HDAC9

Summary

HDAC9 (histone deacetylase 9, HGNC:14065) is a protein-coding gene on chromosome 7p21.1, encoding Histone deacetylase 9 (Q9UKV0). Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4).

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 has sequence homology to members of the histone deacetylase family. This gene is orthologous to the Xenopus and mouse MITR genes. The MITR protein lacks the histone deacetylase catalytic domain. It represses MEF2 activity through recruitment of multicomponent corepressor complexes that include CtBP and HDACs. This encoded protein may play a role in hematopoiesis. Multiple alternatively spliced transcripts have been described for this gene but the full-length nature of some of them has not been determined.

Source: NCBI Gene 9734 — RefSeq curated summary.

At a glance

• Gene–disease (curated): auriculocondylar syndrome 4 (Limited, GenCC) — +1 more curated relationship
• GWAS associations: 87
• Clinical variants (ClinVar): 162 total — 2 pathogenic, 1 likely-pathogenic
• Phenotypes (HPO): 13
• Druggable target: yes — 28 molecules with ChEMBL bioactivity
• Transcription factor: yes — 19 downstream targets (CollecTRI)
• MANE Select transcript: NM_178425

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14065
Approved symbol	HDAC9
Name	histone deacetylase 9
Location	7p21.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0744, HDAC, MITR, HD7, HDAC7B
Ensembl gene	ENSG00000048052
Ensembl biotype	protein_coding
OMIM	606543
Entrez	9734

Gene structure

Transcript identifiers

Ensembl transcripts: 42 — 29 protein_coding, 8 protein_coding_CDS_not_defined, 4 retained_intron, 1 nonsense_mediated_decay

ENST00000401921, ENST00000405010, ENST00000406072, ENST00000406451, ENST00000411993, ENST00000413380, ENST00000413509, ENST00000417496, ENST00000425071, ENST00000428307, ENST00000430454, ENST00000432645, ENST00000433709, ENST00000441542, ENST00000441986, ENST00000446646, ENST00000455069, ENST00000456174, ENST00000461159, ENST00000461409, ENST00000471887, ENST00000474742, ENST00000476135, ENST00000483142, ENST00000490851, ENST00000496026, ENST00000523867, ENST00000524023, ENST00000622668, ENST00000681273, ENST00000681950, ENST00000686413, ENST00000707077, ENST00000707080, ENST00000707081, ENST00000707082, ENST00000868968, ENST00000868969, ENST00000868970, ENST00000868971, ENST00000868972, ENST00000935502

RefSeq mRNA: 39 — MANE Select: NM_178425 NM_001204144, NM_001204145, NM_001204146, NM_001204147, NM_001204148, NM_001321868, NM_001321869, NM_001321870, NM_001321871, NM_001321872, NM_001321873, NM_001321874, NM_001321875, NM_001321876, NM_001321877, NM_001321878, NM_001321879, NM_001321884, NM_001321885, NM_001321886, NM_001321887, NM_001321888, NM_001321889, NM_001321890, NM_001321891, NM_001321893, NM_001321894, NM_001321895, NM_001321896, NM_001321897, NM_001321898, NM_001321899, NM_001321900, NM_001321901, NM_001321902, NM_014707, NM_058176, NM_178423, NM_178425

CCDS: CCDS47553, CCDS47554, CCDS47555, CCDS47557, CCDS56465, CCDS56466, CCDS56467, CCDS56468, CCDS75565, CCDS83163, CCDS94058, CCDS94059

Canonical transcript exons

ENST00000686413 — 26 exons

Exon	Start	End
ENSE00002620825	18996023	19002416
ENSE00003469169	18634627	18634742
ENSE00003470295	18835467	18835586
ENSE00003494307	18591516	18591642
ENSE00003494780	18829461	18829548
ENSE00003496922	18874478	18874596
ENSE00003497085	18767106	18767155
ENSE00003516851	18666213	18666476
ENSE00003517875	18749005	18749138
ENSE00003524474	18496262	18496324
ENSE00003533224	18793345	18793452
ENSE00003573192	18935809	18935942
ENSE00003591924	18629350	18629481
ENSE00003597797	18727580	18727757
ENSE00003608932	18647785	18647998
ENSE00003618602	18954146	18954230
ENSE00003639067	18593908	18594029
ENSE00003643746	18585281	18585522
ENSE00003644906	18762157	18762277
ENSE00003662548	18975806	18975953
ENSE00003665477	18648466	18648683
ENSE00003667557	18829161	18829216
ENSE00003668270	18835900	18835997
ENSE00003680086	18644671	18644793
ENSE00003790684	18590336	18590486
ENSE00003936346	18495749	18496023

Expression profiles

Bgee: expression breadth ubiquitous, 277 present calls, max score 94.38.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 23.6630 / max 1106.6858, expressed in 1483 samples.

FANTOM5 promoters (33 alternative TSS)

Promoter ID	TPM avg	Samples expressed
77384	5.9103	818
77397	5.0656	813
77394	2.9617	801
77375	2.9222	352
77396	1.4204	588
77368	1.0529	274
77383	0.7748	341
77391	0.6106	247
77366	0.3461	159
77389	0.3410	151

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
oocyte	CL:0000023	94.38	gold quality
monocyte	CL:0000576	94.21	gold quality
secondary oocyte	CL:0000655	93.93	gold quality
mononuclear cell	CL:0000842	93.76	gold quality
leukocyte	CL:0000738	92.93	gold quality
endothelial cell	CL:0000115	92.12	gold quality
choroid plexus epithelium	UBERON:0003911	91.62	gold quality
parotid gland	UBERON:0001831	90.81	gold quality
ganglionic eminence	UBERON:0004023	90.74	gold quality
cortical plate	UBERON:0005343	90.53	gold quality
skeletal muscle tissue of rectus abdominis	UBERON:0004511	90.28	gold quality
ventricular zone	UBERON:0003053	90.01	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	89.68	gold quality
epithelium of nasopharynx	UBERON:0001951	89.00	gold quality
corpus callosum	UBERON:0002336	88.78	gold quality
superficial temporal artery	UBERON:0001614	88.23	gold quality
calcaneal tendon	UBERON:0003701	88.23	gold quality
bone marrow cell	CL:0002092	87.44	gold quality
islet of Langerhans	UBERON:0000006	87.07	gold quality
Brodmann (1909) area 46	UBERON:0006483	87.07	gold quality
colonic epithelium	UBERON:0000397	86.83	gold quality
Brodmann (1909) area 23	UBERON:0013554	86.61	gold quality
lymph node	UBERON:0000029	86.58	gold quality
orbitofrontal cortex	UBERON:0004167	86.49	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.04	gold quality
middle temporal gyrus	UBERON:0002771	85.98	gold quality
mucosa of stomach	UBERON:0001199	85.97	gold quality
lower esophagus muscularis layer	UBERON:0035833	85.39	gold quality
left testis	UBERON:0004533	85.30	gold quality
lower esophagus	UBERON:0013473	85.29	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-HCAD-35	yes	27.49
E-MTAB-9801	yes	7.66
E-ANND-3	yes	6.60

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

19 targets.

Target	Regulation
APP	Unknown
CDKN2A	Activation
CFLAR	Activation
CITED2	Repression
DIRAS3	Repression
ESR1	Repression
HSPA5	Repression
IGFBP1	Repression
IL18	Unknown
LPL	Repression
MEF2A	Repression
MMP13	Activation
MYEF2	Repression
NFKB1	Repression
PRL	Repression
RELA	Repression
STAT6	Repression
TNFRSF10B	Repression
TP53	Repression

Upstream regulators (CollecTRI, top): GATA4, NR4A1, SALL3

miRNA regulators (miRDB)

161 targeting HDAC9, 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-1252-5P	100.00	69.80	2774
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-30A-5P	100.00	76.31	3233
HSA-MIR-30B-5P	100.00	76.29	3248
HSA-MIR-30C-5P	100.00	76.29	3248
HSA-MIR-30D-5P	100.00	76.32	3233
HSA-MIR-30E-5P	100.00	76.32	3242
HSA-MIR-3924	100.00	72.09	2394
HSA-LET-7A-3P	100.00	74.03	3932
HSA-LET-7B-3P	100.00	74.08	3913
HSA-LET-7F-1-3P	100.00	74.02	3928
HSA-MIR-98-3P	100.00	74.08	3907
HSA-MIR-3646	100.00	73.56	5283
HSA-MIR-6758-5P	100.00	66.21	1470
HSA-MIR-190A-3P	100.00	80.35	5520
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-656-3P	100.00	72.15	2788
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-7110-3P	100.00	73.18	2486
HSA-MIR-3662	99.99	73.82	5684
HSA-MIR-6077	99.99	68.04	2299
HSA-MIR-548AW	99.99	72.57	3559
HSA-MIR-371B-5P	99.99	75.34	4759
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-616-5P	99.98	75.58	4775
HSA-MIR-373-5P	99.98	75.36	4753
HSA-MIR-3692-3P	99.98	70.27	2139
HSA-MIR-4775	99.98	75.00	6394

Literature-anchored findings (GeneRIF, showing 40)

• Chromosomal organization on chromsome 7 (PMID:12054582)
• ICP0 of Herpes simplex virus Type 1 interacts with and controls the repressor activity of class II HDAC7 (PMID:15194749)
• The crystal structure of a histone deacetylase 9 (HDAC9)/myocyte enhancer factor-2 (MEF2)/DNA complex reveals that HDAC9 binds to a hydrophobic groove of the MEF2 dimer. (PMID:15567413)
• Moraxella catarrhalis-induced cytokine expression is regulated by acetylation of histone residues and controlled by histone deacetylase activity. (PMID:16399788)
• The role of ACTN4 in MEF2A transcription via HDAC7 antagonism is reported. (PMID:16980305)
• FOXP3 interactions with histone acetyltransferase and class II histone deacetylases are required for repression (PMID:17360565)
• Endogenous HDAC activity plays a crucial role in maintaining the balance of pre-established T(H)1-like and T(H)2-like responses, inhibiting excessive T(H)2 immunity. (PMID:17980413)
• amino enhancer of split has apoptotic activity in neurons and suggest that neuroprotection by histone deacetylase-related protein is mediated by the inhibition of this activity through direct interaction. (PMID:18438919)
• Analysis of chromatin modification patterns shows that HDAC are recruited to the c-myc promoter leading to appearance of repressive chromatin marks. (PMID:19522008)
• HDAC suppresses the activation of PPARgamma in the gastric carcinoma cell line SGC-7901. (PMID:19624894)
• Results demonstrate that histone deacetylase inhibitors (HDACIs) in different combinations with RA, act as cell growth inhibitors. (PMID:19723072)
• Histone deacetylase 9 (HDAC9) regulates the functions of the ATDC (TRIM29) protein (PMID:20947501)
• enforced HDAC9 expression increased gamma-globin mRNA levels by 2.5-fold with a simultaneous 7-fold increase in HbF. (PMID:21078662)
• Histone deacetylases 9 and 10 are required for homologous recombination. (PMID:21247901)
• MITR plays a master switch role to balance osteogenic and adipogenic differentiation of MSCs through regulation of PPARgamma-2 transcriptional activity. (PMID:21247904)
• HDAC9 acts as an epigenetic switch in effector T cell-mediated systemic autoimmunity. (PMID:21708950)
• Data indicate a pronounced deregulation of HDAC genes HDAC9 and HDAC11 in patients with Philadelphia-negative chronic myeloproliferative neoplasms: essential thrombocythemia (ET), polycythemia vera (PV) and primary myelofibrosis (PMF). (PMID:21806350)
• Treated the seminoma-like cell line TCam-2 with the HDAC-inhibitor Depsipeptide. (PMID:21987446)
• The results show that hdac9 is the third androgenic alopecia susceptibility gene (PMID:22032556)
• The results imply that HDAC9 is involved in the transcriptional regulation of human odontoblasts in vivo. (PMID:22297573)
• We identified a new association for large vessel stroke within HDAC9 on chromosome 7p21.1. (PMID:22306652)
• LBH589 and TSA may translationally regulate some HDAC encoding genes in pancreatic tumors. (PMID:22487525)
• Regression models consistently identified rs2522129, rs2675231, and rs2389963 as having among the highest predictive values for explaining differences related to brain volume measures (PMID:22884548)
• We propose that CtBP2 is an ovarian cancer oncogene that regulates gene expression program by modulating HDAC activity. (PMID:22945647)
• HDAC9 promotes angiogenesis and transcriptionally represses the endothelial cell miR-17-92 cluster. (PMID:23288173)
• Dephosphorylation at a conserved SP motif governs cAMP sensitivity and nuclear localization of class IIa histone deacetylases HDAC4, 5 and 9 (PMID:23297420)
• SNP, rs12155400, in the histone deacetylase 9 gene (HDAC9) on chromosome 7, was associated with retinopathy in analysis of participants without hypertension (PMID:23393555)
• Our results are consistent with the 7p21.1 association acting via promoting atherosclerosis, and consistent with alterations in HDAC9 expression mediating this increased risk. (PMID:23449258)
• In vivo sorafenib + HDAC inhibitor toxicity against tumors was increased. (PMID:23674352)
• study reports gene expression in skeletal muscle tissue of women with metabolic syndrome is enriched in inflammatory response-related genes; IL6R, HDAC9 and CD97 expression correlated negatively with insulin sensitivity; suggests a role for these 3 inflammatory genes in development of skeletal muscle insulin resistance in women (PMID:23771909)
• These data suggest that HDAC9 variants may be selected for during cutaneous squamous cell carcinoma tumorigenesis (PMID:23784969)
• HDAC9 gene is significantly associated with large-vessel stroke risk in Chinese population. (PMID:23828597)
• These results suggest that HDAC9 may be a suppressor and its downregulation might promote the progression process, especially in lung adenocarcinomas. (PMID:24427341)
• The hydroxamic acid pan-HDAC inhibitor TSA synergistically inhibit the viability. (PMID:24562770)
• The results elucidate the genetic etiology of lung adenocarcinoma by demonstrating that SNP rs10248565 in the HDAC9 gene may be a potential biomarker of cancer susceptibility. (PMID:24650256)
• Gene expression studies in peripheral blood mononuclear cells revealed increased mRNA levels of HDAC9. Analysis of human atherosclerotic plaques revealed no association between rs2107595 and specific plaque characteristics. (PMID:25388417)
• Data show that miR-376a and HDAC9 expression are inversely correlated in hepatocellular carcinoma and suggest that HDAC9-mediated epigenetic modification may contribute to the down-regulation of the miR-376 cluster in hepatocellular carcinoma. (PMID:25613642)
• HDAC9 promotes tumor formation of glioblastoma via TAZ-mediated EGFR pathway activation. (PMID:25760078)
• the results of this study suggest that targeting HDACs by ST-3595 might represent as a novel and promising anti-pancreatic cancer strategy. (PMID:26084607)
• results indicate that HDAC9 variant rs2107595 may be not associated with IS risk in southern Han Chinese (PMID:26093197)

Cross-species orthologs

8 orthologs

Organism	Symbol	Gene ID
danio_rerio	hdac9b	ENSDARG00000056642
mus_musculus	Hdac9	ENSMUSG00000004698
rattus_norvegicus	Hdac9	ENSRNOG00000004158
drosophila_melanogaster	HDAC4	FBGN0041210
caenorhabditis_elegans		WBGENE00001837
caenorhabditis_elegans		WBGENE00009657
caenorhabditis_elegans		WBGENE00009663
caenorhabditis_elegans		WBGENE00219378

Paralogs (10): HDAC7 (ENSG00000061273), HDAC4 (ENSG00000068024), HDAC6 (ENSG00000094631), HDAC10 (ENSG00000100429), HDAC5 (ENSG00000108840), HDAC1 (ENSG00000116478), HDAC8 (ENSG00000147099), HDAC11 (ENSG00000163517), HDAC3 (ENSG00000171720), HDAC2 (ENSG00000196591)

Protein

Protein identifiers

Histone deacetylase 9 — Q9UKV0 (reviewed: Q9UKV0)

Alternative names: Histone deacetylase 7B, Histone deacetylase-related protein, MEF2-interacting transcription repressor MITR

All UniProt accessions (15): A0A7P0T8F4, A0A7P0TAB5, A0A9L9PXL9, Q9UKV0, A0A9L9PXM4, A0A9L9PY57, A0A9L9PY89, B5MCF1, B7Z3P7, C9IZS0, C9J1W4, C9J835, C9JD56, C9JLX1, F8WDS2

UniProt curated annotations — full annotation on UniProt →

Function. Responsible for the deacetylation of lysine residues on the N-terminal part of the core histones (H2A, H2B, H3 and H4). Histone deacetylation gives a tag for epigenetic repression and plays an important role in transcriptional regulation, cell cycle progression and developmental events. Represses MEF2-dependent transcription. Isoform 3 lacks active site residues and therefore is catalytically inactive. Represses MEF2-dependent transcription by recruiting HDAC1 and/or HDAC3. Seems to inhibit skeletal myogenesis and to be involved in heart development. Protects neurons from apoptosis, both by inhibiting JUN phosphorylation by MAPK10 and by repressing JUN transcription via HDAC1 recruitment to JUN promoter.

Subunit / interactions. Homodimer. Interacts with CTBP1. The phosphorylated form interacts with 14-3-3. Interacts with HDAC1 and HDAC3, and probably with HDAC4 and HDAC5. Interacts with MEF2, MAPK10, ETV6, NCOR1 and BCL6. Interacts with FOXP3 in the absence of T-cell stimulation.

Subcellular location. Nucleus.

Tissue specificity. Broadly expressed, with highest levels in brain, heart, muscle and testis. Isoform 3 is present in human bladder carcinoma cells (at protein level).

Post-translational modifications. Phosphorylated on Ser-220 and Ser-450; which promotes 14-3-3-binding, impairs interaction with MEF2, and antagonizes antimyogenic activity. Phosphorylated on Ser-240; which impairs nuclear accumulation. Isoform 7 is phosphorylated on Tyr-1010. Phosphorylated by the PKC kinases PKN1 and PKN2, impairing nuclear import. Sumoylated.

Disease relevance. Auriculocondylar syndrome 4 (ARCND4) [MIM:620457] An autosomal dominant form of auriculocondylar syndrome, a craniofacial malformation syndrome characterized by variable mandibular anomalies, including mild to severe micrognathia, temporomandibular joint ankylosis, cleft palate, and a characteristic ear malformation that consists of separation of the lobule from the external ear, giving the appearance of a question mark (question-mark ear). Other frequently described features include prominent cheeks, cupped and posteriorly rotated ears, preauricular tags, and microstomia. Glossoptosis, masticatory abnormalities, orthodontic problems, and malocclusion occur in a majority of affected subjects. The disease may be caused by variants affecting the gene represented in this entry. A chromosomal aberration involving HDAC9 is found in a family with Peters anomaly. Translocation t(1;7)(q41;p21) with TGFB2 resulting in lack of HDAC9 protein.

Activity regulation. Inhibited by Trichostatin A (TSA) and suberoylanilide hydroxamic acid.

Miscellaneous. Major form in most tissues. Inactive due to lack of active site residues. Excluded from the nucleus. Does not interact with ETV6.

Similarity. Belongs to the histone deacetylase family. HD type 2 subfamily.

Isoforms (11)

UniProt ID	Names	Canonical?
Q9UKV0-1	1	yes
Q9UKV0-2	2
Q9UKV0-3	3, HDRP, MITR
Q9UKV0-4	4, HDAC9a
Q9UKV0-5	5, HDAC9b, HDAC9fl
Q9UKV0-6	6
Q9UKV0-7	7
Q9UKV0-8	8
Q9UKV0-9	9
Q9UKV0-10	10
Q9UKV0-11	11

RefSeq proteins (39): NP_001191073, NP_001191074, NP_001191075, NP_001191076, NP_001191077, NP_001308797, NP_001308798, NP_001308799, NP_001308800, NP_001308801, NP_001308802, NP_001308803, NP_001308804, NP_001308805, NP_001308806, NP_001308807, NP_001308808, NP_001308813, NP_001308814, NP_001308815, NP_001308816, NP_001308817, NP_001308818, NP_001308819, NP_001308820, NP_001308822, NP_001308823, NP_001308824, NP_001308825, NP_001308826, NP_001308827, NP_001308828, NP_001308829, NP_001308830, NP_001308831, NP_055522, NP_478056, NP_848510, NP_848512* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000286	HDACs	Family
IPR023696	Ureohydrolase_dom_sf	Homologous_superfamily
IPR023801	His_deacetylse_dom	Domain
IPR024643	Hist_deacetylase_Gln_rich_N	Domain
IPR037138	His_deacetylse_dom_sf	Homologous_superfamily
IPR046949	HDAC4/5/7/9	Family

Pfam: PF00850, PF12203

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), 1 shown:

• N(6)-acetyl-L-lysyl-[histone] + H2O = L-lysyl-[histone] + acetate (RHEA:58196)

UniProt features (47 total): splice variant 11, region of interest 9, sequence conflict 9, compositionally biased region 5, modified residue 5, binding site 4, chain 1, active site 1, sequence variant 1, helix 1

Structure

Experimental structures (PDB)

2 structures.

PDB	Method	Resolution (Å)
8Q9N	X-RAY DIFFRACTION	1.51
8Q9R	X-RAY DIFFRACTION	2.25

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9UKV0-F1	64.48	0.33

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): 783

Ligand- & substrate-binding residues (4): 646; 648; 654; 731

Post-translational modifications (5): 22, 220, 240, 451, 554

Function

Pathways and Gene Ontology

Reactome pathways

5 pathways

ID	Pathway
R-HSA-2122947	NOTCH1 Intracellular Domain Regulates Transcription
R-HSA-2644606	Constitutive Signaling by NOTCH1 PEST Domain Mutants
R-HSA-2894862	Constitutive Signaling by NOTCH1 HD+PEST Domain Mutants
R-HSA-350054	Notch-HLH transcription pathway
R-HSA-9976102	Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)

MSigDB gene sets: 516 (showing top): GSE45365_NK_CELL_VS_CD8_TCELL_UP, PID_HDAC_CLASSI_PATHWAY, REACTOME_SIGNALING_BY_NOTCH, GOBP_RESPONSE_TO_NITROGEN_COMPOUND, RODRIGUES_THYROID_CARCINOMA_ANAPLASTIC_UP, BROWNE_HCMV_INFECTION_6HR_DN, GOBP_MUSCLE_TISSUE_DEVELOPMENT, WWTAAGGC_UNKNOWN, HARRIS_HYPOXIA, GOBP_INFLAMMATORY_RESPONSE, GOBP_STEROL_HOMEOSTASIS, RORA1_01, GOBP_B_CELL_ACTIVATION, NKX25_02, GCANCTGNY_MYOD_Q6

GO Biological Process (16): negative regulation of transcription by RNA polymerase II (GO:0000122), negative regulation of cytokine production (GO:0001818), inflammatory response (GO:0006954), heart development (GO:0007507), B cell differentiation (GO:0030183), cellular response to insulin stimulus (GO:0032869), epigenetic regulation of gene expression (GO:0040029), B cell activation (GO:0042113), cholesterol homeostasis (GO:0042632), negative regulation of gene expression, epigenetic (GO:0045814), negative regulation of DNA-templated transcription (GO:0045892), regulation of skeletal muscle fiber development (GO:0048742), regulation of striated muscle cell differentiation (GO:0051153), positive regulation of cell migration involved in sprouting angiogenesis (GO:0090050), chromatin organization (GO:0006325), negative regulation of macromolecule biosynthetic process (GO:0010558)

GO Molecular Function (14): transcription corepressor activity (GO:0003714), histone deacetylase activity (GO:0004407), protein kinase C binding (GO:0005080), histone H3K14 deacetylase activity, hydrolytic mechanism (GO:0031078), histone H3K9 deacetylase activity, hydrolytic mechanism (GO:0032129), protein lysine deacetylase activity (GO:0033558), histone H4K16 deacetylase activity, hydrolytic mechanism (GO:0034739), histone deacetylase binding (GO:0042826), metal ion binding (GO:0046872), RNA polymerase II-specific DNA-binding transcription factor binding (GO:0061629), DNA-binding transcription factor binding (GO:0140297), protein binding (GO:0005515), hydrolase activity (GO:0016787), histone deacetylase activity, hydrolytic mechanism (GO:0141221)

GO Cellular Component (6): histone deacetylase complex (GO:0000118), nucleus (GO:0005634), nucleoplasm (GO:0005654), transcription regulator complex (GO:0005667), cytoplasm (GO:0005737), histone methyltransferase complex (GO:0035097)

Reactome top-level categories

Rollup of top-5 pathways:

Category	Pathways
Signaling by NOTCH1	1
Signaling by NOTCH1 PEST Domain Mutants in Cancer	1
Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer	1
Generic Transcription Pathway	1
Differentiation of T cells	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
histone deacetylase activity, hydrolytic mechanism	3
negative regulation of DNA-templated transcription	2
negative regulation of gene expression	2
histone H3K deacetylase activity	2
nucleoplasm	2
nuclear protein-containing complex	2
cellular anatomical structure	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
cytokine production	1
regulation of cytokine production	1
negative regulation of multicellular organismal process	1
defense response	1
animal organ development	1
circulatory system development	1
lymphocyte differentiation	1
B cell activation	1
response to insulin	1
cellular response to peptide hormone stimulus	1
chromatin remodeling	1
regulation of gene expression	1
lymphocyte activation	1
sterol homeostasis	1
epigenetic regulation of gene expression	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
regulation of myotube differentiation	1
skeletal muscle fiber development	1
regulation of cell development	1
striated muscle cell differentiation	1
regulation of muscle cell differentiation	1
cell migration involved in sprouting angiogenesis	1
positive regulation of blood vessel endothelial cell migration	1
regulation of cell migration involved in sprouting angiogenesis	1
cellular component organization	1
macromolecule biosynthetic process	1
negative regulation of biosynthetic process	1
regulation of macromolecule biosynthetic process	1
negative regulation of macromolecule metabolic process	1

Protein interactions and networks

STRING

2922 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
HDAC9	KAT5	Q92993	987
HDAC9	FOXP3	Q9BZS1	942
HDAC9	EP300	Q09472	929
HDAC9	HDAC1	Q13547	929
HDAC9	NCOR1	O75376	918
HDAC9	SMARCA4	P51532	906
HDAC9	FOXA1	P55317	881
HDAC9	MEF2D	Q14814	874
HDAC9	MEF2A	Q02078	874
HDAC9	MEF2C	Q06413	818
HDAC9	NCOR2	Q9Y618	812
HDAC9	SIRT1	Q96EB6	799
HDAC9	CABIN1	Q9Y6J0	796
HDAC9	HIF1A	Q16665	778
HDAC9	BCL6	P41182	754

IntAct

22 interactions, top by confidence:

A	B	Type	Score
BCL6	HDAC9	psi-mi:“MI:0915”(physical association)	0.560
USF1	PARP1	psi-mi:“MI:0914”(association)	0.560
MEF2C	HDAC9	psi-mi:“MI:0915”(physical association)	0.550
ANKRA2	HDAC9	psi-mi:“MI:0407”(direct interaction)	0.440
ETV6	HDAC9	psi-mi:“MI:0915”(physical association)	0.400
NCOR1	HDAC9	psi-mi:“MI:0915”(physical association)	0.400
FOXP3	HDAC9	psi-mi:“MI:0915”(physical association)	0.400
HDAC9		psi-mi:“MI:0915”(physical association)	0.370
USF1	SREBF1	psi-mi:“MI:0914”(association)	0.350
SLC16A11	ESYT2	psi-mi:“MI:0914”(association)	0.350
HDAC9	IGLL5	psi-mi:“MI:0914”(association)	0.350
HDAC9	ZC3H11A	psi-mi:“MI:0914”(association)	0.350
BCL6	CACNA1A	psi-mi:“MI:0914”(association)	0.350
tkt1	HDAC9	psi-mi:“MI:0915”(physical association)	0.000
MEF2C	HDAC9	psi-mi:“MI:0915”(physical association)	0.000
HDAC9	YWHAE	psi-mi:“MI:0915”(physical association)	0.000
WNK1	HDAC9	psi-mi:“MI:0915”(physical association)	0.000
NRIP1	HDAC9	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (103): CTBP1 (Reconstituted Complex), HDAC9 (Affinity Capture-Western), HDAC9 (Co-localization), HDAC9 (Affinity Capture-Western), HDAC9 (Affinity Capture-Western), HDAC9 (Affinity Capture-Western), HDAC6 (Affinity Capture-Western), HIST4H4 (Biochemical Activity), HIST2H3A (Biochemical Activity), HDAC3 (Reconstituted Complex), SIN3A (Reconstituted Complex), SIN3B (Reconstituted Complex), NCOR1 (Reconstituted Complex), NCOR1 (Affinity Capture-Western), ETV6 (Affinity Capture-Western)

ESM2 similar proteins: A0A8M9QN10, A2ARM1, A6QL70, E7F654, O08653, O15178, O43147, P20293, P23611, P33242, P50569, P56524, P59114, P79779, P87377, P97499, Q02556, Q04752, Q0VD00, Q15306, Q1LVK9, Q28HY0, Q2M1K5, Q32N92, Q4VC12, Q5U263, Q64287, Q6DHF9, Q6NZM9, Q6NZR5, Q6P1Z5, Q6ZUJ8, Q7Z3E5, Q80U12, Q80U38, Q8BGX1, Q8C2B3, Q8R151, Q96HM7, Q96SI1

Diamond homologs: A0A8I6GM68, D2HBJ8, F1QCV2, O17323, O27262, O30107, P28606, P38748, P53973, P56523, P56524, P72702, P83038, Q09440, Q0V9G5, Q20296, Q2QWU2, Q3JUN4, Q54QE6, Q569C4, Q57955, Q5A960, Q5R902, Q5XGZ2, Q613L4, Q6NTR6, Q6NZM9, Q6P3E7, Q6P9L4, Q70CQ1, Q70I53, Q7Z569, Q7ZUM8, Q80ZH1, Q8C2B3, Q8C2S0, Q8GXJ1, Q8LRK8, Q8RX28, Q8WUI4

SIGNOR signaling

17 interactions.

A	Effect	B	Mechanism
AURKB	down-regulates	HDAC9	phosphorylation
HDAC9	down-regulates	MEF2C	binding
DYRK1B	down-regulates	HDAC9	phosphorylation
belinostat	“down-regulates activity”	HDAC9	“chemical inhibition”
panobinostat	“down-regulates activity”	HDAC9	“chemical inhibition”
entinostat	“down-regulates activity”	HDAC9	“chemical inhibition”
vorinostat	“down-regulates activity”	HDAC9	“chemical inhibition”
N-hydroxy-3-[4-[[2-hydroxyethyl-[2-(1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide	“down-regulates activity”	HDAC9	“chemical inhibition”
“trichostatin A”	“down-regulates activity”	HDAC9	“chemical inhibition”
“N-[4-[(hydroxyamino)-oxomethyl]phenyl]carbamic acid [6-(diethylaminomethyl)-2-naphthalenyl]methyl ester”	“down-regulates activity”	HDAC9	“chemical inhibition”
romidepsin	“down-regulates activity”	HDAC9	“chemical inhibition”
6-(1,3-dioxo-2-benzo[de]isoquinolinyl)-N-hydroxyhexanamide	“down-regulates activity”	HDAC9	“chemical inhibition”
CUDC-101	“down-regulates activity”	HDAC9	“chemical inhibition”

Disease & clinical

Cancer significance

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	2
Likely pathogenic	1
Uncertain significance	104
Likely benign	10
Benign	11

Top pathogenic / likely-pathogenic (3)

Variant ID	HGVS	Classification
2580891	NC_000007.14:g.18437239_18867540dup	Pathogenic
58533	GRCh38/hg38 7p21.1(chr7:17930595-18209019)x1	Pathogenic
2664509	GRCh37/hg19 7p21.1(chr7:17930686-19059254)x1	Likely pathogenic

SpliceAI

1865 predictions. Top by Δscore:

Variant	Effect	Δscore
7:18545091:TTCCA:T	donor_gain	1.0000
7:18545099:T:G	donor_gain	1.0000
7:18585270:T:A	acceptor_gain	1.0000
7:18585279:A:AG	acceptor_gain	1.0000
7:18585279:AGT:A	acceptor_gain	1.0000
7:18585279:AGTG:A	acceptor_gain	1.0000
7:18585280:G:GA	acceptor_gain	1.0000
7:18585280:GT:G	acceptor_gain	1.0000
7:18585280:GTG:G	acceptor_gain	1.0000
7:18585280:GTGG:G	acceptor_gain	1.0000
7:18585280:GTGGA:G	acceptor_gain	1.0000
7:18590330:C:A	acceptor_gain	1.0000
7:18590333:A:AG	acceptor_gain	1.0000
7:18590333:AAGTT:A	acceptor_gain	1.0000
7:18590334:A:G	acceptor_gain	1.0000
7:18590420:G:GT	donor_gain	1.0000
7:18590483:GAAA:G	donor_gain	1.0000
7:18590487:G:GG	donor_gain	1.0000
7:18591643:G:GG	donor_gain	1.0000
7:18593902:TTCTA:T	acceptor_loss	1.0000
7:18593906:A:AG	acceptor_gain	1.0000
7:18593906:A:C	acceptor_loss	1.0000
7:18593906:AG:A	acceptor_gain	1.0000
7:18593906:AGG:A	acceptor_gain	1.0000
7:18593907:G:GA	acceptor_gain	1.0000
7:18593907:GG:G	acceptor_gain	1.0000
7:18593907:GGG:G	acceptor_gain	1.0000
7:18593907:GGGC:G	acceptor_gain	1.0000
7:18593907:GGGCT:G	acceptor_gain	1.0000
7:18594025:AACTG:A	donor_gain	1.0000

AlphaMissense

0 scored. Top likely-pathogenic:

dbSNP variants (sampled 300 via entrez): RS1000004144 (7:18860205 G>A), RS1000006070 (7:18102715 C>G), RS1000007167 (7:18260638 A>G), RS1000009370 (7:18928098 GTC>G), RS1000010435 (7:18187723 T>C), RS1000018239 (7:18347551 T>C), RS1000019654 (7:18227028 C>T), RS1000023545 (7:18408360 G>A), RS1000025672 (7:18114627 A>G,T), RS1000030958 (7:18525909 T>G), RS1000033275 (7:18232631 C>T), RS1000036767 (7:18114890 C>G,T), RS1000042514 (7:18154149 A>G), RS1000046846 (7:18545378 G>A), RS1000051327 (7:18828155 T>C)

Disease associations

OMIM: gene MIM:606543 | disease phenotypes: MIM:620457

GenCC curated gene-disease

Disease	Classification	Inheritance
auriculocondylar syndrome 4	Limited	Autosomal dominant
auriculocondylar syndrome	Disputed Evidence	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
auriculocondylar syndrome	Disputed	AD

Mondo (4): auriculocondylar syndrome 4 (MONDO:0957543), syndromic craniosynostosis (MONDO:0015338), syndromic intellectual disability (MONDO:0000508), auriculocondylar syndrome (MONDO:0000107)

Orphanet (2): Syndromic craniosynostosis (Orphanet:139393), Rare genetic syndromic intellectual disability (Orphanet:183763)

HPO phenotypes

13 total (13 of 13 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000160	Narrow mouth
HP:0000162	Glossoptosis
HP:0000175	Cleft palate
HP:0000293	Full cheeks
HP:0000324	Facial asymmetry
HP:0000347	Micrognathia
HP:0000365	Hearing impairment
HP:0001263	Global developmental delay
HP:0002104	Apnea
HP:0003577	Congenital onset
HP:0004451	Postauricular skin tag
HP:0030022	Question mark ear

GWAS associations

87 associations (top):

Study	Trait	p-value
GCST000853_4	Ulcerative colitis	2.000000e-06
GCST001400_1	Stroke	2.000000e-11
GCST001548_2	Male-pattern baldness	1.000000e-12
GCST001706_1	Stroke (ischemic)	4.000000e-06
GCST001706_2	Stroke (ischemic)	2.000000e-16
GCST001762_203	Obesity-related traits	7.000000e-06
GCST001762_658	Obesity-related traits	8.000000e-06
GCST001854_4	Retinopathy in non-diabetics	8.000000e-06
GCST002288_4	Large artery stroke	3.000000e-12
GCST002290_3	Coronary artery disease or large artery stroke	3.000000e-12
GCST002363_16	Response to anti-retroviral therapy (ddI/d4T) in HIV-1 infection (Grade 3 peripheral neuropathy)	2.000000e-08
GCST002588_7	Cerebral amyloid angiopathy	9.000000e-06
GCST002934_23	Zinc levels	9.000000e-06
GCST002949_5	Epilepsy and lamotrigine-induced maculopapular eruptions	2.000000e-07
GCST002987_2	Stroke	4.000000e-07
GCST003116_30	Coronary artery disease	8.000000e-11
GCST003154_2	Peripheral artery disease	8.000000e-08
GCST003258_3	Ischemic stroke	9.000000e-10
GCST003259_2	Ischemic stroke (large artery atherosclerosis)	5.000000e-09
GCST003274_9	Pulse pressure	4.000000e-11
GCST003542_192	Night sleep phenotypes	3.000000e-06
GCST003771_13	Loneliness	3.000000e-06
GCST003815_117	Late-onset Alzheimer’s disease	9.000000e-06
GCST003983_4	Male-pattern baldness	1.000000e-36
GCST003996_40	Monobrow	7.000000e-16
GCST004025_4	Systemic juvenile idiopathic arthritis	3.000000e-07
GCST004125_22	Type 2 diabetes (age of onset)	2.000000e-06
GCST004607_153	Plateletcrit	2.000000e-14
GCST004775_25	Pulse pressure	4.000000e-06
GCST004787_36	Coronary artery disease (myocardial infarction, percutaneous transluminal coronary angioplasty, coronary artery bypass grafting, angina or chromic ischemic heart disease)	3.000000e-13

EFO canonical traits (26, from GWAS)

EFO ID	Trait name
EFO:0004340	body mass index
EFO:0003940	physical activity
EFO:0000180	HIV-1 infection
EFO:1001253	maculopapular eruption
EFO:0005763	pulse pressure measurement
EFO:0007865	loneliness measurement
EFO:1001870	late-onset Alzheimers disease
EFO:0007906	synophrys measurement
EFO:0007985	platelet crit
EFO:0006797	neurofibrillary tangles measurement
EFO:0006798	neuritic plaque measurement
EFO:0004357	electroencephalogram measurement
EFO:0004350	reasoning
EFO:0006335	systolic blood pressure
EFO:0009764	eye colour measurement
EFO:0006917	spontaneous preterm birth
EFO:0010103	response to peginterferon alfa-2a
EFO:0007006	depressive symptom measurement
EFO:0010272	abdominal aortic calcification measurement
EFO:0004771	visual cortical surface area measurement
EFO:0004346	neuroimaging measurement
EFO:0008255	particulate matter air pollution measurement
EFO:0004980	appendicular lean mass
EFO:0004528	mean corpuscular hemoglobin concentration
EFO:0007984	platelet component distribution width
EFO:0004309	platelet count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
C538270	Auriculo-condylar syndrome (supp.)

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (4): CHEMBL2093865 (PROTEIN FAMILY), CHEMBL4145 (SINGLE PROTEIN), CHEMBL5169076 (PROTEIN-PROTEIN INTERACTION), CHEMBL5465556 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

28 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 448,227 (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
CHEMBL118	CELECOXIB	4	112,844
CHEMBL1469	PHENYLBUTANOIC ACID	4	37,081
CHEMBL1746	SODIUM PHENYLBUTYRATE	4	5,577
CHEMBL343448	ROMIDEPSIN	4	12,963
CHEMBL408513	BELINOSTAT	4	7,765
CHEMBL483254	PANOBINOSTAT	4	11,666
CHEMBL98	VORINOSTAT	4	50,361
CHEMBL1213492	GIVINOSTAT	4	2,827
CHEMBL140	CURCUMIN	3	93,882
CHEMBL145	CAFFEIC ACID	3	36,305
CHEMBL1851943	PRACINOSTAT	3	1,998
CHEMBL235191	TACEDINALINE	3	2,950
CHEMBL27759	ENTINOSTAT	3	6,584
CHEMBL3621988	TUCIDINOSTAT	3	2,182
CHEMBL2103863	ABEXINOSTAT	3	2,195
CHEMBL51085	EBSELEN	3	13,237
CHEMBL1801250	NANATINOSTAT	2	754
CHEMBL191482	AR-42	2	2,061
CHEMBL284616	CHLOROGENIC ACID	2	41,945
CHEMBL356066	DACINOSTAT	2	3,050
CHEMBL3622533	FIMEPINOSTAT	2
CHEMBL2105763	QUISINOSTAT	2
CHEMBL4283683	DOMATINOSTAT	2
CHEMBL353581	PYROXAMIDE	1
CHEMBL598797	CUDC-101	1
CHEMBL609583	R-306465	1
CHEMBL96	GAMMA-AMINOBUTYRIC ACID	1
CHEMBL99	TRICHOSTATIN	1

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 (13 total), top 13:

Ligand	Action	Affinity	Parameter
panobinostat	Inhibition	8.52	pEC50
TMP269	Inhibition	7.64	pIC50
quisinostat	Inhibition	7.49	pIC50
vorinostat	Inhibition	7.19	pKi
CUDC-101	Inhibition	7.17	pIC50
belinostat	Inhibition	6.6	pKi
givinostat	Inhibition	6.41	pKi
entinostat	Inhibition	6.3	pEC50
KA1010	Inhibition	6.25	pIC50
trichostatin A	Inhibition	6.1	pKi
romidepsin	Inhibition	5.96	pKi
scriptaid	Inhibition	5.1	pKi
dacinostat	Inhibition	5.05	pKi

Binding affinities (BindingDB)

135 measured of 146 human assays (147 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
(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
(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
(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
(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
R-TSA	IC50	5.76 nM
HDAC inhibitor, Compound 2	IC50	7.93 nM
HDAC inhibitor, Compound 1	IC50	10.1 nM
(S)-1-(2,6-Difluorophenyl)-5-(3-fluoro-2- methylphenyl)-N-hydroxy-1,4,5,6- tetrahydrocyclopenta[c]pyrazole-5-carboxamide	IC50	12 nM	US-10065948: Histone deacetylase inhibitors and compositions and methods of use thereof
(S)-1-(2-Chlorophenyl)-5-(3-fluoro-2-methylphenyl)- N-hydroxy-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-5- carboxamide	IC50	15 nM	US-10065948: Histone deacetylase inhibitors and compositions and methods of use thereof
(S)-1-(2-Chloro-6-fluorophenyl)-5-(3-fluoro-2- methylphenyl)-N-hydroxy-1,4,5,6- tetrahydrocyclopenta[c]pyrazole-5-carboxamide	IC50	15 nM	US-10065948: Histone deacetylase inhibitors and compositions and methods of use thereof
(S)-5-(3-Fluoro-2-methylphenyl)-l-(2-fluorophenyl)- N-hydroxy-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-5- carboxamide	IC50	17 nM	US-10065948: Histone deacetylase inhibitors and compositions and methods of use thereof
(S)-1-(3-Chloro-2-fluorophenyl)-5-(3-fluoro-2- methylphenyl)-N-hydroxy-1,4,5,6- tetrahydrocyclopenta[c]pyrazole-5-carboxamide	IC50	17 nM	US-10065948: Histone deacetylase inhibitors and compositions and methods of use thereof
(E)-N-hydroxy-3-[3-[methyl(phenyl)sulfamoyl]phenyl]prop-2-enamide	IC50	17.8 nM	US-10188756: Imaging histone deacetylases with a radiotracer using positron emission tomography
(S)-5-(3-Fluoro-2-methylphenyl)-1-(2-fluoro-6- methylphenyl)-N-hydroxy-1,4,5,6- tetrahydrocyclopenta[c]pyrazole-5-carboxamide	IC50	19 nM	US-10065948: Histone deacetylase inhibitors and compositions and methods of use thereof
(S)-1-(2,5-Dimethylphenyl)-5-(3-fluoro-2- methylphenyl)-N-hydroxy-1,4,5,6- tetrahydrocyclopenta[c]pyrazole-5-carboxamide	IC50	21 nM	US-10065948: Histone deacetylase inhibitors and compositions and methods of use thereof
(S)-5-(3-Fluoro-2-methylphenyl)-N-hydroxy-l-(o- tolyl)-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-5- carboxamide	IC50	23 nM	US-10065948: Histone deacetylase inhibitors and compositions and methods of use thereof
(E)-3-[3-[(1-adamantylamino)methyl]phenyl]-N-hydroxyprop-2-enamide	IC50	24 nM	US-10188756: Imaging histone deacetylases with a radiotracer using positron emission tomography
(S)-1-(2,6-Dimethylphenyl)-5-(3-fluoro-2- methylphenyl)-N-hydroxy-1,4,5,6- tetrahydrocyclopenta[c]pyrazole-5-carboxamide	IC50	27 nM	US-10065948: Histone deacetylase inhibitors and compositions and methods of use thereof
(R)-1-Benzyl-4-(3-fluoro-2-methylphenyl)-N-hydroxy- 1,4,5,6-tetrahydrocyclopenta[c]pyrazole-4- carboxamide	IC50	27 nM	US-10065948: Histone deacetylase inhibitors and compositions and methods of use thereof
(S)-5-(3-Fluoro-2-methylphenyl)-N-hydroxy-1-phenyl- l,4,5,6-tetrahydrocyclopenta[c]pyrazole-5- carboxamide	IC50	28 nM	US-10065948: Histone deacetylase inhibitors and compositions and methods of use thereof
(S)-5-(3-Fluoro-2-methylphenyl)-N-hydroxy-1-(m- tolyl)-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-5- carboxamide	IC50	28 nM	US-10065948: Histone deacetylase inhibitors and compositions and methods of use thereof
(S)-1-(2,4-Difluorophenyl)-5-(3-fluoro-2- methylphenyl)-N-hydroxy-1,4,5,6- tetrahydrocyclopenta[c]pyrazole-5-carboxamide	IC50	29 nM	US-10065948: Histone deacetylase inhibitors and compositions and methods of use thereof
(S)-5-(3-Fluoro-2-methylphenyl)-1-(5-fluoropyridin-2- yl)-N-hydroxy-1,4,5,6- tetrahydrocyclopenta[c]pyrazole-5-carboxamide	IC50	31 nM	US-10065948: Histone deacetylase inhibitors and compositions and methods of use thereof
(S)-1-(2-Chloro-4-fluorophenyl)-5-(3-fluoro-2- methylphenyl)-N-hydroxy-1,4,5,6- tetrahydrocyclopenta[c]pyrazole-5-carboxamide	IC50	36 nM	US-10065948: Histone deacetylase inhibitors and compositions and methods of use thereof
(S)-1-Cyclopentyl-5-(3-fluoro-2-methylphenyl)-N- hydroxy-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-5- carboxamide	IC50	37 nM	US-10065948: Histone deacetylase inhibitors and compositions and methods of use thereof
(S)-5-(3-Fluoro-2-methylphenyl)-N-hydroxy-1- (pyrazin-2-yl)-1,4,5,6- tetrahydrocyclopenta[c]pyrazole-5-carboxamide	IC50	38 nM	US-10065948: Histone deacetylase inhibitors and compositions and methods of use thereof
(S)-5-(3-Fluoro-2-methylphenyl)-N-hydroxy-1-(p- tolyl)-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-5- carboxamide	IC50	39 nM	US-10065948: Histone deacetylase inhibitors and compositions and methods of use thereof
(S)-5-(3-Fluoro-2-methylphenyl)-1-(3-fluorophenyl)- N-hydroxy-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-5- carboxamide	IC50	44 nM	US-10065948: Histone deacetylase inhibitors and compositions and methods of use thereof
(S)-5-(3-Fluoro-2-methylphenyl)-1-(4-fluoro-2- methylphenyl)-N-hydroxy-1,4,5,6- tetrahydrocyclopenta[c]pyrazole-5-carboxamide	IC50	44 nM	US-10065948: Histone deacetylase inhibitors and compositions and methods of use thereof
(R)-5-(3-Fluoro-2-methylphenyl)-N-hydroxy-2-(1- methyl-1H-pyrazol-5-yl)-5,6-dihydro-4H- cyclopenta[d]thiazole-5-carboxamide	IC50	44 nM	US-10065948: Histone deacetylase inhibitors and compositions and methods of use thereof
(S)-1-Cyclopropyl-5-(3-fluoro-2-methylphenyl)-N- hydroxy-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-5- carboxamide	IC50	48 nM	US-10065948: Histone deacetylase inhibitors and compositions and methods of use thereof
(S)-1-Benzyl-5-(3-fluoro-2-methylphenyl)-N-hydroxy- 1,4,5,6-tetrahydrocyclopenta[c]pyrazole-5- carboxamide	IC50	48 nM	US-10065948: Histone deacetylase inhibitors and compositions and methods of use thereof
3-(furan-3-yl)-N-[[4-(hydroxycarbamoyl)phenyl]methyl]-5-(4-hydroxyphenyl)-1H-pyrrole-2-carboxamide	IC50	49.9 nM	US-8685992: Histone deacetylase inhibitors based simultaneously on trisubstituted 1H-pyrroles and aromatic and heteroaromatic spacers
(R)-5-(3-Fluoro-2-methylphenyl)-N-hydroxy-2-(5- fluoropyridin-2-yl)-5,6-dihydroxy-4H- cyclopenta[d]thiazole-5-carboxamide	IC50	51 nM	US-10065948: Histone deacetylase inhibitors and compositions and methods of use thereof
(S)-5-(3-Fluoro-2-methylphenyl)-1-(4-fluorophenyl)- N-hydroxy-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-5- carboxamide	IC50	53 nM	US-10065948: Histone deacetylase inhibitors and compositions and methods of use thereof
(S)-5-(3-Fluoro-2-methylphenyl)-N-hydroxy-2-(3- methylpyridin-4-yl)-2,4,5,6- tetrahydrocyclopenta[c]pyrazole-5-carboxamide	IC50	53 nM	US-10065948: Histone deacetylase inhibitors and compositions and methods of use thereof
(R)-5-(3-Fluoro-2-methylphenyl)-3-(4-fluorophenyl)- N-hydroxy-2-methyl-2,4,5,6- tetrahydrocyclopenta[c]pyrazole-5-carboxamide	IC50	53 nM	US-10065948: Histone deacetylase inhibitors and compositions and methods of use thereof
6-[[1-adamantylmethyl(methyl)amino]methyl]-N-hydroxy-3,4-dihydronaphthalene-2-carboxamide	IC50	55.8 nM	US-10188756: Imaging histone deacetylases with a radiotracer using positron emission tomography
(S)-5-(3-Fluoro-2-methylphenyl)-N-hydroxy-1-(3- methylpyridin-4-yl)-1,4,5,6- tetrahydrocyclopenta[c]pyrazole-5-carboxamide	IC50	57 nM	US-10065948: Histone deacetylase inhibitors and compositions and methods of use thereof
(S)-1-(3-Chlorophenyl)-5-(3-fluoro-2-methylphenyl)- N-hydroxy-1,4,5,6-tetrahydrocyclopenta[c]pyrazole-5- carboxamide	IC50	61 nM	US-10065948: Histone deacetylase inhibitors and compositions and methods of use thereof
N-hydroxy-7-[isoquinolin-3-yl(pyridin-2-yl)amino]heptanamide	IC50	64 nM	US-8748458: Scriptaid isosteres and their use in therapy

ChEMBL bioactivities

3530 potent at pChembl≥5 of 3904 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.77	IC50	0.17	nM	CHEMBL5433552
9.70	IC50	0.2	nM	CHEMBL2371007
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
9.52	IC50	0.3	nM	CHEMBL2370998
9.52	IC50	0.3	nM	CHEMBL5199116
9.52	IC50	0.3	nM	CHEMBL5170036
9.52	IC50	0.3	nM	CHEMBL1793822
9.46	IC50	0.35	nM	VORINOSTAT
9.40	IC50	0.4	nM	CHEMBL2371000
9.40	IC50	0.4	nM	CHEMBL1793816
9.30	IC50	0.5	nM	ENTINOSTAT
9.08	IC50	0.83	nM	PANOBINOSTAT
9.05	IC50	0.9	nM	CHEMBL3692689
9.05	IC50	0.9	nM	CHEMBL605110
9.02	IC50	0.95	nM	CHEMBL595479
9.00	IC50	1	nM	CHEMBL3758184
9.00	IC50	1	nM	APICIDIN
9.00	IC50	1	nM	CHEMBL2371003
9.00	IC50	1	nM	ROMIDEPSIN
9.00	IC50	1	nM	CHEMBL4467135
9.00	IC50	1	nM	VORINOSTAT
9.00	IC50	1	nM	CHEMBL595711
9.00	IC50	1	nM	CHEMBL595910
9.00	IC50	1	nM	CHEMBL1793947
9.00	IC50	1	nM	CHEMBL1793810
9.00	IC50	1	nM	CHEMBL1793823
8.99	IC50	1.03	nM	CHEMBL1214760
8.98	IC50	1.05	nM	CHEMBL594544
8.96	IC50	1.1	nM	CHEMBL2414098
8.92	IC50	1.2	nM	CHEMBL604796
8.92	IC50	1.2	nM	CHEMBL608416
8.92	IC50	1.2	nM	CHEMBL594544
8.92	Ki	1.2	nM	PANOBINOSTAT
8.89	IC50	1.3	nM	CHEMBL1793992
8.85	IC50	1.4	nM	CHEMBL99661
8.85	IC50	1.42	nM	TRICHOSTATIN
8.82	IC50	1.5	nM	TRICHOSTATIN
8.82	IC50	1.5	nM	CHEMBL5280445
8.82	IC50	1.5	nM	CHEMBL594743
8.82	IC50	1.5	nM	CHEMBL593846
8.82	IC50	1.5	nM	CHEMBL594542
8.77	IC50	1.7	nM	CHEMBL595908
8.74	IC50	1.8	nM	CHEMBL478727
8.74	IC50	1.8	nM	CHEMBL26159
8.74	IC50	1.8	nM	CHEMBL595910
8.72	IC50	1.9	nM	CHEMBL477093
8.70	IC50	2	nM	CHEMBL99392

PubChem BioAssay actives

2495 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
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
(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
(3S,6S,9S,12R)-3-[(2S)-butan-2-yl]-9-(7-hydroxy-6-oxooctyl)-6-[(1-methoxyindol-3-yl)methyl]-1,4,7,10-tetrazabicyclo[10.4.0]hexadecane-2,5,8,11-tetrone	90356: Inhibitory concentration against human Histone deacetylase in Hela cells	ic50	0.0003	uM
Vorinostat	2031064: Inhibition of HDAC in human HeLa cells nuclear extract incubated for 30 mins by multiplate reader analysis	ic50	0.0003	uM
pyridin-3-ylmethyl N-[[4-[(2-aminophenyl)carbamoyl]phenyl]methyl]carbamate	1740018: Inhibition of recombinant human HDAC9 using pan-HDAC substrate incubated for 3 hrs by fluorescence method	ic50	0.0005	uM
N-hydroxy-2-[4-[(E)-1-hydroxy-4-(4-phenylphenyl)but-3-en-2-yl]piperazin-1-yl]pyrimidine-5-carboxamide	454842: Inhibition of HDAC in human HeLa cells extractt	ic50	0.0009	uM
N-hydroxy-2-[4-[(E)-1-hydroxy-4-(4-methoxyphenyl)but-3-en-2-yl]piperazin-1-yl]pyrimidine-5-carboxamide	454842: Inhibition of HDAC in human HeLa cells extractt	ic50	0.0009	uM
N-hydroxy-2-[4-[(E)-1-hydroxy-4-phenylbut-3-en-2-yl]piperazin-1-yl]pyrimidine-5-carboxamide	454842: Inhibition of HDAC in human HeLa cells extractt	ic50	0.0010	uM
2-[4-[(E)-4-(4-fluorophenyl)-1-hydroxybut-3-en-2-yl]piperazin-1-yl]-N-hydroxypyrimidine-5-carboxamide	454842: Inhibition of HDAC in human HeLa cells extractt	ic50	0.0010	uM
(3S,6R,9S,12R)-3-[(2S)-butan-2-yl]-6-[(1-methoxyindol-2-yl)methyl]-9-(6-oxooctyl)-1,4,10-triazabicyclo[10.4.0]hexadecane-2,5,8,11-tetrone	1622995: Inhibition of HDAC (unknown origin)	ic50	0.0010	uM
N-hydroxy-6-[(2S,5S,8S,11S)-8-(1H-indol-3-ylmethyl)-2-methyl-11-(2-methylpropyl)-3,6,9,13-tetraoxo-1,4,7,10-tetrazacyclotridec-5-yl]hexanamide	447991: Inhibition of HDAC in human HeLa cell nuclear extract after 30 mins by fluorimetric assay	ic50	0.0010	uM
N-hydroxy-2-[4-[(E)-1-hydroxy-4-(4-methylphenyl)but-3-en-2-yl]piperazin-1-yl]pyrimidine-5-carboxamide	454842: Inhibition of HDAC in human HeLa cells extractt	ic50	0.0010	uM
6-[(5S,8S,11R)-11-[(2S)-butan-2-yl]-8-(1H-indol-2-ylmethyl)-3,6,9,13-tetraoxo-1,4,7,10-tetrazacyclotridec-5-yl]-N-hydroxyhexanamide	487230: Inhibition of HDAC in human HeLa cells	ic50	0.0010	uM
7-[4-[4-[[[(2S,3R,4S,6R)-2-[[(2R,4R,5R,6R,8R,11R,12S,19R,20R)-11-ethyl-4-methoxy-2,4,6,8,12,19-hexamethyl-7,9,14-trioxo-10,13-dioxa-15,18-diazatricyclo[10.6.2.015,20]icos-1(18)-en-5-yl]oxy]-3-hydroxy-6-methyloxan-4-yl]-methylamino]methyl]phenyl]triazol-1-yl]-N-hydroxyheptanamide	499799: Inhibition of HDAC in human HeLa cell nuclear extracts	ic50	0.0010	uM
(E)-N-hydroxy-3-[4-oxo-1’-(2-phenylethyl)spiro[3H-chromene-2,3’-piperidine]-6-yl]prop-2-enamide	1273866: Inhibition of HDAC in human HeLa cells nuclear extract using Fluor de lys as substrate after 15 mins by fluorometric analysis	ic50	0.0010	uM
2-[4-[(E)-4-(3-fluorophenyl)-1-hydroxybut-3-en-2-yl]piperazin-1-yl]-N-hydroxypyrimidine-5-carboxamide	454842: Inhibition of HDAC in human HeLa cells extractt	ic50	0.0012	uM
2-[4-[(E)-4-(4-chlorophenyl)-1-hydroxybut-3-en-2-yl]piperazin-1-yl]-N-hydroxypyrimidine-5-carboxamide	454842: Inhibition of HDAC in human HeLa cells extractt	ic50	0.0012	uM
N’-hydroxy-N-[(2R)-4-(methylamino)-3-oxo-1-phenylbutan-2-yl]octanediamide	90195: Concentration required to inhibit Histone Deacetylase (HDAC) from K562 erythroleukemia cells	ic50	0.0014	uM
(2E,4E,6R)-7-[4-(dimethylamino)phenyl]-N-hydroxy-4,6-dimethyl-7-oxohepta-2,4-dienamide	1273502: Inhibition of HDAC in human HeLa cell nuclear extract using BML-KI104 Fluor de Lys as substrate by fluorescence-based assay	ic50	0.0014	uM
N-hydroxy-2-[4-(naphthalen-2-ylmethyl)piperazin-1-yl]pyrimidine-5-carboxamide	454842: Inhibition of HDAC in human HeLa cells extractt	ic50	0.0015	uM
N-hydroxy-2-[4-[(E)-1-methoxy-4-phenylbut-3-en-2-yl]piperazin-1-yl]pyrimidine-5-carboxamide	454842: Inhibition of HDAC in human HeLa cells extractt	ic50	0.0015	uM
N-hydroxy-2-[4-[[[(E)-1-hydroxy-4-phenylbut-3-en-2-yl]amino]methyl]piperidin-1-yl]pyrimidine-5-carboxamide	454842: Inhibition of HDAC in human HeLa cells extractt	ic50	0.0015	uM
N-hydroxy-2-[4-[(E)-4-phenylbut-3-en-2-yl]piperazin-1-yl]pyrimidine-5-carboxamide	454842: Inhibition of HDAC in human HeLa cells extractt	ic50	0.0017	uM
N-hydroxy-6-[4-(6-methoxynaphthalen-2-yl)triazol-1-yl]hexanamide	382342: Inhibition of human HDAC in HeLa cells by flour de lys assay	ic50	0.0018	uM
N-hydroxy-6-[4-(3-phenylphenyl)triazol-1-yl]hexanamide	382342: Inhibition of human HDAC in HeLa cells by flour de lys assay	ic50	0.0019	uM
2-[2-[2-[[(2E)-3-(3-bromo-4-hydroxyphenyl)-2-hydroxyiminopropanoyl]amino]ethyldisulfanyl]ethylamino]-2-oxoacetic acid	90530: Inhibitory concentration against isolated Histone deacetylase	ic50	0.0020	uM
(3S,6S,9S,12R)-3-[(2S)-butan-2-yl]-6-(1H-indol-3-ylmethyl)-9-(6-oxooctyl)-1,4,7,10-tetrazabicyclo[10.4.0]hexadecane-2,5,8,11-tetrone	81887: Inhibitory activity against histone deacetylase (HDAC) enzyme derived from partially purified extracts of human HeLa cells using [3H]11 as radioligand	ic50	0.0020	uM
6-[4-[[5-chloro-4-(4-chloroanilino)pyrimidin-2-yl]amino]pyrazol-1-yl]-N-hydroxyhexanamide	1550094: Inhibition of HDAC in human HeLa nuclear extract using Boc-Lys(acetyl)-AMC as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by fluorescence assay	ic50	0.0020	uM
7-[4-[[5-chloro-4-(4-chloroanilino)pyrimidin-2-yl]amino]pyrazol-1-yl]-N-hydroxyheptanamide	1550094: Inhibition of HDAC in human HeLa nuclear extract using Boc-Lys(acetyl)-AMC as substrate preincubated for 5 mins followed by substrate addition and measured after 30 mins by fluorescence assay	ic50	0.0020	uM
4-[(E)-3-[[(2S)-1-(4-bromoanilino)-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-oxoprop-1-enyl]-N-hydroxybenzamide	1390020: Inhibition of HDAC in human HeLa cell nuclear extract using Boc-Lys (acetyl)-AMC as substrate preincubated for 5 mins followed by substrate addition measured after 30 mins by fluorescence assay	ic50	0.0020	uM
4-[(E)-3-[[(2S)-1-(4-fluoroanilino)-3-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-oxoprop-1-enyl]-N-hydroxybenzamide	1390020: Inhibition of HDAC in human HeLa cell nuclear extract using Boc-Lys (acetyl)-AMC as substrate preincubated for 5 mins followed by substrate addition measured after 30 mins by fluorescence assay	ic50	0.0020	uM
2-(6-ethoxy-3-pyridinyl)-N-[7-(hydroxyamino)-7-oxoheptyl]-9-(2-methoxy-3-pyridinyl)-8-oxo-7H-purine-6-carboxamide	2079009: Inhibition of HDAC in human HeLa cells nuclear extract	ic50	0.0020	uM
2-[4-[(E)-4-(2-fluorophenyl)-1-hydroxybut-3-en-2-yl]piperazin-1-yl]-N-hydroxypyrimidine-5-carboxamide	454842: Inhibition of HDAC in human HeLa cells extractt	ic50	0.0020	uM
N-hydroxy-7-[5-(4-methoxyphenyl)-1,3-oxazol-2-yl]heptanamide	316872: Inhibition of HDAC from human K562 cells	ic50	0.0021	uM
N-hydroxy-6-[4-(4-methoxyphenyl)triazol-1-yl]hexanamide	382342: Inhibition of human HDAC in HeLa cells by flour de lys assay	ic50	0.0021	uM
tert-butyl (8R,9R,12S)-12-[[6-(hydroxyamino)-6-oxohexyl]carbamoyl]-9-(2-methylpropyl)-2-oxa-11-azabicyclo[12.2.2]octadeca-1(16),14,17-triene-8-carboxylate	90195: Concentration required to inhibit Histone Deacetylase (HDAC) from K562 erythroleukemia cells	ic50	0.0021	uM
N-hydroxy-6-(4-quinolin-2-yltriazol-1-yl)hexanamide	382342: Inhibition of human HDAC in HeLa cells by flour de lys assay	ic50	0.0021	uM
N-hydroxy-2-[4-[(E)-1-hydroxy-4-[4-(trifluoromethyl)phenyl]but-3-en-2-yl]piperazin-1-yl]pyrimidine-5-carboxamide	454842: Inhibition of HDAC in human HeLa cells extractt	ic50	0.0021	uM
6-[4-(4-bromoanilino)-7-methoxyquinazolin-6-yl]oxy-N-hydroxyhexanamide	1720096: Inhibition of HDAC (unknown origin)	ic50	0.0022	uM
7-[4-(4-bromoanilino)-7-methoxyquinazolin-6-yl]oxy-N-hydroxyheptanamide	1275247: Inhibition of HDAC in human HeLa cell nuclear extracts preincubated for 15 mins followed by addition of Fluor de Lys as substrate for 1 hr by fluorometric assay	ic50	0.0022	uM
N-hydroxy-6-[4-(4-pyridin-4-ylphenyl)triazol-1-yl]hexanamide	382342: Inhibition of human HDAC in HeLa cells by flour de lys assay	ic50	0.0023	uM
N-hydroxy-7-[4-(4-methoxyphenyl)-1,3-thiazol-2-yl]heptanamide	316872: Inhibition of HDAC from human K562 cells	ic50	0.0025	uM
7-[5-(4-bromophenyl)-1,3-oxazol-2-yl]-N-hydroxyheptanamide	316872: Inhibition of HDAC from human K562 cells	ic50	0.0027	uM
(E)-N-hydroxy-3-[4-[2-(2-methyl-1H-indol-3-yl)ethylsulfamoyl]phenyl]prop-2-enamide	1187258: Inhibition of HDAC in human HeLa cells nuclear extracts incubated for 30 mins by fluorescent assay	ic50	0.0028	uM
6-[4-(2,4-dichloroanilino)-7-methoxyquinazolin-6-yl]oxy-N-hydroxyhexanamide	1256443: Inhibition of human HDAC in HeLa cell nuclear extract by fluorometric assay using Fluor de Lys substrate	ic50	0.0028	uM
7-[4-(2,4-dichloroanilino)-7-methoxyquinazolin-6-yl]oxy-N-hydroxyheptanamide	1915571: Inhibition of HDAC (unknown origin)	ic50	0.0028	uM
N-hydroxy-6-[[(E)-3-quinolin-7-ylprop-2-enoyl]amino]hexanamide	373082: Inhibition of human recombinant HDAC9	ic50	0.0028	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
sodium arsenite	affects cotreatment, increases abundance, increases expression	6
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases expression, increases methylation	5
trichostatin A	affects cotreatment, decreases expression	4
bisphenol A	affects methylation, decreases expression	3
(+)-JQ1 compound	affects cotreatment, decreases expression	3
Benzo(a)pyrene	affects methylation, increases expression	3
Cadmium Chloride	decreases expression, increases abundance, increases expression	3
entinostat	decreases expression, affects cotreatment	2
monomethylarsonous acid	decreases reaction, increases expression	2
Vorinostat	affects cotreatment, decreases expression, decreases reaction, increases expression	2
Estradiol	affects cotreatment, increases expression, decreases expression	2
Silicon Dioxide	increases expression	2
Aflatoxin B1	decreases methylation, increases methylation	2
aristolochic acid I	increases expression	1
FR900359	decreases phosphorylation	1
bisphenol F	affects cotreatment, decreases methylation	1
TAK-243	decreases sumoylation	1
methylmercuric chloride	decreases expression	1
oxybenzone	increases expression	1
titanium dioxide	decreases expression	1
malealdehyde	affects expression	1
mono-(2-ethylhexyl)phthalate	decreases expression	1
sulforaphane	decreases expression	1
benzo(e)pyrene	decreases methylation	1
ferrous chloride	increases expression	1
hydroquinone	increases expression	1
diallyl trisulfide	increases expression	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	affects expression	1
brequinar	increases expression	1
astragaloside A	decreases reaction, increases reaction, increases expression, increases phosphorylation, decreases expression	1

ChEMBL screening assays

1625 unique, capped per target: 1612 binding, 8 admet, 4 functional, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1003756	Binding	Inhibition of HDAC in human NB4 cells assessed as induction of histone H3 acetylation after 6 hrs by Western blot analysis	Design, synthesis and preliminary biological evaluation of new hydroxamate histone deacetylase inhibitors as potential antileukemic agents. — Bioorg Med Chem Lett
CHEMBL4346553	ADMET	Inhibition of HDAC in HUVEC using Boc-Lys(Ac)-AMC as substrate preincubated for 12 hrs followed by substrate addition and measured after 4 hrs by fluorimetry	Discovery of Novel Fungal Lanosterol 14α-Demethylase (CYP51)/Histone Deacetylase Dual Inhibitors to Treat Azole-Resistant Candidiasis. — J Med Chem
CHEMBL5049470	Functional	In vivo inhibition of HDAC in HEL cells xenografted in BALB/C mouse assessed as upregulation of caspase-9 levels at 5 to 10 mg/kg by immunohistochemical staining method	Evodiamine-Inspired Topoisomerase-Histone Deacetylase Dual Inhibitors: Novel Orally Active Antitumor Agents for Leukemia Therapy. — J Med Chem

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SR22	HAP1 HDAC9 (-) 1	Cancer cell line	Male
CVCL_SR23	HAP1 HDAC9 (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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