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 — 2 likely-pathogenic
• Druggable target: yes — 37 molecules with ChEMBL bioactivity
• Cancer dependency (DepMap): dependent in 95.1% of screened cell lines (common-essential)
• Transcription factor: yes — 27 downstream targets (CollecTRI)
• MANE Select transcript: NM_003883

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: 31 — 17 protein_coding, 11 retained_intron, 2 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

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

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.

FANTOM5 promoters (2 alternative TSS)

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

Top tissues by expression

299 total, 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

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

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)

27 targeting HDAC3, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-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

DepMap (CRISPR cell-line fitness): dependent in 95.1% of screened cell lines, common-essential.

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)

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), 6 shown:

• 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 (56 total): helix 16, 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.

PDB	Method	Resolution (Å)
4A69	X-RAY DIFFRACTION	2.06

Predicted structure (AlphaFold)

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

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): 135

Ligand- & substrate-binding residues (7): 172; 259; 265; 17; 21; 25; 170

Post-translational modifications (1): 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

25 pathways

ID	Pathway
R-HSA-193670	p75NTR negatively regulates cell cycle via SC1
R-HSA-1989781	PPARA activates gene expression
R-HSA-2122947	NOTCH1 Intracellular Domain Regulates Transcription
R-HSA-2151201	Transcriptional activation of mitochondrial biogenesis
R-HSA-2644606	Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-2894862	Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-3214815	HDACs deacetylate histones
R-HSA-350054	Notch-HLH transcription pathway
R-HSA-381340	Transcriptional regulation of white adipocyte differentiation
R-HSA-390471	Association of TriC/CCT with target proteins during biosynthesis
R-HSA-400206	Regulation of lipid metabolism by PPARalpha
R-HSA-5617472	Activation of anterior HOX genes in hindbrain development during early embryogenesis
R-HSA-8940973	RUNX2 regulates osteoblast differentiation
R-HSA-8943724	Regulation of PTEN gene transcription
R-HSA-9022537	Loss of MECP2 binding ability to the NCoR/SMRT complex
R-HSA-9022692	Regulation of MECP2 expression and activity
R-HSA-9029569	NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux
R-HSA-9609690	HCMV Early Events
R-HSA-9701898	STAT3 nuclear events downstream of ALK signaling
R-HSA-9707564	Cytoprotection by HMOX1
R-HSA-9707616	Heme signaling
R-HSA-9841922	MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis
R-HSA-9931509	Expression of BMAL (ARNTL), CLOCK, and NPAS2
R-HSA-9933387	RORA,B,C and NR1D1 (REV-ERBA) regulate gene expression
R-HSA-9976102	Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)

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 (44): 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), transcription by RNA polymerase II (GO:0006366), protein deacetylation (GO:0006476), regulation of mitotic cell cycle (GO:0007346), 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), regulation of multicellular organism growth (GO:0040014), 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), random inactivation of X chromosome (GO:0060816), neural precursor cell proliferation (GO:0061351), 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), negative regulation of cardiac muscle cell differentiation (GO:2000726)

GO Molecular Function (23): 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), deacetylase activity (GO:0019213)

GO Cellular Component (11): histone deacetylase complex (GO:0000118), chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), cytoplasm (GO:0005737), Golgi apparatus (GO:0005794), cytosol (GO:0005829), plasma membrane (GO:0005886), transcription repressor complex (GO:0017053), mitotic spindle (GO:0072686), chromosome (GO:0005694)

Reactome top-level categories

Rollup of top-20 pathways:

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

GO top-level categories

Rollup of top GO terms by namespace:

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
mitotic cell cycle	2
circadian rhythm	2
regulation of gene expression	2
protein binding	2
catalytic activity, acting on a protein	2
enzyme binding	2
intracellular membrane-bounded organelle	2
cytoplasm	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	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
DNA-templated transcription	1
protein deacylation	1
regulation of cell cycle	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

Protein interactions and networks

STRING

3306 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HDAC3	NCOR1	O75376	997
HDAC3	NCOR2	Q9Y618	995
HDAC3	TBL1X	O60907	994
HDAC3	TBL1Y	Q9BQ87	994
HDAC3	TBL1XR1	Q9BZK7	991
HDAC3	EZH2	Q15910	954
HDAC3	GPS2	Q13227	944
HDAC3	EMD	P50402	919
HDAC3	RBBP4	P31149	908
HDAC3	MORF4L1	Q9UBU8	893
HDAC3	SIN3A	Q96ST3	887
HDAC3	NR1D1	P20393	826
HDAC3	FOXO3	O43524	824
HDAC3	SIRT2	Q8IXJ6	814
HDAC3	SUDS3	Q9H7L9	808

IntAct

243 interactions, top by confidence:

A	B	Type	Score
NCOR2	HDAC3	psi-mi:“MI:0407”(direct interaction)	0.950
HDAC3	NCOR2	psi-mi:“MI:0407”(direct interaction)	0.950
HDAC3	NCOR2	psi-mi:“MI:0915”(physical association)	0.950
NCOR2	HDAC3	psi-mi:“MI:0915”(physical association)	0.950
GPS2	HDAC3	psi-mi:“MI:0915”(physical association)	0.900
GPS2	HDAC3	psi-mi:“MI:0914”(association)	0.900
HDAC3	NCOR1	psi-mi:“MI:0915”(physical association)	0.800
HDAC3	TBL1X	psi-mi:“MI:0914”(association)	0.760
CCT2	TXNDC9	psi-mi:“MI:0914”(association)	0.730
HDAC3	AKAP8	psi-mi:“MI:0914”(association)	0.650
AKAP8	HDAC3	psi-mi:“MI:0914”(association)	0.650
HDAC3	AKAP8	psi-mi:“MI:0915”(physical association)	0.650
AKAP8	HDAC3	psi-mi:“MI:0403”(colocalization)	0.650
HDAC3	AKAP8	psi-mi:“MI:0403”(colocalization)	0.650
HDAC3	KDM1A	psi-mi:“MI:0914”(association)	0.650
TBL1XR1	HDAC3	psi-mi:“MI:0914”(association)	0.640
CCT3	TXNDC9	psi-mi:“MI:0914”(association)	0.640
CCT5	TXNDC9	psi-mi:“MI:0914”(association)	0.640

BioGRID (663): HDAC3 (Affinity Capture-Western), HDAC3 (Affinity Capture-Western), HDAC3 (Affinity Capture-Western), HDAC3 (Affinity Capture-Western), PPARG (Affinity Capture-Western), PPARG (Biochemical Activity), HDAC3 (Reconstituted Complex), DDX5 (Affinity Capture-Western), DDX17 (Affinity Capture-Western), APEX1 (Affinity Capture-Western), HDAC3 (Affinity Capture-Western), HDAC3 (Reconstituted Complex), HDAC3 (Reconstituted Complex), HDAC3 (Reconstituted Complex), HDAC3 (Reconstituted Complex)

ESM2 similar proteins: A0A0K0JFP3, O09106, O13298, O13648, O15379, O17695, O22446, O42227, O59702, O74429, O88895, P32561, P53096, P53973, P56517, P56518, P56519, P56520, P56521, P56523, P70288, Q09440, Q13547, Q20296, Q28DV3, Q32PJ8, Q4QQW4, Q4SFA0, Q55BW2, Q55FN5, Q5RAG0, Q5RB76, Q61E36, Q6IRL9, Q6P6W3, Q6YV04, Q7Y0Y6, Q7Y0Y8, Q803C3, Q8H0W2

Diamond homologs: B1H369, B1WC68, O09106, O13298, O15379, O17695, O22446, O30107, O42227, O59702, O88895, P32561, P39067, P53096, P56517, P56518, P56519, P56520, P56521, P56524, P70288, P83038, Q02959, Q09440, Q0VCB2, Q12214, Q13547, Q28DV3, Q32PJ8, Q3JUN4, Q4QQW4, Q4SFA0, Q54X15, Q55BW2, Q55FN5, Q5R902, Q5RAG0, Q5RB76, Q6GPA7, Q6IRL9

SIGNOR signaling

52 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”

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 152 IntAct physical interaction partners (hypergeometric vs the genome-wide background, BH-FDR, gene-set size 15–500, ranked by fold). A functional readout of the neighbourhood — distinct from this gene’s own memberships above, and biased toward well-studied / hub proteins, so read it as themes rather than proof.

Reactome pathways:

Pathway	Partners	Fold	FDR
Notch-HLH transcription pathway	9	36.0×	4e-10
NOTCH1 Intracellular Domain Regulates Transcription	11	25.7×	2e-10
Regulation of MECP2 expression and activity	7	25.3×	5e-07
Transcriptional Regulation by MECP2	7	21.8×	1e-06
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	6	21.7×	1e-05
Downregulation of SMAD2/3:SMAD4 transcriptional activity	6	21.7×	1e-05
Constitutive Signaling by NOTCH1 PEST Domain Mutants	11	21.2×	4e-10
Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants	11	21.2×	4e-10

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of miRNA transcription	8	17.2×	5e-06
negative regulation of gene expression, epigenetic	5	14.9×	2e-03
cellular response to UV	5	10.9×	5e-03
heterochromatin formation	5	9.5×	9e-03
epidermal growth factor receptor signaling pathway	5	9.2×	9e-03
somatic stem cell population maintenance	5	9.2×	9e-03
negative regulation of transforming growth factor beta receptor signaling pathway	7	9.0×	1e-03
cellular response to hypoxia	8	7.2×	2e-03

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

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

Top pathogenic / likely-pathogenic (2)

Variant ID	HGVS	Classification
520683	NM_003883.4(HDAC3):c.902G>A (p.Arg301Gln)	Likely pathogenic
521540	NM_003883.4(HDAC3):c.893A>G (p.Tyr298Cys)	Likely pathogenic

SpliceAI

2053 predictions. Top by Δscore:

Variant	Effect	Δscore
5:141621439:T:TA	donor_gain	1.0000
5:141621487:T:A	donor_gain	1.0000
5:141625194:C:A	donor_gain	1.0000
5:141625203:CAGA:C	donor_loss	1.0000
5:141625204:AGAC:A	donor_loss	1.0000
5:141625205:GAC:G	donor_loss	1.0000
5:141625207:C:CA	donor_loss	1.0000
5:141625225:AGGAC:A	donor_gain	1.0000
5:141625235:T:A	donor_gain	1.0000
5:141625257:T:TA	donor_gain	1.0000
5:141625361:AGATA:A	acceptor_gain	1.0000
5:141625362:GATA:G	acceptor_gain	1.0000
5:141625364:TA:T	acceptor_gain	1.0000
5:141625366:C:CC	acceptor_gain	1.0000
5:141625370:T:C	acceptor_gain	1.0000
5:141625370:T:TC	acceptor_gain	1.0000
5:141625666:G:C	donor_gain	1.0000
5:141625765:C:CC	acceptor_gain	1.0000
5:141625766:T:C	acceptor_gain	1.0000
5:141627895:ATGC:A	donor_gain	1.0000
5:141627956:CA:C	acceptor_gain	1.0000
5:141628553:A:AC	donor_gain	1.0000
5:141628554:C:CC	donor_gain	1.0000
5:141628554:CTTA:C	donor_gain	1.0000
5:141628555:TTAC:T	donor_loss	1.0000
5:141628557:A:AC	donor_gain	1.0000
5:141628557:A:T	donor_loss	1.0000
5:141628557:ACT:A	donor_gain	1.0000
5:141628558:C:CG	donor_gain	1.0000
5:141628558:CT:C	donor_gain	1.0000

AlphaMissense

2864 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
5:141625694:G:C	N350K	1.000
5:141625694:G:T	N350K	1.000
5:141625748:A:C	F332L	1.000
5:141625748:A:T	F332L	1.000
5:141625750:A:G	F332L	1.000
5:141626195:A:G	W307R	1.000
5:141626195:A:T	W307R	1.000
5:141626196:G:C	C306W	1.000
5:141626200:C:G	R305P	1.000
5:141626203:G:T	A304D	1.000
5:141626222:A:G	Y298H	1.000
5:141626224:C:A	G297V	1.000
5:141626224:C:T	G297D	1.000
5:141626225:C:A	G297C	1.000
5:141626225:C:G	G297R	1.000
5:141626227:C:A	G296V	1.000
5:141626227:C:T	G296D	1.000
5:141626228:C:G	G296R	1.000
5:141626230:C:A	G295V	1.000
5:141626230:C:T	G295D	1.000
5:141626231:C:G	G295R	1.000
5:141626233:C:A	G294V	1.000
5:141626233:C:T	G294D	1.000
5:141626234:C:G	G294R	1.000
5:141627911:A:G	L271P	1.000
5:141627923:C:A	G267V	1.000
5:141627923:C:T	G267D	1.000
5:141627924:C:G	G267R	1.000
5:141627926:A:G	L266S	1.000
5:141627932:T:A	D264V	1.000

dbSNP variants (sampled 300 via entrez): RS1000129847 (5:141627537 C>A,T), RS1000388630 (5:141634628 C>G,T), RS1000405355 (5:141635653 TCAACTCAGG>T), RS1000437456 (5:141627344 T>C), RS1000491299 (5:141627095 A>G), RS1000556975 (5:141629984 G>A,C), RS1000738666 (5:141635114 G>A,C,T), RS1001125584 (5:141633292 T>G), RS1001189800 (5:141635758 C>T), RS1001317430 (5:141628921 A>G), RS1001552013 (5:141634344 G>A), RS1001569293 (5:141636124 C>T), RS1001665366 (5:141626610 C>T), RS1001821913 (5:141634014 T>C), RS1001951669 (5:141624937 A>G)

Disease associations

OMIM: gene MIM:605166 | disease phenotypes:

GenCC curated gene-disease

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

Mondo (3): ependymoma (MONDO:0016698), complex neurodevelopmental disorder (MONDO:0100038), neurodevelopmental disorder (MONDO:0700092)

Orphanet (1): Ependymoma (Orphanet:251636)

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010002_39	Refractive error	2.000000e-14

MeSH disease descriptors (2)

Descriptor	Name	Tree numbers
D004806	Ependymoma	C04.557.465.625.600.380.290; C04.557.470.670.380.290; C04.557.580.625.600.380.290
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)

Molecules with ChEMBL bioactivity

37 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 858,754 (via chembl_molecule»patent_compound — counts attach to the compound, not the gene–compound relationship, so off-target/promiscuous molecules can dominate).

Molecule	Name	Phase	Patents
CHEMBL1213492	GIVINOSTAT	4	2,827
CHEMBL325041	BORTEZOMIB	4	13,120
CHEMBL343448	ROMIDEPSIN	4	12,963
CHEMBL408513	BELINOSTAT	4	7,765
CHEMBL483254	PANOBINOSTAT	4	11,666
CHEMBL487253	BENDAMUSTINE	4	30,877
CHEMBL98	VORINOSTAT	4	50,361
CHEMBL118	CELECOXIB	4	112,844
CHEMBL1469	PHENYLBUTANOIC ACID	4	37,081
CHEMBL1746	SODIUM PHENYLBUTYRATE	4	5,577
CHEMBL1851943	PRACINOSTAT	3	1,998
CHEMBL2103863	ABEXINOSTAT	3	2,195
CHEMBL235191	TACEDINALINE	3	2,950
CHEMBL27759	ENTINOSTAT	3	6,584
CHEMBL3621988	TUCIDINOSTAT	3	2,182
CHEMBL140	CURCUMIN	3	93,882
CHEMBL145	CAFFEIC ACID	3	36,305
CHEMBL14227	BUTYRIC ACID	2	424,980
CHEMBL1801250	NANATINOSTAT	2	754
CHEMBL2105763	QUISINOSTAT	2	1,843
CHEMBL2364628	RICOLINOSTAT	2
CHEMBL272980	MOCETINOSTAT	2
CHEMBL356066	DACINOSTAT	2
CHEMBL3622533	FIMEPINOSTAT	2
CHEMBL3693786	CITARINOSTAT	2
CHEMBL3989941	TINOSTAMUSTINE	2
CHEMBL4283683	DOMATINOSTAT	2
CHEMBL62381	SODIUM BUTYRATE	2
CHEMBL191482	AR-42	2
CHEMBL284616	CHLOROGENIC ACID	2

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — 3.5.1.- 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)

658 measured of 824 human assays (825 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
(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
(E)-3-[4-[[1-adamantylmethyl(methyl)amino]methyl]phenyl]-N-hydroxyprop-2-enamide	IC50	0.3 nM	US-10188756: Imaging histone deacetylases with a radiotracer using positron emission tomography
(E)-3-[4-[(1-adamantylmethylamino)methyl]-3-fluorophenyl]-N-hydroxyprop-2-enamide	IC50	0.78 nM	US-10188756: Imaging histone deacetylases with a radiotracer using positron emission tomography
(E)-3-[4-[[1-adamantylmethyl(methyl)amino]methyl]-3-fluorophenyl]-N-hydroxyprop-2-enamide	IC50	0.78 nM	US-10188756: Imaging histone deacetylases with a radiotracer using positron emission tomography
N-hydroxy-6-(8-methoxy-6,11,11-trioxobenzo[b][1,4]benzothiazepin-5-yl)hexanamide	IC50	0.8 nM	US-10188756: Imaging histone deacetylases with a radiotracer using positron emission tomography
N-(2-amino-5-thiophen-2-ylphenyl)-4-[[1-(morpholine-4-carbonyl)piperidin-4-yl]amino]benzamide	IC50	0.9 nM	US-9790180: Piperidine derivatives as HDAC1/2 inhibitors
(E)-3-[4-[(1-adamantylmethylamino)methyl]phenyl]-N-hydroxyprop-2-enamide	IC50	0.95 nM	US-10188756: Imaging histone deacetylases with a radiotracer using positron emission tomography
Panobinostat	IC50	1 nM
N-hydroxy-6-(8-methoxy-6-oxobenzo[b][1,4]benzothiazepin-5-yl)hexanamide	IC50	1.2 nM	US-10188756: Imaging histone deacetylases with a radiotracer using positron emission tomography
N-(2-amino-5-thiophen-2-ylphenyl)-4-[[1-(4-methylpiperazine-1-carbonyl)piperidin-4-yl]amino]benzamide	IC50	1.2 nM	US-9790180: Piperidine derivatives as HDAC1/2 inhibitors
(E)-3-[4-[(cyclohexylmethylamino)methyl]-3-fluorophenyl]-N-hydroxyprop-2-enamide	IC50	1.64 nM	US-10188756: Imaging histone deacetylases with a radiotracer using positron emission tomography
(E)-3-[4-[(cyclohexylmethylamino)methyl]phenyl]-N-hydroxyprop-2-enamide	IC50	1.8 nM	US-10188756: Imaging histone deacetylases with a radiotracer using positron emission tomography
BRD2492	IC50	2 nM
N-(2-amino-5-thiophen-2-ylphenyl)-4-[[4-methyl-1-(morpholine-4-carbonyl)piperidin-4-yl]amino]benzamide	IC50	2 nM	US-9790180: Piperidine derivatives as HDAC1/2 inhibitors
NVP-LAQ824	IC50	2.6 nM
N-hydroxy-2-[[1-[2-(1H-indol-3-yl)acetyl]-4-phenylpiperidin-4-yl]amino]pyrimidine-5-carboxamide	IC50	3 nM	US-9278963: Pyrimidine hydroxy amide compounds as histone deacetylase inhibitors
N-(2-amino-5-thiophen-2-ylphenyl)-8-cyclopropyl-7-piperazin-1-ylquinoline-3-carboxamide	IC50	3.1 nM	US-9145412: Selective HDAC1 and HDAC2 inhibitors
N-(2-amino-5-thiophen-2-ylphenyl)-4-[[4-methyl-1-(piperazine-1-carbonyl)piperidin-4-yl]amino]benzamide	IC50	3.2 nM	US-9790180: Piperidine derivatives as HDAC1/2 inhibitors
N-(2-amino-5-thiophen-2-ylphenyl)-4-[[4-methyl-1-(4-methylpiperazine-1-carbonyl)piperidin-4-yl]amino]benzamide	IC50	3.2 nM	US-9790180: Piperidine derivatives as HDAC1/2 inhibitors
N-(2-amino-5-thiophen-2-ylphenyl)-4-[[4-ethyl-1-(piperazine-1-carbonyl)piperidin-4-yl]amino]benzamide	IC50	3.9 nM	US-9790180: Piperidine derivatives as HDAC1/2 inhibitors
N-(2-amino-5-thiophen-2-ylphenyl)-2-piperazin-1-ylquinoline-6-carboxamide	IC50	4 nM	US-9145412: Selective HDAC1 and HDAC2 inhibitors
N-[2-amino-5-(thiophen-2-yl)phenyl]-4-{1,8-diazaspiro[4.5]decan-8-ylmethyl}benzamide	IC50	4 nM
N-(2-amino-5-thiophen-2-ylphenyl)-4-[[4-methyl-1-(pyrrolidine-1-carbonyl)piperidin-4-yl]amino]benzamide	IC50	4 nM	US-9790180: Piperidine derivatives as HDAC1/2 inhibitors
N-(2-amino-5-thiophen-2-ylphenyl)-4-[[1-(pyrrolidine-1-carbonyl)piperidin-4-yl]amino]benzamide	IC50	4.7 nM	US-9790180: Piperidine derivatives as HDAC1/2 inhibitors
(E)-3-[2-butyl-1-[2-(dimethylamino)ethyl]benzimidazol-5-yl]-N-hydroxyprop-2-enamide	IC50	4.7 nM	US-10188756: Imaging histone deacetylases with a radiotracer using positron emission tomography
CHEBI:46024	IC50	4.9 nM
2-[[1-(2,6-difluorophenyl)cyclopropyl]amino]-N-hydroxypyrimidine-5-carboxamide	IC50	5 nM	US-8614223: Pyrimidine hydroxy amide compounds as protein deacetylase inhibitors and methods of use thereof
(E)-N-hydroxy-3-[3-[methyl(2-phenylethyl)sulfamoyl]phenyl]prop-2-enamide	IC50	5 nM	US-10188756: Imaging histone deacetylases with a radiotracer using positron emission tomography
N-(2-amino-5-thiophen-2-ylphenyl)-4-[[1-(oxane-4-carbonyl)piperidin-4-yl]amino]benzamide	IC50	5 nM	US-9790180: Piperidine derivatives as HDAC1/2 inhibitors
(E)-3-[4-[[cyclohexylmethyl(methyl)amino]methyl]-3-fluorophenyl]-N-hydroxyprop-2-enamide	IC50	5.43 nM	US-10188756: Imaging histone deacetylases with a radiotracer using positron emission tomography
R-TSA	IC50	5.76 nM
N-hydroxy-2-[[4-phenyl-1-(phenylcarbamothioyl)piperidin-4-yl]amino]pyrimidine-5-carboxamide	IC50	5.9 nM	US-9278963: Pyrimidine hydroxy amide compounds as histone deacetylase inhibitors
N-(2-amino-5-thiophen-2-ylphenyl)-2-cyclopropyl-1-(2-morpholin-4-ylethyl)pyrrolo[2,3-b]pyridine-5-carboxamide	IC50	6 nM	US-9145412: Selective HDAC1 and HDAC2 inhibitors
2-N-hydroxy-5-N-[(1R)-1-phenylethyl]thiophene-2,5-dicarboxamide	IC50	6 nM
N-(2-amino-5-thiophen-2-ylphenyl)-4-[[1-(1-hydroxycyclohexanecarbonyl)piperidin-4-yl]amino]benzamide	IC50	6 nM	US-9790180: Piperidine derivatives as HDAC1/2 inhibitors
N-[7-(hydroxyamino)-7-oxoheptyl]-4-(methylamino)benzamide	IC50	6.1 nM	US-10188756: Imaging histone deacetylases with a radiotracer using positron emission tomography
N-(2-amino-5-thiophen-2-ylphenyl)-2-[[4-methyl-1-(propan-2-ylcarbamoyl)piperidin-4-yl]amino]pyrimidine-5-carboxamide	IC50	6.5 nM	US-9790180: Piperidine derivatives as HDAC1/2 inhibitors
N-(2-amino-5-phenylphenyl)-1-(2-morpholin-4-ylethyl)pyrrolo[2,3-b]pyridine-5-carboxamide	IC50	6.8 nM	US-9145412: Selective HDAC1 and HDAC2 inhibitors
2-[[1-[2-fluoro-5-(trifluoromethyl)phenyl]cyclopropyl]amino]-N-hydroxypyrimidine-5-carboxamide	IC50	7 nM	US-8614223: Pyrimidine hydroxy amide compounds as protein deacetylase inhibitors and methods of use thereof
N-(2-amino-5-thiophen-2-ylphenyl)-2-piperazin-1-ylquinoxaline-6-carboxamide	IC50	7 nM	US-9145412: Selective HDAC1 and HDAC2 inhibitors
3-[(dimethylamino)methyl]-N-{2-[4-(hydroxycarbamoyl)phenoxy]ethyl}-1-benzofuran-2-carboxamide	KI	7 nM
N-(2-amino-5-thiophen-2-ylphenyl)-2-[[1-(4-methylpiperazine-1-carbonyl)-4-propan-2-ylpiperidin-4-yl]amino]pyrimidine-5-carboxamide	IC50	7 nM	US-9790180: Piperidine derivatives as HDAC1/2 inhibitors
N-(2-amino-5-thiophen-2-ylphenyl)-4-[[1-(1-hydroxycyclopentanecarbonyl)piperidin-4-yl]amino]benzamide	IC50	7 nM	US-9790180: Piperidine derivatives as HDAC1/2 inhibitors
N-(2-amino-5-phenylphenyl)-1-[2-(4-methylpiperazin-1-yl)ethyl]indazole-5-carboxamide	IC50	7.1 nM	US-9145412: Selective HDAC1 and HDAC2 inhibitors
N-(2-amino-5-pyridin-4-ylphenyl)-4-[[4-methyl-1-(pyrrolidine-1-carbonyl)piperidin-4-yl]amino]benzamide	IC50	7.1 nM	US-9790180: Piperidine derivatives as HDAC1/2 inhibitors
N-(2-amino-5-thiophen-2-ylphenyl)-2-[[4-methyl-1-(piperazine-1-carbonyl)piperidin-4-yl]amino]pyrimidine-5-carboxamide	IC50	7.3 nM	US-9790180: Piperidine derivatives as HDAC1/2 inhibitors
4-(dimethylamino)-N-(7-(hydroxyamino)-7-oxoheptyl)benzamide	IC50	7.3 nM	US-10188756: Imaging histone deacetylases with a radiotracer using positron emission tomography
N-(2-amino-5-phenylphenyl)-1-(2-morpholin-4-ylethyl)indazole-5-carboxamide	IC50	7.4 nM	US-9145412: Selective HDAC1 and HDAC2 inhibitors
N-(2-amino-5-phenylphenyl)-8-cyclopropyl-7-piperazin-1-ylquinoline-3-carboxamide	IC50	7.8 nM	US-9145412: Selective HDAC1 and HDAC2 inhibitors
HDAC inhibitor, Compound 2	IC50	7.93 nM

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

2874 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	decreases activity, decreases expression, affects binding, affects cotreatment, decreases reaction (+2 more)	6
sodium arsenite	increases expression, decreases expression, decreases reaction	3
Vorinostat	affects binding, decreases expression, decreases activity	3
bisphenol A	affects expression, decreases expression	2
manganese chloride	affects binding, increases abundance, increases reaction, increases expression, decreases reaction	2
Air Pollutants	affects expression, increases abundance, decreases expression	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	affects binding, decreases phosphorylation, decreases expression, decreases reaction, increases reaction (+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)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT00517959	PHASE3	UNKNOWN	SCRT Versus Conventional RT in Children and Young Adults With Low Grade and Benign Brain Tumors
NCT01096368	PHASE3	COMPLETED	Maintenance Chemotherapy or Observation Following Induction Chemotherapy and Radiation Therapy in Treating Patients With Newly Diagnosed Ependymoma
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00003479	PHASE2	TERMINATED	Antineoplaston Therapy in Treating Patients With Ependymoma
NCT00520936	PHASE2	COMPLETED	A Study of Pemetrexed in Children With Recurrent Cancer
NCT00840047	PHASE2	ACTIVE_NOT_RECRUITING	Methionine PET/CT Studies In Patients With Cancer
NCT01088035	PHASE2	TERMINATED	Carboplatin as a Radiosensitizer in Treating Childhood Ependymoma
NCT01247922	PHASE2	TERMINATED	Single-agent Erlotinib in Patients Previously Treated With Oral Etoposide in Protocol OSI-774-205
NCT01288235	PHASE2	COMPLETED	Proton Radiotherapy for Pediatric Brain Tumors Requiring Partial Brain Irradiation
NCT01295944	PHASE2	COMPLETED	Carboplatin and Bevacizumab for Recurrent Ependymoma
NCT01356290	PHASE2	RECRUITING	Antiangiogenic Therapy for Children With Recurrent Medulloblastoma, Ependymoma, ATRT and Rare CNS Tumors
NCT01836549	PHASE2	TERMINATED	Imetelstat Sodium in Treating Younger Patients With Recurrent or Refractory Brain Tumors
NCT02125786	PHASE2	ACTIVE_NOT_RECRUITING	A Trial of Surgery and Fractionated Re-Irradiation for Recurrent Ependymoma
NCT02689336	PHASE2	WITHDRAWN	Erlotinib in Combination With Temozolomide in Treating Relapsed/Recurrent/Refractory Pediatric Solid Tumors
NCT03095248	PHASE2	TERMINATED	Trial of Selumetinib in Patients With Neurofibromatosis Type II Related Tumors
NCT03155620	PHASE2	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	PHASE2	COMPLETED	Immune Checkpoint Inhibitor Nivolumab in People With Recurrent Select Rare CNS Cancers
NCT03194906	PHASE2	COMPLETED	Memantine for Prevention of Cognitive Late Effects in Pediatric Patients Receiving Cranial Radiation Therapy for Localized Brain Tumors
NCT03210714	PHASE2	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	PHASE2	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	PHASE2	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	PHASE2	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	PHASE2	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	PHASE2	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	PHASE2	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	PHASE2	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	PHASE2	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	PHASE2	TERMINATED	Marizomib for Recurrent Low-Grade and Anaplastic Supratentorial, Infratentorial, and Spinal Cord Ependymoma
NCT04049669	PHASE2	ACTIVE_NOT_RECRUITING	Pediatric Trial of Indoximod With Chemotherapy and Radiation for Relapsed Brain Tumors or Newly Diagnosed DIPG
NCT04195555	PHASE2	ACTIVE_NOT_RECRUITING	Ivosidenib in Treating Patients With Advanced Solid Tumors, Lymphoma, or Histiocytic Disorders With IDH1 Mutations (A Pediatric MATCH Treatment Trial)
NCT04284774	PHASE2	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	PHASE2	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