl)oxazol-2-yl)-7-oxoheptyl)-1-methylazetidine-3-carboxamide	IC50	0.18 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(S)-N-((S)-7-(isoxazol-3-yl)-1-(5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl)-7-oxoheptyl)-6-methyl-6-azaspiro[2.5]octane-1-carboxamide	IC50	0.18 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(S)-N-(1-(4-chloro-5-(4- fluorophenyl)-1H-imidazol-2-yl)-7- (isoxazol-3-yl)-7-oxoheptyl)-1- methylazetidine-3-carboxamide 2,3-dihydroxysuccinate	IC50	0.18 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
CHEMBL4532398	IC50	0.19 nM
CHEMBL4642518	IC50	0.19 nM
(S)-N-(1-(4-cyano-2-(4- fluorophenyl)-1H-imidazol-5- yl)-7-(oxazol-2-yl)-7- oxoheptyl)thiazole-5- carboxamide	IC50	0.19 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
CHEMBL6145924	IC50	0.194 nM
(E)-N-hydroxy-3-[4-[[2-(1-methylindol-3-yl)ethylamino]methyl]phenyl]prop-2-enamide	IC50	0.2 nM	US-10188756: Imaging histone deacetylases with a radiotracer using positron emission tomography
CHEMBL3317812	IC50	0.2 nM
CHEMBL1793991	IC50	0.2 nM
CHEMBL4634501	IC50	0.2 nM
CHEMBL4780309	IC50	0.2 nM
CHEMBL4860000	IC50	0.2 nM
1-methyl-N-[(1S)-1-[5-(2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-(1,2-oxazol-3-yl)-7-oxoheptyl]azetidine-3-carboxamide	IC50	0.2 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
N-(1-(5-(2-fluorophenyl)oxazol-2-yl)-7-(isoxazol-3-yl)-7-oxoheptyl)-1-methylazetidine-3-carboxamide	IC50	0.2 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection
(S)-N-(1-(4-chloro-5-(4-fluorophenyl)-1H-imidazol-2-yl)-7-(isoxazol-3-yl)-7-oxoheptyl)-2-(dimethylamino)acetamide	IC50	0.2 nM	US-12331044: Inhibitors of histone deacetylase useful for the treatment or prevention of HIV infection

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
10.40	Ki	0.04	nM	CHEMBL5413269
10.22	IC50	0.06	nM	CHEMBL4860000
10.15	IC50	0.07	nM	CHEMBL4637689
10.10	IC50	0.08	nM	CHEMBL4862152
10.06	IC50	0.087	nM	CHEMBL4641682
10.03	IC50	0.093	nM	CHEMBL4649205
10.00	IC50	0.1	nM	CHEMBL4861467
10.00	Ki	0.1	nM	PANOBINOSTAT
9.89	IC50	0.13	nM	CHEMBL4878197
9.85	Ki	0.14	nM	TRICHOSTATIN
9.82	Ki	0.15	nM	ROMIDEPSIN
9.80	IC50	0.16	nM	CHEMBL4294949
9.77	IC50	0.17	nM	CHEMBL4634501
9.77	IC50	0.17	nM	CHEMBL5433552
9.76	IC50	0.1726	nM	CHEMBL4444219
9.74	IC50	0.18	nM	CHEMBL4644038
9.72	IC50	0.19	nM	CHEMBL4642518
9.70	IC50	0.2	nM	CHEMBL2371007
9.70	IC50	0.2	nM	CHEMBL4759693
9.70	IC50	0.2	nM	CHEMBL4742026
9.70	IC50	0.2	nM	CHEMBL4780309
9.70	IC50	0.2	nM	CHEMBL4753460
9.70	Ki	0.2	nM	CHEMBL99392
9.70	IC50	0.2	nM	CHEMBL5395502
9.70	IC50	0.2	nM	CHEMBL1793811
9.70	IC50	0.2	nM	CHEMBL1793991
9.70	IC50	0.2	nM	CHEMBL1793985
9.62	IC50	0.24	nM	CHEMBL4637357
9.59	IC50	0.2553	nM	CHEMBL4444219
9.59	Ki	0.26	nM	TRICHOSTATIN
9.59	Ki	0.26	nM	APICIDIN
9.55	IC50	0.28	nM	CHEMBL4444219
9.55	IC50	0.28	nM	CHEMBL4638264
9.55	IC50	0.28	nM	CHEMBL4597954
9.55	IC50	0.28	nM	CHEMBL5093099
9.52	IC50	0.3	nM	CHEMBL3329621
9.52	IC50	0.3	nM	CHEMBL2370998
9.52	IC50	0.3	nM	CHEMBL4761973
9.52	IC50	0.3	nM	CHEMBL4746782
9.52	IC50	0.3	nM	CHEMBL4745088
9.52	IC50	0.3	nM	CHEMBL5199116
9.52	IC50	0.3	nM	CHEMBL5170036
9.52	Ki	0.3	nM	CHEMBL279636
9.52	IC50	0.3	nM	CHEMBL4597954
9.52	IC50	0.3	nM	CHEMBL5796974
9.52	IC50	0.3	nM	CHEMBL1793822
9.50	IC50	0.316	nM	CHEMBL4444219
9.49	IC50	0.32	nM	CHEMBL4869000
9.48	IC50	0.33	nM	CHEMBL5218556
9.47	IC50	0.34	nM	CHEMBL4642023

PubChem BioAssay actives

2881 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
N-hydroxy-2-[4-(4-methylphenyl)sulfonylpiperazin-1-yl]-1,3-thiazole-5-carboxamide	1941741: Inhibition of HDAC (unknown origin)	ic50	0.0001	uM
N-[(1S)-1-[5-(2-fluorophenyl)-1H-imidazol-2-yl]-7-(1,2-oxazol-3-yl)-7-oxoheptyl]-1-methylazetidine-3-carboxamide	1664942: Inhibition of full length human recombinant FLAG-tagged HDAC3/His6-tagged SMRT (1 to 899 residues) expressed in HEK293F cells using FLUOR DE LYS as substrate preincubated for 3 hrs followed by substrate addition and measured after 60 mins by fluorescence based assay	ic50	0.0001	uM
(2S)-6-(cyclopropylmethyl)-N-[(1S)-1-[5-(2-methoxyquinolin-3-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-azaspiro[2.5]octane-2-carboxamide	1662502: Inhibition of HDAC3 (unknown origin)	ic50	0.0001	uM
(3S,6S)-6-(6-oxooctyl)-5,8,18,27,34-pentazahexacyclo[25.2.2.17,10.111,15.114,18.01,3]tetratriaconta-7,9,11(33),12,14,16-hexaene-4,32-dione	1754654: Inhibition of HDAC3 (unknown origin)	ic50	0.0001	uM
(3S,6S)-12-methoxy-6-(6-oxooctyl)-5,8,18,27,34-pentazahexacyclo[25.2.2.17,10.111,15.114,18.01,3]tetratriaconta-7,9,11,13,15(33),16-hexaene-4,32-dione	1754654: Inhibition of HDAC3 (unknown origin)	ic50	0.0001	uM
N-[(1S)-1-[5-(2-fluorophenyl)-1H-imidazol-2-yl]-7-(5-methyl-1,2-oxazol-3-yl)-7-oxoheptyl]-1-methylazetidine-3-carboxamide	1664942: Inhibition of full length human recombinant FLAG-tagged HDAC3/His6-tagged SMRT (1 to 899 residues) expressed in HEK293F cells using FLUOR DE LYS as substrate preincubated for 3 hrs followed by substrate addition and measured after 60 mins by fluorescence based assay	ic50	0.0001	uM
(2S)-6-(cyclopropylmethyl)-N-[(1S)-1-[5-(7-methoxyquinolin-6-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-azaspiro[2.5]octane-2-carboxamide	1768795: Inhibition of human recombinant FLAG-tagged HDAC3 expressed in HEK293F cells incubated for 30 mins by Fluor De Lys assay	ic50	0.0001	uM
(2S)-6-(cyclopropylmethyl)-N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1,3-oxazol-2-yl]-7-oxononyl]-6-azaspiro[2.5]octane-2-carboxamide	1768795: Inhibition of human recombinant FLAG-tagged HDAC3 expressed in HEK293F cells incubated for 30 mins by Fluor De Lys assay	ic50	0.0001	uM
N-[(1S)-1-[5-(2-fluorophenyl)-1,3-oxazol-2-yl]-7-(1,2-oxazol-3-yl)-7-oxoheptyl]-1-methylazetidine-3-carboxamide	1664942: Inhibition of full length human recombinant FLAG-tagged HDAC3/His6-tagged SMRT (1 to 899 residues) expressed in HEK293F cells using FLUOR DE LYS as substrate preincubated for 3 hrs followed by substrate addition and measured after 60 mins by fluorescence based assay	ic50	0.0002	uM
(2S)-N-[(1S)-1-[5-(2-methoxyquinolin-3-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-propan-2-yl-6-azaspiro[2.5]octane-2-carboxamide	1662502: Inhibition of HDAC3 (unknown origin)	ic50	0.0002	uM
(2S)-N-[(1S)-1-[5-(2-methoxyquinolin-3-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-methyl-6-azaspiro[2.5]octane-2-carboxamide	1662502: Inhibition of HDAC3 (unknown origin)	ic50	0.0002	uM
(E)-3-[4-[[2-(2-methyl-1H-indol-3-yl)ethylamino]methyl]phenyl]-N’-propylprop-2-enehydrazide;2,2,2-trifluoroacetic acid	1548756: Inhibition of recombinant human C-terminal GST/His-tagged HDAC3 (1 to 428 residues) co-expressed with human N-terminal GST-tagged NCOR2 (395 to 489 residues) in baculovirus infected Sf9 cells using Boc-Lys(acetyl)-AMC as substrate preincubated for 90 mins followed by substrate addition and measured after 2 hrs by fluorescence based microplate reader analysis	ic50	0.0002	uM
(2S)-6-ethyl-N-[(1S)-1-[5-(2-methoxyquinolin-3-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-azaspiro[2.5]octane-2-carboxamide	1726254: Inhibition of human recombinant full length FLAG-tagged HDAC3 expressed in HEK293F cells in using BML-KI104 as substrate in presence of SAHA as inhibitor preincubated for 3 hrs followed by addition of substrate measured after 30 mins by fluorescence based assay	ic50	0.0002	uM
(2S)-6-methyl-N-[(1S)-1-[5-(1-methylindol-3-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-azaspiro[2.5]octane-2-carboxamide	1694525: Inhibition of HDAC3 (unknown origin) using compound purified by traditional preparative HPLC work-flow	ic50	0.0002	uM
(2S)-N-[(1S)-1-[5-(5-chloro-2-methoxyphenyl)-1H-imidazol-2-yl]-7-oxononyl]-6-ethyl-6-azaspiro[2.5]octane-2-carboxamide	1694528: Inhibition of HDAC3 (unknown origin) using compound purified by microgram-scale HPLC work-flow	ic50	0.0002	uM
(2S)-6-ethyl-N-[(1S)-1-[5-(2-methoxy-5-propan-2-ylphenyl)-1H-imidazol-2-yl]-7-oxononyl]-6-azaspiro[2.5]octane-2-carboxamide	1694528: Inhibition of HDAC3 (unknown origin) using compound purified by microgram-scale HPLC work-flow	ic50	0.0002	uM
(2S)-N-[(1S)-1-[4-cyano-2-(2-methylquinolin-6-yl)-1H-imidazol-5-yl]-7-oxononyl]-6-methyl-6-azaspiro[2.5]octane-2-carboxamide	1674972: Inhibition of HDAC3 (unknown origin)	ic50	0.0002	uM
(2S)-N-[(1S)-1-[5-(9H-carbazol-3-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-methyl-6-azaspiro[2.5]octane-2-carboxamide	1694525: Inhibition of HDAC3 (unknown origin) using compound purified by traditional preparative HPLC work-flow	ic50	0.0002	uM
(2S)-6-ethyl-N-[(1S)-1-[5-(6-methoxy-2-methyl-2,3-dihydropyridin-5-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-azaspiro[2.5]octane-2-carboxamide	1694528: Inhibition of HDAC3 (unknown origin) using compound purified by microgram-scale HPLC work-flow	ic50	0.0002	uM
(2S)-6-ethyl-N-[(1S)-1-[5-(2-methoxy-5-methylphenyl)-1H-imidazol-2-yl]-7-oxononyl]-6-azaspiro[2.5]octane-2-carboxamide	1694528: Inhibition of HDAC3 (unknown origin) using compound purified by microgram-scale HPLC work-flow	ic50	0.0002	uM
7-[4-[[4-[3-(tert-butylsulfamoyl)anilino]-5-methylpyrimidin-2-yl]amino]-2-fluorophenoxy]-N-hydroxyheptanamide	2031064: Inhibition of HDAC in human HeLa cells nuclear extract incubated for 30 mins by multiplate reader analysis	ic50	0.0002	uM
7-[4-[[4-[3-(tert-butylsulfamoyl)anilino]-5-methylpyrimidin-2-yl]amino]phenoxy]-N-hydroxyheptanamide	2031064: Inhibition of HDAC in human HeLa cells nuclear extract incubated for 30 mins by multiplate reader analysis	ic50	0.0002	uM
(5R,8S,11S)-5-methyl-11-[(E)-4-[[(E)-4-[(5R,8S,11S)-5-methyl-6,9,13-trioxo-8-propan-2-yl-10-oxa-3,17-dithia-7,14,19,20-tetrazatricyclo[14.2.1.12,5]icosa-1(18),2(20),16(19)-trien-11-yl]but-3-enyl]disulfanyl]but-1-enyl]-8-propan-2-yl-10-oxa-3,17-dithia-7,14,19,20-tetrazatricyclo[14.2.1.12,5]icosa-1(18),2(20),16(19)-triene-6,9,13-trione	1188979: Inhibition of HDAC3 (unknown origin) incubated for 30 mins in presence of BSA and DTT by fluorescence assay	ic50	0.0003	uM
(3S,6R,9S,12R)-6,9-dimethyl-3-[6-[(2S)-oxiran-2-yl]-6-oxohexyl]-1,4,7,10-tetrazabicyclo[10.3.0]pentadecane-2,5,8,11-tetrone	1972771: Binding affinity to HDAC3 (unknown origin) assessed as inhibition constant	ki	0.0003	uM
(E)-3-[4-[[2-(2-methyl-1H-indol-3-yl)ethylamino]methyl]phenyl]-N’-propylprop-2-enehydrazide	1821182: Inhibition of human recombinant HDAC3 using Boc-Lys(acetyl)-AMC substrate incubated for 2 hrs by fluorescence based assay	ic50	0.0003	uM
(2S)-6-ethyl-N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-azaspiro[2.5]octane-2-carboxamide	1916029: Inhibition of human full length FLAG-tagged HDAC3 expressed in HEK293F cells using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay	ic50	0.0003	uM
(2S)-6-methyl-N-[(1S)-1-[5-(2-methyl-1-oxoisoquinolin-6-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-azaspiro[2.5]octane-2-carboxamide	1754654: Inhibition of HDAC3 (unknown origin)	ic50	0.0003	uM
(2S)-6-cyclobutyl-N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-azaspiro[2.5]octane-2-carboxamide	1916029: Inhibition of human full length FLAG-tagged HDAC3 expressed in HEK293F cells using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay	ic50	0.0003	uM
(2S)-N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1,3-oxazol-2-yl]-7-oxononyl]-6-methyl-6-azaspiro[2.5]octane-2-carboxamide	1916029: Inhibition of human full length FLAG-tagged HDAC3 expressed in HEK293F cells using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay	ic50	0.0003	uM
(3S,6S)-6-(6-oxooctyl)-22-oxa-5,8,18,26,33-pentazahexacyclo[24.2.2.17,10.111,15.114,18.01,3]tritriaconta-7,9,11(32),12,14,16-hexaene-4,31-dione	1754654: Inhibition of HDAC3 (unknown origin)	ic50	0.0003	uM
(3S)-7-ethyl-N-[(1S)-1-[5-(2-methoxyquinolin-3-yl)-1H-imidazol-2-yl]-7-oxononyl]-7-azaspiro[3.5]nonane-3-carboxamide	1662502: Inhibition of HDAC3 (unknown origin)	ic50	0.0003	uM
(2S)-6-(dimethylamino)-N-[(1S)-1-[5-(2-methoxyquinolin-3-yl)-1H-imidazol-2-yl]-7-oxononyl]spiro[2.5]octane-2-carboxamide	1662502: Inhibition of HDAC3 (unknown origin)	ic50	0.0003	uM
(2S)-6-methyl-N-[(1S)-1-[5-(2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-azaspiro[2.5]octane-2-carboxamide	1916029: Inhibition of human full length FLAG-tagged HDAC3 expressed in HEK293F cells using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay	ic50	0.0003	uM
(2S)-6-ethyl-N-[(1S)-1-[5-(7-methoxy-1-methyl-2-oxoquinolin-6-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-azaspiro[2.5]octane-2-carboxamide	1916029: Inhibition of human full length FLAG-tagged HDAC3 expressed in HEK293F cells using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay	ic50	0.0003	uM
(2S)-N-[(1S)-1-[5-(7-fluoro-2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-methyl-6-azaspiro[2.5]octane-2-carboxamide	1916029: Inhibition of human full length FLAG-tagged HDAC3 expressed in HEK293F cells using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay	ic50	0.0003	uM
(2S)-N-[(1S)-1-[5-(2-ethylquinolin-6-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-methyl-6-azaspiro[2.5]octane-2-carboxamide	1916029: Inhibition of human full length FLAG-tagged HDAC3 expressed in HEK293F cells using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay	ic50	0.0003	uM
(2S)-6-methyl-N-[(1S)-7-oxo-1-(5-quinolin-3-yl-1H-imidazol-2-yl)nonyl]-6-azaspiro[2.5]octane-2-carboxamide	1694528: Inhibition of HDAC3 (unknown origin) using compound purified by microgram-scale HPLC work-flow	ic50	0.0003	uM
(2S)-6-(cyclopropylmethyl)-N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-azaspiro[2.5]octane-2-carboxamide	1916029: Inhibition of human full length FLAG-tagged HDAC3 expressed in HEK293F cells using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay	ic50	0.0003	uM
(2S)-6-ethyl-N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1,3-oxazol-2-yl]-7-oxononyl]-6-azaspiro[2.5]octane-2-carboxamide	1916029: Inhibition of human full length FLAG-tagged HDAC3 expressed in HEK293F cells using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay	ic50	0.0003	uM
(2S)-N-[(1S)-1-[5-(7-methoxy-2-methylquinolin-6-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-propan-2-yl-6-azaspiro[2.5]octane-2-carboxamide	1916029: Inhibition of human full length FLAG-tagged HDAC3 expressed in HEK293F cells using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay	ic50	0.0003	uM
(2S)-N-[(1S)-1-[5-(2-cyclopropylquinolin-6-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-methyl-6-azaspiro[2.5]octane-2-carboxamide	1916029: Inhibition of human full length FLAG-tagged HDAC3 expressed in HEK293F cells using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay	ic50	0.0003	uM
(2S)-N-[(1S)-1-[5-(2,7-dimethylquinolin-6-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-methyl-6-azaspiro[2.5]octane-2-carboxamide	1916029: Inhibition of human full length FLAG-tagged HDAC3 expressed in HEK293F cells using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay	ic50	0.0003	uM
(2S)-N-[(1S)-1-[5-(2-cyclopropyl-7-methoxyquinolin-6-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-methyl-6-azaspiro[2.5]octane-2-carboxamide	1916029: Inhibition of human full length FLAG-tagged HDAC3 expressed in HEK293F cells using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay	ic50	0.0003	uM
(2S)-N-[(1S)-1-[4-cyano-2-(4-pyridin-3-ylphenyl)-1H-imidazol-5-yl]-7-oxononyl]-6-methyl-6-azaspiro[2.5]octane-2-carboxamide	1674972: Inhibition of HDAC3 (unknown origin)	ic50	0.0003	uM
(2S)-N-[(1S)-1-[4-cyano-2-(2-methylindazol-5-yl)-1H-imidazol-5-yl]-7-oxononyl]-6-methyl-6-azaspiro[2.5]octane-2-carboxamide	1674972: Inhibition of HDAC3 (unknown origin)	ic50	0.0003	uM
5-methoxy-N-[[4-(propylaminocarbamoyl)phenyl]methyl]-1-benzofuran-2-carboxamide	1821182: Inhibition of human recombinant HDAC3 using Boc-Lys(acetyl)-AMC substrate incubated for 2 hrs by fluorescence based assay	ic50	0.0003	uM
(9S,12R)-3-[(2S)-butan-2-yl]-9-(6-hydroxy-5-oxoheptyl)-6-[(1-methoxyindol-3-yl)methyl]-1,4,7,10-tetrazabicyclo[10.4.0]hexadecane-2,5,8,11-tetrone	1847765: Inhibition of HDAC (unknown origin)	ic50	0.0003	uM
(9S,12R)-3-[(2S)-butan-2-yl]-6-(1H-indol-3-ylmethyl)-9-(5-oxoheptyl)-1,4,7,10-tetrazabicyclo[10.4.0]hexadecane-2,5,8,11-tetrone	1847765: Inhibition of HDAC (unknown origin)	ic50	0.0003	uM
(2S)-N-[(1S)-1-[5-(2-cyclopropyl-7-methoxyquinolin-6-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-(cyclopropylmethyl)-6-azaspiro[2.5]octane-2-carboxamide	1916029: Inhibition of human full length FLAG-tagged HDAC3 expressed in HEK293F cells using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay	ic50	0.0003	uM
(2S)-6-(cyclopropylmethyl)-N-[(1S)-1-[5-(2-ethyl-7-methoxyquinolin-6-yl)-1H-imidazol-2-yl]-7-oxononyl]-6-azaspiro[2.5]octane-2-carboxamide	1916029: Inhibition of human full length FLAG-tagged HDAC3 expressed in HEK293F cells using BML-KI104 as substrate preincubated for 3 hrs followed by substrate addition measured after 60 mins by modified FLUOR DE LYS assay	ic50	0.0003	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
trichostatin A	affects binding, affects cotreatment, decreases reaction, increases reaction, affects expression (+2 more)	6
sodium arsenite	decreases expression, decreases reaction, increases expression	3
Vorinostat	decreases activity, affects binding, decreases expression	3
bisphenol A	affects expression, decreases expression	2
manganese chloride	increases expression, decreases reaction, affects binding, increases abundance, increases reaction	2
Air Pollutants	decreases expression, affects expression, increases abundance	2
Butyrates	decreases activity, increases expression	2
Estradiol	decreases reaction, increases expression, decreases expression	2
Valproic Acid	decreases activity, increases expression	2
RGFP966	decreases activity	1
aminomethylphosphonic acid (AMPA)	increases expression	1
methylmercuric chloride	increases expression	1
triphenyl phosphate	affects expression	1
honokiol	decreases expression, decreases reaction, increases reaction, decreases activity, affects binding (+1 more)	1
polymarcine	decreases activity	1
mancozeb	decreases activity	1
methoxyacetic acid	decreases activity	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
afimoxifene	affects binding, increases reaction	1
sulforaphane	affects cotreatment, decreases expression	1
tanshinone	increases expression	1
benzamide	decreases activity	1
di-n-butylphosphoric acid	affects expression	1
trapoxin B	decreases activity	1
4-phenylbutyric acid	decreases expression, decreases reaction	1
15-deoxy-delta(12,14)-prostaglandin J2	decreases expression	1
monomethylarsonous acid	increases expression	1
polyphenon E	decreases expression, increases reaction	1
ICG 001	decreases expression	1
mocetinostat	decreases expression	1

ChEMBL screening assays

2753 unique, capped per target: 2724 binding, 23 admet, 5 functional, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1002515	Binding	Inhibition of human C-terminal FLAG-tagged HDAC3 in HEK293 cells	Discovery of a potent class I selective ketone histone deacetylase inhibitor with antitumor activity in vivo and optimized pharmacokinetic properties. — *J Med Chem*
CHEMBL3860978	ADMET	Inhibition of HDAC3 (unknown origin)	Design, Synthesis, and Biological Evaluation of First-in-Class Dual Acting Histone Deacetylases (HDACs) and Phosphodiesterase 5 (PDE5) Inhibitors for the Treatment of Alzheimer’s Disease. — *J Med Chem*
CHEMBL5723165	Functional	Affinity Biochemical interaction: (detection of AMC fluorescence generated by tryptic cleavage of deacetylated peptide Ac-NH-GGK(Ac)-AMC, enzymatic assay) EUB0002304aCl HDAC3	Affinity Biochemical Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

3 cell lines: 2 embryonic stem cell, 1 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A2M3	SEES3-1V human HDAC3, clone1	Embryonic stem cell	Male
CVCL_A2M4	SEES3-1V human HDAC3, clone2	Embryonic stem cell	Male
CVCL_SR08	HAP1 HDAC3 (-)	Cancer cell line	Male

Clinical trials (associated diseases)

Via MONDO — disease-level, not drug-specific.

showing 60 of 312 trials:

NCT	Phase	Status	Title
NCT04586348	Phase 4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	Phase 4	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,
NCT02559102	Phase 3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	Phase 3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	Phase 3	RECRUITING	Reducing Missed Appointments
NCT07377032	Phase 3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT00517959	Phase 3	UNKNOWN	SCRT Versus Conventional RT in Children and Young Adults With Low Grade and Benign Brain Tumors
NCT01096368	Phase 3	COMPLETED	Maintenance Chemotherapy or Observation Following Induction Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Ependymoma
NCT02909959	Phase 2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	Phase 2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	Phase 2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00003479	Phase 2	TERMINATED	Antineoplaston Therapy in Treating Patients With Ependymoma
NCT00520936	Phase 2	COMPLETED	A Study of Pemetrexed in Children With Recurrent Cancer
NCT00840047	Phase 2	ACTIVE_NOT_RECRUITING	Methionine PET/CT Studies In Patients With Cancer
NCT01088035	Phase 2	TERMINATED	Carboplatin as a Radiosensitizer in Treating Childhood Ependymoma
NCT01247922	Phase 2	TERMINATED	Single-agent Erlotinib in Patients Previously Treated With Oral Etoposide in Protocol OSI-774-205
NCT01288235	Phase 2	COMPLETED	Proton Radiotherapy for Pediatric Brain Tumors Requiring Partial Brain Irradiation
NCT01295944	Phase 2	COMPLETED	Carboplatin and Bevacizumab for Recurrent Ependymoma
NCT01356290	Phase 2	RECRUITING	Antiangiogenic Therapy for Children With Recurrent Medulloblastoma, Ependymoma, ATRT and Rare CNS Tumors
NCT01836549	Phase 2	TERMINATED	Imetelstat Sodium in Treating Younger Patients With Recurrent or Refractory Brain Tumors
NCT02125786	Phase 2	ACTIVE_NOT_RECRUITING	A Trial of Surgery and Fractionated Re-Irradiation for Recurrent Ependymoma
NCT02689336	Phase 2	WITHDRAWN	Erlotinib in Combination With Temozolomide in Treating Relapsed/Recurrent/Refractory Pediatric Solid Tumors
NCT03095248	Phase 2	TERMINATED	Trial of Selumetinib in Patients With Neurofibromatosis Type II Related Tumors
NCT03155620	Phase 2	ACTIVE_NOT_RECRUITING	Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders (The Pediatric MATCH Screening Trial)
NCT03173950	Phase 2	TERMINATED	Immune Checkpoint Inhibitor Nivolumab in People With Recurrent Select Rare CNS Cancers
NCT03194906	Phase 2	COMPLETED	Memantine for Prevention of Cognitive Late Effects in Pediatric Patients Receiving Cranial Radiation Therapy for Localized Brain Tumors
NCT03210714	Phase 2	ACTIVE_NOT_RECRUITING	Erdafitinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With FGFR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213652	Phase 2	ACTIVE_NOT_RECRUITING	Ensartinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With ALK or ROS1 Genomic Alterations (A Pediatric MATCH Treatment Trial)
NCT03213665	Phase 2	COMPLETED	Tazemetostat in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With EZH2, SMARCB1, or SMARCA4 Gene Mutations (A Pediatric MATCH Treatment Trial)
NCT03213678	Phase 2	COMPLETED	Samotolisib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With TSC or PI3K/MTOR Mutations (A Pediatric MATCH Treatment Trial)
NCT03213704	Phase 2	ACTIVE_NOT_RECRUITING	Larotrectinib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With NTRK Fusions (A Pediatric MATCH Treatment Trial)
NCT03220035	Phase 2	COMPLETED	Vemurafenib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With BRAF V600 Mutations (A Pediatric MATCH Treatment Trial)
NCT03233204	Phase 2	COMPLETED	Olaparib in Treating Patients With Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Defects in DNA Damage Repair Genes (A Pediatric MATCH Treatment Trial)
NCT03526250	Phase 2	COMPLETED	Palbociclib in Treating Patients With Relapsed or Refractory Rb Positive Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With Activating Alterations in Cell Cycle Genes (A Pediatric MATCH Treatment Trial)
NCT03698994	Phase 2	ACTIVE_NOT_RECRUITING	Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial)
NCT03727841	Phase 2	TERMINATED	Marizomib for Recurrent Low-Grade and Anaplastic Supratentorial, Infratentorial, and Spinal Cord Ependymoma
NCT04049669	Phase 2	ACTIVE_NOT_RECRUITING	Pediatric Trial of Indoximod With Chemotherapy and Radiation for Relapsed Brain Tumors or Newly Diagnosed DIPG
NCT04195555	Phase 2	ACTIVE_NOT_RECRUITING	Ivosidenib in Treating Patients With Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With IDH1 Mutations (A Pediatric MATCH Treatment Trial)
NCT04284774	Phase 2	ACTIVE_NOT_RECRUITING	Tipifarnib for the Treatment of Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With HRAS Gene Alterations, a Pediatric MATCH Treatment Trial
NCT04320888	Phase 2	ACTIVE_NOT_RECRUITING	Selpercatinib for the Treatment of Advanced Solid Tumors, Lymphomas, or Histiocytic Disorders With Activating RET Gene Alterations, a Pediatric MATCH Treatment Trial
NCT04374305	Phase 2	RECRUITING	Innovative Trial for Understanding the Impact of Targeted Therapies in NF2-Related Schwannomatosis (INTUITT-NF2)
NCT04743661	Phase 2	ACTIVE_NOT_RECRUITING	131I-Omburtamab, in Recurrent Medulloblastoma and Ependymoma
NCT06804655	Phase 2	RECRUITING	Pharmacoscopy for Patients With Refractory Primary Brain Tumors
NCT07424092	Phase 2	RECRUITING	Intratumoral DNX-2401 for High Grade Pediatric Brain Tumors
NCT07707947	Phase 2	NOT_YET_RECRUITING	Selumetinib for NF2-Related Schwannomatosis
NCT07713745	Phase 2	NOT_YET_RECRUITING	Platform Research for Innovative Medicines in NF2-SWN (PRIME-NF2)
NCT00503191	Phase 1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	Phase 1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
NCT06300398	Phase 1	COMPLETED	IAMA-6 Oral Dose Study in Healthy Adults
NCT00634231	Phase 1	COMPLETED	A Phase I Study of AdV-tk + Prodrug Therapy in Combination With Radiation Therapy for Pediatric Brain Tumors
NCT00994071	Phase 1	COMPLETED	A Phase I Study of ABT-888, an Oral Inhibitor of Poly(ADP-ribose) Polymerase and Temozolomide in Children With Recurrent/Refractory CNS Tumors
NCT01171469	Phase 1	COMPLETED	Vaccination With Dendritic Cells Loaded With Brain Tumor Stem Cells for Progressive Malignant Brain Tumor
NCT01331135	Phase 1	COMPLETED	Aflac ST0901 CHOANOME - Sirolimus in Solid Tumors
NCT01498783	Phase 1	COMPLETED	Phase I Study of 5-Fluorouracil in Children and Young Adults With Recurrent Ependymoma
NCT01795313	Phase 1	TERMINATED	Immunotherapy for Recurrent Ependymomas in Children Using Tumor Antigen Peptides With Imiquimod
NCT02271711	Phase 1	COMPLETED	Expanded Natural Killer Cell Infusion in Treating Younger Patients With Recurrent/Refractory Brain Tumors
NCT02359565	Phase 1	ACTIVE_NOT_RECRUITING	Pembrolizumab in Treating Younger Patients With Recurrent, Progressive, or Refractory High-Grade Gliomas, Diffuse Intrinsic Pontine Gliomas, Hypermutated Brain Tumors, Ependymoma or Medulloblastoma
NCT02502708	Phase 1	COMPLETED	Study of the IDO Pathway Inhibitor, Indoximod, and Temozolomide for Pediatric Patients With Progressive Primary Malignant Brain Tumors
NCT02722512	Phase 1	TERMINATED	Trial of Heat Shock Protein Peptide Complex-96 (HSPPC-96) Vaccine
NCT03043391	Phase 1	COMPLETED	Phase 1b Study PVSRIPO for Recurrent Malignant Glioma in Children

Predicted chemistry — Sugi Predict

The predicted patent-compound landscape for HDAC3 across ~30M SureChEMBL compounds — explore on Sugi Predict.