NCOR2

Summary

NCOR2 (nuclear receptor corepressor 2, HGNC:7673) is a protein-coding gene on chromosome 12q24.31, encoding Nuclear receptor corepressor 2 (Q9Y618). Transcriptional corepressor that mediates the transcriptional repression activity of some nuclear receptors by promoting chromatin condensation, thus preventing access of the basal transcription.

This gene encodes a nuclear receptor co-repressor that mediates transcriptional silencing of certain target genes. The encoded protein is a member of a family of thyroid hormone- and retinoic acid receptor-associated co-repressors. This protein acts as part of a multisubunit complex which includes histone deacetylases to modify chromatin structure that prevents basal transcriptional activity of target genes. Aberrant expression of this gene is associated with certain cancers. Alternate splicing results in multiple transcript variants encoding different isoforms.

Source: NCBI Gene 9612 — RefSeq curated summary.

At a glance

• GWAS associations: 25
• Clinical variants (ClinVar): 649 total — 1 likely-pathogenic
• Druggable target: yes — 15 molecules with ChEMBL bioactivity
• Cancer driver (intOGen): loss-of-function (tumor-suppressor-like) across 8 cancer types
• Transcription factor: yes — 76 downstream targets (CollecTRI)
• MANE Select transcript: NM_006312

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:7673
Approved symbol	NCOR2
Name	nuclear receptor corepressor 2
Location	12q24.31
Locus type	gene with protein product
Status	Approved
Aliases	SMRT, SMRTE, TRAC-1, CTG26, TNRC14
Ensembl gene	ENSG00000196498
Ensembl biotype	protein_coding
OMIM	600848
Entrez	9612

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 19 protein_coding, 9 retained_intron

ENST00000404621, ENST00000405201, ENST00000413172, ENST00000418829, ENST00000420698, ENST00000429285, ENST00000440187, ENST00000440337, ENST00000443451, ENST00000448008, ENST00000448614, ENST00000453428, ENST00000458234, ENST00000461081, ENST00000464377, ENST00000473999, ENST00000474079, ENST00000493859, ENST00000494460, ENST00000536195, ENST00000542565, ENST00000542927, ENST00000938315, ENST00000938316, ENST00000938317, ENST00000938318, ENST00000938319, ENST00000938320

RefSeq mRNA: 3 — MANE Select: NM_006312 NM_001077261, NM_001206654, NM_006312

CCDS: CCDS41857, CCDS41858, CCDS55892

Canonical transcript exons

ENST00000405201 — 49 exons

Exon	Start	End
ENSE00000939871	124336753	124337180
ENSE00000939872	124335483	124335632
ENSE00000939873	124335135	124335280
ENSE00000939874	124334424	124334617
ENSE00000939876	124332319	124332467
ENSE00000939878	124327409	124327633
ENSE00000997027	124340006	124340204
ENSE00000997028	124340602	124340751
ENSE00000997033	124374413	124374463
ENSE00000997044	124340294	124340443
ENSE00001550226	124324415	124325583
ENSE00001554329	124356642	124356782
ENSE00002217548	124385745	124385887
ENSE00002219103	124362126	124362297
ENSE00002220966	124343005	124343226
ENSE00002220990	124422501	124422555
ENSE00002230621	124378237	124378384
ENSE00002235267	124354478	124354582
ENSE00002241469	124344597	124344951
ENSE00002245235	124347825	124347911
ENSE00002248577	124350587	124350737
ENSE00002257694	124398119	124398181
ENSE00002260798	124402404	124402561
ENSE00002261739	124354093	124354196
ENSE00002261915	124341823	124342074
ENSE00002263223	124400501	124400673
ENSE00002268512	124348174	124348314
ENSE00002283622	124363679	124363799
ENSE00002288378	124419957	124420055
ENSE00002296206	124346564	124346850
ENSE00002309098	124372022	124372610
ENSE00003510852	124426622	124426800
ENSE00003516815	124457106	124457162
ENSE00003531452	124430615	124430787
ENSE00003546707	124466173	124466286
ENSE00003583176	124355432	124355571
ENSE00003584505	124437930	124437996
ENSE00003608716	124449815	124449867
ENSE00003630710	124483596	124483773
ENSE00003636199	124472952	124473131
ENSE00003638701	124354837	124354939
ENSE00003652526	124495147	124495368
ENSE00003669212	124333130	124333279
ENSE00003671407	124486441	124486568
ENSE00003672076	124429613	124429706
ENSE00003727357	124326191	124326370
ENSE00003745626	124330845	124330898
ENSE00003973588	124535565	124535611
ENSE00003973589	124567308	124567612

Expression profiles

Bgee: expression breadth ubiquitous, 293 present calls, max score 99.16.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 35.2201 / max 808.5431, expressed in 1804 samples.

FANTOM5 promoters (21 alternative TSS)

Promoter ID	TPM avg	Samples expressed
133988	12.7118	1284
133991	7.6180	1193
134020	6.4665	1723
134016	1.3940	462
133996	1.0755	490
134013	1.0339	521
134012	0.9303	536
133982	0.7309	372
134014	0.7161	412
133995	0.5550	329

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
sural nerve	UBERON:0015488	99.16	gold quality
adenohypophysis	UBERON:0002196	98.40	gold quality
pituitary gland	UBERON:0000007	98.36	gold quality
endocervix	UBERON:0000458	97.69	gold quality
parotid gland	UBERON:0001831	97.55	gold quality
right ovary	UBERON:0002118	97.55	gold quality
tibial nerve	UBERON:0001323	97.52	gold quality
left uterine tube	UBERON:0001303	97.50	gold quality
left ovary	UBERON:0002119	97.50	gold quality
body of uterus	UBERON:0009853	97.45	gold quality
hindlimb stylopod muscle	UBERON:0004252	97.39	gold quality
right hemisphere of cerebellum	UBERON:0014890	97.33	gold quality
mucosa of stomach	UBERON:0001199	97.21	gold quality
upper lobe of left lung	UBERON:0008952	97.03	gold quality
cerebellar hemisphere	UBERON:0002245	96.92	gold quality
upper lobe of lung	UBERON:0008948	96.85	gold quality
cerebellar cortex	UBERON:0002129	96.84	gold quality
right lung	UBERON:0002167	96.81	gold quality
gastrocnemius	UBERON:0001388	96.70	gold quality
lower esophagus muscularis layer	UBERON:0035833	96.65	gold quality
lower esophagus	UBERON:0013473	96.63	gold quality
muscle layer of sigmoid colon	UBERON:0035805	96.59	gold quality
muscle of leg	UBERON:0001383	96.56	gold quality
ectocervix	UBERON:0012249	96.55	gold quality
ovary	UBERON:0000992	96.53	gold quality
cerebellum	UBERON:0002037	96.48	gold quality
skin of leg	UBERON:0001511	96.45	gold quality
esophagogastric junction muscularis propria	UBERON:0035841	96.44	gold quality
saliva-secreting gland	UBERON:0001044	96.40	gold quality
minor salivary gland	UBERON:0001830	96.39	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	13.89

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

76 targets.

Target	Regulation
ABCA1	Activation
ACHE
ADAM2
AKT1
ALG3
APP
AR	Activation
BCOR
CCNB1
CCND1
CCR4
CDKN1A
CDKN2B
CEL
CHEK2
CIC
CNOT2
CREBBP
CRH
CYP1A1
CYP24A1
CYP3A4	Repression
DIO1
EBP
ESR1
FOLR1	Repression
GSTA2	Repression
HMGCS2	Repression
IGF1	Unknown
IL12B

Upstream regulators (CollecTRI, top): HIF1A, NCOR1, NCOR2, NFKB1, NR0B1, NR1I2, NR5A2, RBPJ, RELA, SPEN

miRNA regulators (miRDB)

55 targeting NCOR2, 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-3689D	100.00	66.14	1181
HSA-MIR-6851-5P	100.00	65.63	1294
HSA-MIR-4476	100.00	68.18	2030
HSA-MIR-200B-3P	100.00	73.31	2693
HSA-MIR-200C-3P	100.00	73.35	2685
HSA-MIR-429	100.00	73.44	2698
HSA-MIR-4510	100.00	66.60	2050
HSA-MIR-6127	100.00	66.76	2188
HSA-MIR-6129	100.00	66.46	2080
HSA-MIR-6130	100.00	66.69	2012
HSA-MIR-6133	100.00	66.48	2064
HSA-MIR-6876-5P	100.00	67.68	2126
HSA-MIR-3667-3P	99.99	67.17	1636
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-4728-5P	99.85	69.39	4718
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-4739	99.84	65.25	1832
HSA-MIR-1321	99.84	65.30	1811
HSA-MIR-4756-5P	99.84	64.98	1809
HSA-MIR-3663-3P	99.84	70.39	798
HSA-MIR-6785-5P	99.82	68.68	4428
HSA-MIR-4319	99.76	69.83	2586
HSA-MIR-149-3P	99.72	68.22	3963
HSA-MIR-6883-5P	99.69	68.05	3785
HSA-MIR-6887-3P	99.66	67.83	1778
HSA-MIR-3202	99.66	67.70	2737
HSA-MIR-6126	99.62	68.09	996
HSA-MIR-486-3P	99.51	66.82	1901
HSA-MIR-125A-5P	99.36	70.59	1640
HSA-MIR-125B-5P	99.36	70.36	1662

Literature-anchored findings (GeneRIF, showing 40)

• the effect of STAT5b-RARalpha on the activity of myeloid transcription factors including STAT3, and STAT5 as well as its molecular interactions with the nuclear receptor corepressor, SMRT, and nuclear receptor coactivator, TRAM-1. (PMID:11929748)
• Sstable binding of the Stat5-RARalpha fusion protein to corepressor SMRT is accompanied by an impaired response to differentiation signals in hematopoietic cells (PMID:11929749)
• Interactions that determine the assembly of a retinoid X receptor/corepressor complex (PMID:11972046)
• The silencing mediator of retinoic acid and thyroid hormone receptors can interact with the aryl hydrocarbon (Ah) receptor but fails to repress Ah receptor-dependent gene expression. (PMID:12139968)
• SMRT has a role as a coactivator for thyroid hormone receptor T3Ralpha from a negative hormone response element (PMID:12388540)
• a significant role of SMRT in modulating androgen receptor transcriptional activity (PMID:12441355)
• Differing transcriptional properties appear to reflect the differing abilities of the three RAR isotypes to interact with the SMRT corepressor protein. (PMID:12554770)
• SMRT and DAX-1 repress agonist-dependent activity of both androgen and progesterone receptors (PMID:12771131)
• SANT motif interprets the histone code and promotes histone deacetylation (PMID:12840002)
• Data describe a 17 residue fragment from SMRT that binds to the BCL6 BTB domain, and report the crystal structure of the complex to 2.2 angstroms. (PMID:14690607)
• differential recruitment of steroid receptor coactivator-1 and silencing mediator for retinoid and thyroid receptors by estrogen receptor-alpha and beta in breast cancer may be central to the response of the tumor to endocrine treatment (PMID:14715875)
• Elevated SMRT levels are common in prostate cancer cells, resulting in suppression of target genes associated with antiproliferative action. (PMID:15300237)
• SMRTbeta expression may influence the binding and transcriptional capacities of nuclear receptors in tumor cells (SMRTbeta) (PMID:15319284)
• differential mRNA splicing of SMRT serves to customize corepressor function in different cells, allowing the transcriptional properties of nuclear receptors to be adapted to different contexts (PMID:15632172)
• No significant allelic/genotypic association between any of the five mutations in SMRT/N-CoR2 and bipolar phenotype and the CAG repeat did not demonstrate allelic instability. (PMID:15635693)
• the subnuclear positioning of SMRT is influenced by the ligand-bound ERalpha, and this activity is dependent on the ratio of the co-expressed ERalpha and SMRT (PMID:15713534)
• N-CoR and SMRT play an active role in preventing tamoxifen from stimulating proliferation in breast cancer cells through repression of a subset of target genes involved in ERalpha function and cell proliferation (PMID:15802375)
• TRAC-1 (T cell RING protein identified in activation screen)is the first E3 ubiquitin ligase that serves a positive regulatory role in T cell activation. (PMID:15843525)
• SMRT and N-CoR corepressors are involved in transcriptional regulation by both agonist- and antagonist-bound AR and regulate the magnitude of hormone response, at least in part, by competing with coactivators. (PMID:16373395)
• The aryl hydrocarbon receptor activates the retinoic acid receptoralpha through SMRT antagonism (PMID:16480812)
• 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)
• expression of the silencing mediator of retinoid and thyroid receptor (SMRT) & histone deacetylase4 (HDAC4) enhances formation of Bach2 foci in nuclear matrix. SMRT mediates HDAC4 binding to Bach2, & HDAC4 facilitates retention of Bach2 in the foci. (PMID:17383980)
• NCOR2/SMRT is associated with poor patient outcome in breast cancer (PMID:17902051)
• These results would shed new insights for the molecular mechanisms of PML-RARalpha-associated leukemogenesis. (PMID:17991421)
• both SMRT and N-CoR are limited in cells and knocking down either of them results in co-repressor-free TR and consequently de-repression of TR target genes (PMID:18052923)
• Vitamin D receptor (VDR) with the retinoid X receptor (RXR) recruits NCoR and SMRT strictly in a VDR agonist-dependent manner. (PMID:18362166)
• CD40 signaling rapidly disrupts the ability of BCL6 to recruit the SMRT corepressor complex by excluding it from the nucleus, leading to histone acetylation, RNA polymerase II processivity, and activation of BCL6 target genes (PMID:18487509)
• Tamoxifen treatment of breast cancer cells reduced the expression of ER-alpha and increased the expression of SMRT. (PMID:18546531)
• SMRT and NCoR have important roles in the regulation of beta-catenin-TCF4-mediated gene transcription (PMID:18632669)
• SMRT protein stability is regulated by Pin1 and Cdk2. (PMID:18838553)
• These findings show that AR antagonists can enhance corepressor recruitment by stabilizing a distinct antagonist conformation of the AR coactivator/corepressor binding site. (PMID:18852122)
• Results indicate that the SMRT corepressor is directly involved in the vitamin D receptor-mediated repression in vivo via an ID1-specific interaction with the VDR. (PMID:19098224)
• Activated MEK signaling cascade inhibits functional recruitment of corepressor SMRT to cyproterone acetate-bound AR in prostate cancer cells. (PMID:19223455)
• SMRT function restoration induces JAG2 down-regulation as well as multipe myeloma apoptosis. (PMID:19417136)
• SMRT decreased with oestradiol treatment in human skeletal muscle cells (PMID:19432593)
• Both NCOR2 and CITED2 mRNA levels were associated with MFS, that is, tumour aggressiveness, independently of traditional prognostic factors. (PMID:19904269)
• These data link the SMRT corepressor directly with SRC family coactivators in positive regulation of ERalpha-dependent gene expression. (PMID:20392877)
• Aberrant expression and modification of SMRT might be involved in the pathogenesis of tumoral cortisol resistance. (PMID:20555024)
• Data report that SMRT interacts with itself to form a protein dimer, and that Erk2, a mitogen-activated protein (MAP) kinase, disrupts this SMRT self-dimerization in vitro and in vivo. (PMID:20965228)
• This study independently verifies the influence of NCOR2 and IDH1 on HIV transmission, and its findings suggest that variation in these genes affects susceptibility to HIV infection in exposed individuals. (PMID:21083371)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
danio_rerio	ncor2	ENSDARG00000000966
mus_musculus	Ncor2	ENSMUSG00000029478
rattus_norvegicus	Ncor2	ENSRNOG00000001004
caenorhabditis_elegans		WBGENE00001565

Paralogs (1): NCOR1 (ENSG00000141027)

Protein

Protein identifiers

Nuclear receptor corepressor 2 — Q9Y618 (reviewed: Q9Y618)

Alternative names: CTG repeat protein 26, SMAP270, Silencing mediator of retinoic acid and thyroid hormone receptor, T3 receptor-associating factor, Thyroid-, retinoic-acid-receptor-associated corepressor

All UniProt accessions (13): C9J0Q5, C9J330, C9JE98, C9JNV9, C9JQE8, Q9Y618, H0YGK8, H7BZU2, H7C0P3, H7C184, H7C1J7, H7C1Y3, H7C2R5

UniProt curated annotations — full annotation on UniProt →

Function. Transcriptional corepressor that mediates the transcriptional repression activity of some nuclear receptors by promoting chromatin condensation, thus preventing access of the basal transcription. Acts by recruiting chromatin modifiers, such as histone deacetylases HDAC1, HDAC2 and HDAC3. Required to activate the histone deacetylase activity of HDAC3. Involved in the regulation BCL6-dependent of the germinal center (GC) reactions, mainly through the control of the GC B-cells proliferation and survival. Recruited by ZBTB7A to the androgen response elements/ARE on target genes, negatively regulates androgen receptor signaling and androgen-induced cell proliferation. Isoform 1 and isoform 4 have different affinities for different nuclear receptors. Isoform 1 and isoform 4 have different affinities for different nuclear receptors.

Subunit / interactions. Forms a large corepressor complex that contains SIN3A/B and histone deacetylases HDAC1 and HDAC2. This complex associates with the thyroid (TR) and the retinoid acid receptors (RAR) in the absence of ligand, and may stabilize their interaction with TFIIB. Interacts directly with RARA in the absence of ligand; the interaction represses RARA activity. Interacts (isoform SMRT) with HDAC10. Interacts with MINT. Component of the N-Cor repressor complex, at least composed of NCOR1, NCOR2, HDAC3, TBL1X, TBL1R, CORO2A and GPS2. Interacts with CBFA2T3 and ATXN1L. Interacts with RARB; the interaction is weak and does not repress RARB transactivational activity. Interacts (via 1D-myo-inositol 1,4,5,6-tetrakisphosphate) with HDAC3; promoting the histone deacetylase activity of HDAC3. Interacts with HDAC7 and C1D. Interacts with NR4A2; this interaction increases in the absence of PITX3. Interacts with BCL6 (via the BTB domain), required for BCL6 transcriptional repressor activity on a subset of target genes. Forms ternary complexes with BCOR and BCL6 on target gene promoters but, on enhancer elements, interacts with BCL6 and HDAC3 to repress proximal gene expression. May interact with DEAF1. Interacts with RXRA. Interacts with MECP2. Interacts with ZBTB7A. Interacts with AR. Interacts with TBL1Y. Interacts with SANBR (via the BTB domain).

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous. High levels of expression are detected in lung, spleen and brain.

Domain organisation. The N-terminal region contains repression functions that are divided into three independent repression domains (RD1, RD2 and RD3). The C-terminal region contains the nuclear receptor-interacting domains that are divided in two separate interaction domains (ID1 and ID2). The two interaction domains (ID) contain a conserved sequence referred to as the CORNR box. This motif is required and sufficient to permit binding to unligated TR and RARS. Sequences flanking the CORNR box determine nuclear hormone receptor specificity. The deacetylase activation domain (DAD) promotes the recruitment and activation of HDAC3. Inositol tetraphosphate (1D-myo-inositol 1,4,5,6-tetrakisphosphate) acts as an intermolecular glue between HDAC3 and NCOR2.

Induction. Regulated during cell cycle progression.

Miscellaneous. Contains only the C-terminal receptor-interacting domain and acts as an antirepressor.

Similarity. Belongs to the N-CoR nuclear receptor corepressors family.

Isoforms (4)

UniProt ID	Names	Canonical?
Q9Y618-1	1, SMRT-alpha, TRAC-2, h-SMRT	yes
Q9Y618-2	2, TRAC-1
Q9Y618-4	3, SMRTe
Q9Y618-5	4, SMRT-tau

RefSeq proteins (3): NP_001070729, NP_001193583, NP_006303* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001005	SANT/Myb	Domain
IPR009057	Homeodomain-like_sf	Homologous_superfamily
IPR017884	SANT_dom	Domain
IPR017930	Myb_dom	Domain
IPR031557	N-CoR_GPS2_interact	Domain
IPR051571	N-CoR_corepressor	Family

Pfam: PF00249, PF15784

UniProt features (144 total): modified residue 45, compositionally biased region 22, region of interest 17, sequence conflict 16, helix 11, strand 7, turn 5, mutagenesis site 4, sequence variant 3, binding site 3, splice variant 3, domain 2, coiled-coil region 2, short sequence motif 2, chain 1, cross-link 1

Structure

Experimental structures (PDB)

36 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
8B94	X-RAY DIFFRACTION	1.55
8B92	X-RAY DIFFRACTION	1.66
8B95	X-RAY DIFFRACTION	1.72
8B8X	X-RAY DIFFRACTION	1.78
5ZOO	X-RAY DIFFRACTION	1.85
8B8W	X-RAY DIFFRACTION	1.86
8AQN	X-RAY DIFFRACTION	1.9
8B8Y	X-RAY DIFFRACTION	2
4A69	X-RAY DIFFRACTION	2.06
6PDZ	X-RAY DIFFRACTION	2.1
8B90	X-RAY DIFFRACTION	2.1
9XMJ	X-RAY DIFFRACTION	2.18
1R2B	X-RAY DIFFRACTION	2.2
5X8Q	X-RAY DIFFRACTION	2.2
8B93	X-RAY DIFFRACTION	2.21
8B8Z	X-RAY DIFFRACTION	2.22
8B91	X-RAY DIFFRACTION	2.23
8AQM	X-RAY DIFFRACTION	2.3
8X7E	X-RAY DIFFRACTION	2.3
6IVX	X-RAY DIFFRACTION	2.35
4OAR	X-RAY DIFFRACTION	2.41
9IWK	X-RAY DIFFRACTION	2.43
9IWJ	X-RAY DIFFRACTION	2.48
7SQA	X-RAY DIFFRACTION	2.5
6A22	X-RAY DIFFRACTION	2.55
5X8X	X-RAY DIFFRACTION	2.6
5ZOP	X-RAY DIFFRACTION	2.7
2GPV	X-RAY DIFFRACTION	2.85
3R29	X-RAY DIFFRACTION	2.9
1KKQ	X-RAY DIFFRACTION	3

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9Y618-F1	41.00	0.03

Functional residue map

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

Ligand- & substrate-binding residues (3): 449; 470; 471

Post-translational modifications (46): 18, 54, 67, 149, 152, 156, 215, 493, 553, 554, 750, 753, 878, 939, 946, 956, 959, 1173, 1210, 1240 …

Mutagenesis-validated functional residues (4):

Position	Phenotype
242–245	abolishes interaction with tbl1x.
2128	abolishes interaction with the apo lbd of rara. restores some interaction on the addition of inverse agonist bms493.
2130	abolishes interaction with the apo lbd of rara. no change on interaction on the addition of inverse agonist bms493.
2131	abolishes interaction with the apo lbd of rara. restores some interaction on the addition of inverse agonist bms493.

Function

Pathways and Gene Ontology

Reactome pathways

60 pathways

ID	Pathway
R-HSA-1989781	PPARA activates gene expression
R-HSA-2122947	NOTCH1 Intracellular Domain Regulates Transcription
R-HSA-2173795	Downregulation of SMAD2/3:SMAD4 transcriptional activity
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-383280	Nuclear Receptor transcription pathway
R-HSA-3899300	SUMOylation of transcription cofactors
R-HSA-400206	Regulation of lipid metabolism by PPARalpha
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-9623433	NR1H2 & NR1H3 regulate gene expression to control bile acid homeostasis
R-HSA-9707564	Cytoprotection by HMOX1
R-HSA-9841922	MLL4 and MLL3 complexes regulate expression of PPARG target genes in adipogenesis and hepatic steatosis
R-HSA-9976102	Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)
R-HSA-1266738	Developmental Biology
R-HSA-1430728	Metabolism
R-HSA-157118	Signaling by NOTCH
R-HSA-162582	Signal Transduction
R-HSA-1643685	Disease
R-HSA-170834	Signaling by TGF-beta Receptor Complex
R-HSA-1980143	Signaling by NOTCH1
R-HSA-212165	Epigenetic regulation of gene expression
R-HSA-212436	Generic Transcription Pathway
R-HSA-2173793	Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer
R-HSA-2262752	Cellular responses to stress

MSigDB gene sets: 344 (showing top): REACTOME_TRANSCRIPTIONAL_REGULATION_OF_WHITE_ADIPOCYTE_DIFFERENTIATION, PID_HDAC_CLASSI_PATHWAY, TGGTGCT_MIR29A_MIR29B_MIR29C, GOBP_HINDBRAIN_DEVELOPMENT, REACTOME_SIGNALING_BY_NOTCH, GOBP_METENCEPHALON_DEVELOPMENT, BUYTAERT_PHOTODYNAMIC_THERAPY_STRESS_DN, REACTOME_SIGNALING_BY_TGF_BETA_RECEPTOR_COMPLEX, GOBP_RESPONSE_TO_ESTRADIOL, GOBP_CELLULAR_RESPONSE_TO_LIPID, HSIAO_HOUSEKEEPING_GENES, GOBP_REGULATION_OF_INTRACELLULAR_STEROID_HORMONE_RECEPTOR_SIGNALING_PATHWAY, GOBP_KETONE_METABOLIC_PROCESS, GOBP_NEGATIVE_REGULATION_OF_INTRACELLULAR_SIGNAL_TRANSDUCTION, FERREIRA_EWINGS_SARCOMA_UNSTABLE_VS_STABLE_DN

GO Biological Process (10): negative regulation of transcription by RNA polymerase II (GO:0000122), lactation (GO:0007595), regulation of ketone metabolic process (GO:0010565), cerebellum development (GO:0021549), response to estradiol (GO:0032355), estrous cycle (GO:0044849), negative regulation of DNA-templated transcription (GO:0045892), negative regulation of androgen receptor signaling pathway (GO:0060766), negative regulation of miRNA transcription (GO:1902894), regulation of DNA-templated transcription (GO:0006355)

GO Molecular Function (12): DNA binding (GO:0003677), chromatin binding (GO:0003682), transcription corepressor activity (GO:0003714), Notch binding (GO:0005112), enzyme activator activity (GO:0008047), nuclear glucocorticoid receptor binding (GO:0035259), histone deacetylase binding (GO:0042826), protein-containing complex binding (GO:0044877), nuclear retinoid X receptor binding (GO:0046965), protein binding (GO:0005515), nuclear receptor binding (GO:0016922), nuclear retinoic acid receptor binding (GO:0042974)

GO Cellular Component (8): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), membrane (GO:0016020), nuclear matrix (GO:0016363), nuclear body (GO:0016604), transcription repressor complex (GO:0017053), protein-containing complex (GO:0032991)

Reactome top-level categories

Rollup of top-17 pathways:

Category	Pathways
Generic Transcription Pathway	2
NR1H2 and NR1H3-mediated signaling	2
Regulation of lipid metabolism by PPARalpha	1
Signaling by NOTCH1	1
Transcriptional activity of SMAD2/SMAD3:SMAD4 heterotrimer	1
Signaling by NOTCH1 PEST Domain Mutants in Cancer	1
Signaling by NOTCH1 HD+PEST Domain Mutants in Cancer	1
Chromatin modifying enzymes	1
Adipogenesis	1
SUMO E3 ligases SUMOylate target proteins	1
Metabolism of lipids	1
Loss of function of MECP2 in Rett syndrome	1
Transcriptional Regulation by MECP2	1
HCMV Infection	1
Cellular response to chemical stress	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
negative regulation of DNA-templated transcription	3
binding	3
DNA-templated transcription	2
nuclear receptor binding	2
nuclear lumen	2
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
body fluid secretion	1
mammary gland development	1
milk ejection reflex	1
regulation of metabolic process	1
ketone metabolic process	1
metencephalon development	1
anatomical structure development	1
response to lipid	1
response to oxygen-containing compound	1
ovulation cycle	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
androgen receptor signaling pathway	1
negative regulation of intracellular steroid hormone receptor signaling pathway	1
regulation of androgen receptor signaling pathway	1
miRNA transcription	1
regulation of miRNA transcription	1
negative regulation of miRNA metabolic process	1
regulation of gene expression	1
regulation of RNA biosynthetic process	1
nucleic acid binding	1
transcription coregulator activity	1
signaling receptor binding	1
catalytic activity	1
enzyme regulator activity	1
molecular function activator activity	1
enzyme binding	1
nuclear retinoic acid receptor binding	1
RNA polymerase II-specific DNA-binding transcription factor binding	1
chromosome	1
intracellular membrane-bounded organelle	1
nucleoplasm	1

Protein interactions and networks

STRING

3667 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
NCOR2	HDAC1	Q13547	996
NCOR2	HDAC3	O15379	995
NCOR2	BCL6	P41182	991
NCOR2	SIN3A	Q96ST3	990
NCOR2	RARA	P10276	987
NCOR2	NCOR1	O75376	985
NCOR2	TBL1X	O60907	984
NCOR2	TBL1Y	Q9BQ87	977
NCOR2	TBL1XR1	Q9BZK7	965
NCOR2	ATXN1	P54253	962
NCOR2	RBPJ	Q06330	959
NCOR2	ESR1	P03372	944
NCOR2	HDAC4	P56524	932
NCOR2	SPEN	Q96T58	931
NCOR2	GPS2	Q13227	924

IntAct

241 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:0914”(association)	0.900
HNRNPC	KPNA4	psi-mi:“MI:0915”(physical association)	0.830
RARA	NCOR1	psi-mi:“MI:0914”(association)	0.800
GPS2	NCOR2	psi-mi:“MI:0407”(direct interaction)	0.790
GPS2	NCOR2	psi-mi:“MI:0915”(physical association)	0.790
HDAC3	TBL1X	psi-mi:“MI:0914”(association)	0.760
KPNA4	NCOR2	psi-mi:“MI:0407”(direct interaction)	0.740

BioGRID (545): HMGA1 (Affinity Capture-Western), NCOR2 (Affinity Capture-Western), NCOR2 (Protein-peptide), PPARG (Reconstituted Complex), NCOR2 (Two-hybrid), PPARG (Reconstituted Complex), NCOR2 (Protein-peptide), NCOR2 (Affinity Capture-MS), KLF5 (Affinity Capture-Western), NCOR2 (Two-hybrid), NCOR2 (Affinity Capture-MS), NCOR2 (Affinity Capture-MS), NCOR2 (Affinity Capture-MS), NCOR2 (Affinity Capture-MS), NCOR2 (Affinity Capture-MS)

ESM2 similar proteins: A0A088MLT8, A2AQ25, B3KU38, B5DF41, E9PSK7, O15079, O35274, P0DPB3, P0DPB4, P12755, P49140, P85299, Q0D2I5, Q14DQ1, Q1LY51, Q3B7M3, Q3SYW5, Q4KMA0, Q4R3X1, Q50H33, Q5F3L9, Q5FVG6, Q5RD40, Q5XKK7, Q60698, Q6ZNC4, Q6ZUS6, Q6ZWB6, Q80U23, Q80U62, Q80XA6, Q812A5, Q86YI8, Q8BXL9, Q8K2W6, Q8ND83, Q8NFH8, Q8QFX1, Q8TEK3, Q924W7

Diamond homologs: A5PJX4, O75376, Q3U3N0, Q3UHF3, Q4KKX4, Q4R3R9, Q5REE1, Q5UAK0, Q5ZKT9, Q60974, Q7T105, Q7Z3K6, Q8N108, Q8N344, Q9WU42, Q9Y618, P25357, Q0GGX2, Q4R2Z8, Q55DP9, Q59E36, Q5FWT8, Q6NRZ0, Q6P116, Q8C796, Q8CFE3, Q8IZ40, Q8QG78, Q90WN5, Q9H0D2, Q9H4R4, Q9P2K3, Q9UKL0, Q9WUB5, Q10369, P34333, Q5ZJ40, Q6PGA0, Q6PJG2, Q8BXJ2

SIGNOR signaling

17 interactions.

A	Effect	B	Mechanism
NCOR2	down-regulates	AR	acetylation
NCOR2	down-regulates	PGR	acetylation
NCOR2	up-regulates	BHLHE41	binding
NCOR2	up-regulates	SPEN	binding
CHUK	down-regulates	NCOR2	phosphorylation
CAMK2A	down-regulates	NCOR2	phosphorylation
CAMK2G	down-regulates	NCOR2	phosphorylation
IKK-complex	down-regulates	NCOR2	phosphorylation
NCOR2	“up-regulates activity”	BCL6	binding
SIRT1	up-regulates	NCOR2
NCOR2	“down-regulates quantity by repression”	PPARG	“transcriptional regulation”
NR0B1	“up-regulates activity”	NCOR2	binding
CDK2	“down-regulates activity”	NCOR2	phosphorylation
NCOR2	up-regulates	SNW1	binding
SNW1	down-regulates	NCOR2	binding
FLT3	“down-regulates activity”	NCOR2	relocalization
RELA	“down-regulates activity”	NCOR2	relocalization

Enriched among interaction partners

Reactome pathways and GO biological processes over-represented among this gene’s 165 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
SUMOylation of intracellular receptors	7	19.3×	1e-05
Notch-HLH transcription pathway	5	16.7×	7e-04
Deactivation of the beta-catenin transactivating complex	8	15.3×	1e-05
NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux	6	15.2×	2e-04
Regulation of MECP2 expression and activity	5	15.1×	9e-04
Nuclear Receptor transcription pathway	9	14.8×	5e-06
NOTCH1 Intracellular Domain Regulates Transcription	6	11.7×	7e-04
Differentiation of naive CD4+ T cells to T helper 2 cells (Th2 cells)	9	10.8×	2e-05

GO biological processes:

GO term	Partners	Fold	FDR
positive regulation of miRNA transcription	9	16.7×	7e-07
cell fate commitment	8	15.1×	8e-06
mRNA transcription by RNA polymerase II	5	10.5×	4e-03
anatomical structure morphogenesis	11	9.8×	3e-06
cartilage development	6	9.6×	2e-03
inner ear morphogenesis	5	9.6×	6e-03
transcription by RNA polymerase II	19	8.5×	3e-10
vasculogenesis	5	8.1×	1e-02

Disease & clinical

Cancer significance

From intOGen — cancer-driver classification: loss-of-function (tumor-suppressor-like) across 8 cancer types — BRCA, COADREAD, ESCA, HCC, HGGNOS, LMS, PLMESO, PRAD.

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	1
Uncertain significance	462
Likely benign	81
Benign	44

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
800325	NM_006312.6(NCOR2):c.5909C>A (p.Ser1970Tyr)	Likely pathogenic

SpliceAI

9665 predictions. Top by Δscore:

Variant	Effect	Δscore
12:124326186:CCCA:C	donor_loss	1.0000
12:124326189:A:C	donor_loss	1.0000
12:124326367:CCAC:C	acceptor_gain	1.0000
12:124326368:CACC:C	acceptor_gain	1.0000
12:124326368:CACCT:C	acceptor_loss	1.0000
12:124326369:ACCTG:A	acceptor_loss	1.0000
12:124326370:CCT:C	acceptor_loss	1.0000
12:124326371:C:CA	acceptor_loss	1.0000
12:124326372:T:C	acceptor_loss	1.0000
12:124332314:CTTA:C	donor_loss	1.0000
12:124332315:TTA:T	donor_loss	1.0000
12:124332316:TACTG:T	donor_loss	1.0000
12:124332317:A:AC	donor_gain	1.0000
12:124332317:ACTGT:A	donor_loss	1.0000
12:124332318:C:CA	donor_gain	1.0000
12:124332318:CT:C	donor_gain	1.0000
12:124332318:CTG:C	donor_gain	1.0000
12:124332318:CTGT:C	donor_gain	1.0000
12:124332318:CTGTA:C	donor_gain	1.0000
12:124332332:ATT:A	donor_gain	1.0000
12:124332334:T:A	donor_gain	1.0000
12:124332463:TCCTG:T	acceptor_gain	1.0000
12:124332464:CCTGC:C	acceptor_gain	1.0000
12:124332465:CTG:C	acceptor_gain	1.0000
12:124332466:TG:T	acceptor_gain	1.0000
12:124332468:C:CC	acceptor_gain	1.0000
12:124333127:TACC:T	donor_loss	1.0000
12:124333129:C:CT	donor_loss	1.0000
12:124333277:GAC:G	acceptor_gain	1.0000
12:124333280:C:CA	acceptor_loss	1.0000

AlphaMissense

16286 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
12:124327552:A:G	L2347P	1.000
12:124327564:A:T	I2343N	1.000
12:124335139:A:T	I2136N	1.000
12:124341948:T:A	D1688V	1.000
12:124385767:A:G	L666S	1.000
12:124385779:A:G	L662P	1.000
12:124385779:A:T	L662H	1.000
12:124385793:C:A	K657N	1.000
12:124385793:C:G	K657N	1.000
12:124385795:T:C	K657E	1.000
12:124385799:G:C	N655K	1.000
12:124385799:G:T	N655K	1.000
12:124385802:G:C	F654L	1.000
12:124385802:G:T	F654L	1.000
12:124385803:A:G	F654S	1.000
12:124385804:A:G	F654L	1.000
12:124385807:A:C	Y653D	1.000
12:124385808:G:C	F652L	1.000
12:124385808:G:T	F652L	1.000
12:124385809:A:C	F652C	1.000
12:124385809:A:G	F652S	1.000
12:124385810:A:G	F652L	1.000
12:124385811:G:C	N651K	1.000
12:124385811:G:T	N651K	1.000
12:124385814:C:A	K650N	1.000
12:124385814:C:G	K650N	1.000
12:124385815:T:A	K650M	1.000
12:124385815:T:G	K650T	1.000
12:124385816:T:C	K650E	1.000
12:124385817:A:C	C649W	1.000

dbSNP variants (sampled 300 via entrez): RS1000004914 (12:124367112 A>C), RS1000007316 (12:124396787 C>T), RS1000014917 (12:124504715 C>T), RS1000023697 (12:124473080 G>A,T), RS1000028280 (12:124462921 T>C), RS1000035890 (12:124507377 A>C), RS1000036071 (12:124380695 G>A), RS1000046005 (12:124326530 T>G), RS1000048981 (12:124502541 G>A), RS1000053769 (12:124342913 T>C), RS1000056149 (12:124440619 C>G,T), RS1000059858 (12:124509905 G>A), RS1000066490 (12:124434485 T>C,G), RS1000075871 (12:124501667 T>C), RS1000090795 (12:124429487 C>A,T)

Disease associations

OMIM: gene MIM:600848 | disease phenotypes: MIM:254500

GenCC curated gene-disease

Mondo (1): plasma cell myeloma (MONDO:0009693)

Orphanet (2): Multiple myeloma (Orphanet:29073), AL amyloidosis (Orphanet:85443)

HPO phenotypes

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

GWAS associations

25 associations (top):

Study	Trait	p-value
GCST000477_54	Cognitive performance	7.000000e-06
GCST002005_3	Adverse response to chemotherapy (neutropenia/leucopenia) (all antimetabolite drugs)	9.000000e-06
GCST002142_14	Cocaine dependence	5.000000e-07
GCST002399_1	Clubfoot	2.000000e-07
GCST004863_64	Mosquito bite size	2.000000e-06
GCST005956_10	Waist-to-hip ratio adjusted for BMI	6.000000e-08
GCST005958_11	Waist-to-hip ratio adjusted for BMI (age >50)	4.000000e-07
GCST005962_22	Waist-to-hip ratio adjusted for BMI x sex x age interaction (4df test)	1.000000e-08
GCST006481_19	Lung function (FEV1)	5.000000e-08
GCST006630_38	Diastolic blood pressure	1.000000e-17
GCST008839_306	Height	4.000000e-12
GCST009597_35	Multiple sclerosis	2.000000e-07
GCST010242_35	HDL cholesterol levels	1.000000e-15
GCST012227_578	Hip circumference adjusted for BMI	1.000000e-10
GCST012227_579	Hip circumference adjusted for BMI	4.000000e-08
GCST90000025_1009	Appendicular lean mass	3.000000e-40
GCST90000026_40	Appendicular lean mass	4.000000e-20
GCST90000027_20	Appendicular lean mass	8.000000e-24
GCST90002393_280	Monocyte count	6.000000e-10
GCST90002397_224	Mean spheric corpuscular volume	3.000000e-11
GCST90002401_52	Platelet distribution width	2.000000e-10
GCST90020028_1169	Hip circumference adjusted for BMI	5.000000e-12
GCST90020028_1170	Hip circumference adjusted for BMI	5.000000e-12
GCST90020028_1171	Hip circumference adjusted for BMI	6.000000e-09
GCST90020028_1172	Hip circumference adjusted for BMI	5.000000e-08

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0003926	neuropsychological test
EFO:0008378	mosquito bite reaction size measurement
EFO:0007788	BMI-adjusted waist-hip ratio
EFO:0008007	age at assessment
EFO:0008343	sex interaction measurement
EFO:0004314	forced expiratory volume
EFO:0006336	diastolic blood pressure
EFO:0004612	high density lipoprotein cholesterol measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0004980	appendicular lean mass
EFO:0005091	monocyte count
EFO:0007984	platelet component distribution width

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D009101	Multiple Myeloma	C04.557.595.500; C14.907.454.460; C15.378.147.780.650; C15.378.463.515.460; C20.683.515.845; C20.683.780.650

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (6): CHEMBL2096976 (PROTEIN-PROTEIN INTERACTION), CHEMBL2111363 (PROTEIN COMPLEX), CHEMBL3885590 (PROTEIN COMPLEX), CHEMBL3885591 (PROTEIN COMPLEX), CHEMBL4523673 (PROTEIN-PROTEIN INTERACTION), CHEMBL5949 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

15 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 134,527 (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
CHEMBL388590	BENZBROMARONE	4	8,245
CHEMBL1213492	GIVINOSTAT	4	2,827
CHEMBL343448	ROMIDEPSIN	4	12,963
CHEMBL483254	PANOBINOSTAT	4	11,666
CHEMBL98	VORINOSTAT	4	50,361
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
CHEMBL2105763	QUISINOSTAT	2	1,843
CHEMBL2364628	RICOLINOSTAT	2	2,028
CHEMBL272980	MOCETINOSTAT	2	3,884
CHEMBL3622533	FIMEPINOSTAT	2	2,487
CHEMBL99	TRICHOSTATIN	1	22,314

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

Binding affinities (BindingDB)

178 measured of 233 human assays (262 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEBI:46024	IC50	4.9 nM
6-bromanyl-2-(furan-2-yl)quinoline-4-carboxylic acid	IC50	23 nM
N-hydroxy-4-[(3-oxo-[1,2]thiazolo[5,4-b]pyridin-2-yl)methyl]benzamide	IC50	175 nM	US-10011611: Histone deacetylase inhibitors and methods for use thereof
7-(4-methoxyphenyl)-5-phenyl-pyrido[2,3-d]pyrimidin-4-amine	IC50	237 nM
7-(4-fluorophenyl)-5-(4-methylphenyl)-4-pyrido[2,3-d]pyrimidinamine	IC50	336 nM
6-bromo-2-thiophen-2-ylquinoline-4-carboxylic acid	IC50	395 nM
5-(3a-hydroxy-2-oxo-3,4,6,6a-tetrahydro-1H-thieno[3,4-d]imidazol-4-yl)pentanoic acid methyl ester	IC50	577 nM
4-(4-butoxyphenyl)-5-cyano-2-methyl-N-phenyl-6-sulfanylidene-1H-pyridine-3-carboxamide	IC50	778 nM
1-[2-(N-methylsulfonyl-4-phenoxyanilino)-1-oxoethyl]-4-piperidinecarboxamide	IC50	792 nM
MLS000548752	EC50	907 nM
4-(3-bromophenyl)-2-(4-bromophenyl)-7-methyl-2H-pyrazolo[3,4-d]pyridazine	IC50	915 nM
MLS001173402	IC50	934 nM
SMR000620955	IC50	941 nM
SMR000306271	IC50	1090 nM
2-(4-benzofuro[3,2-d]pyrimidinylthio)-N-[2-(trifluoromethyl)phenyl]acetamide	IC50	1110 nM
3-(1-benzofuran-2-ylcarbonyl)-2-(3-chlorophenyl)-1-(5-methyl-1,2-oxazol-3-yl)-4-oxidanyl-2H-pyrrol-5-one	IC50	1190 nM
cid_3245690	IC50	1230 nM
SMR000516584	IC50	1270 nM
d-Desthiobiotin	IC50	1380 nM
MLS000690352	IC50	1390 nM
1-[2-(4-methoxyphenyl)-3,4-dimethylpyrazolo[3,4-d]pyridazin-7-yl]-N-[(2-methylphenyl)methyl]piperidine-4-carboxamide	IC50	1440 nM
2-[2,4-bis(chloranyl)phenoxy]-N-[4-(6-morpholin-4-ylpyridazin-3-yl)phenyl]ethanamide	IC50	1500 nM
MLS000585653	IC50	1560 nM
6-bromo-2-(2-furyl)-4-quinolinecarboxylic acid	IC50	1580 nM
N-(4,6-dimethyl-2-pyridinyl)-N’-(3-methoxyphenyl)thiourea	IC50	1610 nM
1,3,6-Trimethyl-1H-pyrimido[5,4-e][1,2,4]triazine-5,7-dione	EC50	1610 nM
SMR000079256	IC50	1670 nM
4-hydroxy-3-[(7-methoxy-2-benzofuranyl)-oxomethyl]-1-(5-methyl-3-isoxazolyl)-2-thiophen-2-yl-2H-pyrrol-5-one	IC50	1730 nM
2-(1,3-benzodioxol-5-yl)-6-bromoquinoline-4-carboxylic acid	IC50	1760 nM
6-chloro-N-[3-([1,3]thiazolo[5,4-b]pyridin-2-yl)phenyl]pyridine-3-carboxamide	IC50	1800 nM
3-(1-benzofuran-2-carbonyl)-2-(4-chlorophenyl)-4-hydroxy-1-(5-methyl-1,2-oxazol-3-yl)-2H-pyrrol-5-one	IC50	1840 nM
cid_3240852	IC50	1920 nM
N-Benzhydryl-2-(8,8-dimethyl-1-oxo-8,9-dihydro-1H,6H-7-oxa-11-thia-2,4,10-triaza-benzo[b]fluoren-2-yl )-acetamide	IC50	1940 nM
3-(1-benzofuran-2-ylcarbonyl)-2-(3-bromophenyl)-1-(5-methyl-1,2-oxazol-3-yl)-4-oxidanyl-2H-pyrrol-5-one	IC50	1970 nM
MLS000050497	IC50	2000 nM
2-(8-chloro-4-oxo-2-sulfanylidene-1H-benzofuro[3,2-d]pyrimidin-3-yl)acetic acid ethyl ester	IC50	2020 nM
MLS000548751	IC50	2070 nM
cid_2946893	IC50	2140 nM
N-(4-methoxyphenyl)-2-[(4-phenyl-5-thiophen-2-yl-1,2,4-triazol-3-yl)sulfanyl]acetamide	IC50	2160 nM
SMR000322789	IC50	2220 nM
3-[2-benzofuranyl(oxo)methyl]-2-(3-bromophenyl)-1-[2-(dimethylamino)ethyl]-4-hydroxy-2H-pyrrol-5-one	IC50	2250 nM
SMR000414964	IC50	2300 nM
1-(6-bromo-4-phenylquinazolin-2-yl)piperidine-4-carboxylic acid	IC50	2320 nM
3-(1-benzofuran-2-carbonyl)-2-(3-bromophenyl)-4-hydroxy-1-(2-morpholin-4-ylethyl)-2H-pyrrol-5-one	IC50	2360 nM
6,8-dibromo-4-(1-piperidinyl)quinazoline	IC50	2360 nM
SMR000550011	IC50	2380 nM
SMR000646795	IC50	2390 nM
4-(5-methyl-2-furanyl)-2-sulfanylidene-5,6,7,8-tetrahydro-1H-quinoline-3-carbonitrile	IC50	2400 nM
cid_2505717	IC50	2430 nM
SMR000269454	IC50	2480 nM

ChEMBL bioactivities

892 potent at pChembl≥5 of 951 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.76	IC50	0.1726	nM	CHEMBL4444219
9.59	IC50	0.2553	nM	CHEMBL4444219
9.59	Ki	0.26	nM	TRICHOSTATIN
9.55	IC50	0.28	nM	CHEMBL4444219
9.50	IC50	0.316	nM	CHEMBL4444219
9.42	IC50	0.38	nM	CHEMBL5083249
9.37	IC50	0.43	nM	CHEMBL5078985
9.28	Kd	0.53	nM	CHEMBL5282647
9.27	IC50	0.5341	nM	CHEMBL4444219
9.26	IC50	0.55	nM	CHEMBL5087431
9.18	IC50	0.66	nM	CHEMBL4744689
9.15	IC50	0.7	nM	CHEMBL3593247
9.15	Kd	0.7	nM	CHEMBL5814333
9.14	IC50	0.72	nM	CHEMBL5532146
9.11	Kd	0.77	nM	CHEMBL5834831
9.09	Kd	0.81	nM	CHEMBL5802828
9.08	Ki	0.84	nM	TRICHOSTATIN
9.06	Kd	0.87	nM	CHEMBL5923367
9.02	Kd	0.96	nM	CHEMBL5849108
9.02	Kd	0.96	nM	CHEMBL5978380
9.00	IC50	1	nM	CHEMBL3970532
8.97	IC50	1.08	nM	CHEMBL5565699
8.96	IC50	1.1	nM	CHEMBL4291290
8.96	IC50	1.1	nM	CHEMBL4749655
8.88	Kd	1.33	nM	CHEMBL5848081
8.87	Kd	1.36	nM	CHEMBL5876992
8.85	IC50	1.41	nM	CHEMBL4063938
8.85	Kd	1.42	nM	CHEMBL5838489
8.82	Ki	1.5	nM	APICIDIN
8.82	Kd	1.5	nM	CHEMBL5904511
8.81	Kd	1.55	nM	CHEMBL6047968
8.79	Kd	1.61	nM	CHEMBL5834405
8.78	IC50	1.673	nM	PANOBINOSTAT
8.75	Kd	1.79	nM	CHEMBL5803625
8.74	IC50	1.8	nM	FIMEPINOSTAT
8.74	IC50	1.82	nM	CHEMBL5561465
8.74	IC50	1.82	nM	CHEMBL5561596
8.71	IC50	1.926	nM	PANOBINOSTAT
8.70	IC50	2	nM	CHEMBL3098602
8.70	Ki	2	nM	VORINOSTAT
8.70	Kd	2	nM	CHEMBL255686
8.70	IC50	2	nM	CHEMBL4785064
8.70	IC50	1.98	nM	CHEMBL5555272
8.70	IC50	2.01	nM	CHEMBL5556752
8.69	IC50	2.059	nM	PANOBINOSTAT
8.69	Kd	2.03	nM	CHEMBL6037729
8.68	IC50	2.097	nM	PANOBINOSTAT
8.68	IC50	2.1	nM	PANOBINOSTAT
8.68	IC50	2.1	nM	QUISINOSTAT HYDROCHLORIDE
8.67	Kd	2.14	nM	CHEMBL6038920

PubChem BioAssay actives

610 with measured affinity, of 1268 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
(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
(2E,4E,6R)-7-[4-(dimethylamino)phenyl]-N-hydroxy-4,6-dimethyl-7-oxohepta-2,4-dienamide	331899: Displacement of fluorescent 5-(3-(3-(4-((4-((7-(hydroxyamino)-7-oxoheptyl)carbamoyl)phenylamino)methyl)-1H-1,2,3-triazol-1-yl)propyl)thioureido)-2-(3-hydroxy-6-oxo-6H-xanthen-9-yl)benzoic acid from human HDAC3/NcoR2 by fluorescence polarization assay	ki	0.0003	uM
N-[[4-(propylaminocarbamoyl)phenyl]methyl]-1H-indole-2-carboxamide	2067517: Inhibition of C-terminal His-tagged human HDAC3 (1 to 428 residues)/N-terminal GST tagged human NCOR2 (395 to 489 residues) expressed in baculovirus-infected Sf9 cells using Boc-Lys-(acetyl)-AMC as substrate preincubated with enzyme for 1 hr followed by substrate addition and measured after 2 hrs by fluorescence analysis	ic50	0.0004	uM
N-[[4-(propylaminocarbamoyl)phenyl]methyl]-1-benzofuran-2-carboxamide	2067517: Inhibition of C-terminal His-tagged human HDAC3 (1 to 428 residues)/N-terminal GST tagged human NCOR2 (395 to 489 residues) expressed in baculovirus-infected Sf9 cells using Boc-Lys-(acetyl)-AMC as substrate preincubated with enzyme for 1 hr followed by substrate addition and measured after 2 hrs by fluorescence analysis	ic50	0.0004	uM
N-[[4-(propylaminocarbamoyl)phenyl]methyl]-1-benzothiophene-2-carboxamide	2067517: Inhibition of C-terminal His-tagged human HDAC3 (1 to 428 residues)/N-terminal GST tagged human NCOR2 (395 to 489 residues) expressed in baculovirus-infected Sf9 cells using Boc-Lys-(acetyl)-AMC as substrate preincubated with enzyme for 1 hr followed by substrate addition and measured after 2 hrs by fluorescence analysis	ic50	0.0006	uM
7-[2-(2-aminopyrimidin-5-yl)-4-morpholin-4-ylpyrrolo[2,3-d]pyrimidin-7-yl]-N-hydroxyheptanamide	1702062: Inhibition of recombinant human C-terminal His-tagged HDAC3 (1 to 428 end residues)/N-terminal GST-tagged recombinant human NCoR2 (395 to 489 residues) expressed in baculovirus infected Sf9 cells using fluorogenic HDAC substrate 3 measured after 30 mins by fluorescence based assay	ic50	0.0007	uM
N-[[4-(propylaminocarbamoyl)phenyl]methyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxamide	2067517: Inhibition of C-terminal His-tagged human HDAC3 (1 to 428 residues)/N-terminal GST tagged human NCOR2 (395 to 489 residues) expressed in baculovirus-infected Sf9 cells using Boc-Lys-(acetyl)-AMC as substrate preincubated with enzyme for 1 hr followed by substrate addition and measured after 2 hrs by fluorescence analysis	ic50	0.0007	uM
(5R,8S,11S)-5-methyl-8-propan-2-yl-11-[(E)-4-sulfanylbut-1-enyl]-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	1466454: Inhibition of full length human C-terminal His-tagged HDAC3/N-terminal GST-tagged NCOR2 (395 to 489 residues) expressed in baculovirus infected Sf9 insect cells using BPS HDAC substrate 3 after 30 mins by fluorescence assay	ic50	0.0007	uM
N-[6-(2-aminoanilino)-6-oxohexyl]-4-methylbenzamide	1972765: Inhibition of human HDAC3/NCOR2 using Acetyl-Lys(Ac)-AMC as substrate measured after 1 hrs by fluorescence release assay	ic50	0.0010	uM
N-hydroxy-7-[2-[3-(hydroxymethyl)phenyl]-6-morpholin-4-ylpurin-9-yl]heptanamide	1702062: Inhibition of recombinant human C-terminal His-tagged HDAC3 (1 to 428 end residues)/N-terminal GST-tagged recombinant human NCoR2 (395 to 489 residues) expressed in baculovirus infected Sf9 cells using fluorogenic HDAC substrate 3 measured after 30 mins by fluorescence based assay	ic50	0.0011	uM
[(1S,4E)-cyclooct-4-en-1-yl] N-[4-[(5R,8S,11S)-5-methyl-6,9,13-trioxo-11-[(E)-4-sulfanylbut-1-enyl]-10-oxa-3,17-dithia-7,14,19,20-tetrazatricyclo[14.2.1.12,5]icosa-1(18),2(20),16(19)-trien-8-yl]butyl]carbamate	1415587: Inhibition of C-terminal His-tagged full length recombinant human HDAC3/N-terminal GST-tagged NCOR2 (395 to 489 residues) expressed in baculovirus infected Sf9 insect cells using HDAC substrate 3 after 30 mins by fluorescence assay	ic50	0.0011	uM
N-[4-(propylaminocarbamoyl)phenyl]-8-(4-pyridin-3-yltriazol-1-yl)octanamide	2067517: Inhibition of C-terminal His-tagged human HDAC3 (1 to 428 residues)/N-terminal GST tagged human NCOR2 (395 to 489 residues) expressed in baculovirus-infected Sf9 cells using Boc-Lys-(acetyl)-AMC as substrate preincubated with enzyme for 1 hr followed by substrate addition and measured after 2 hrs by fluorescence analysis	ic50	0.0011	uM
N-[(2S)-3-(1H-indol-3-yl)-1-oxo-1-[4-(propylaminocarbamoyl)anilino]propan-2-yl]-4-methoxybenzamide	1469141: Inhibition of full length recombinant human C-terminal His-tagged HDAC3/N-terminal GST-tagged NCOR2 co-expressed in baculovirus expression system using Boc-Lys(acetyl)-AMC as substrate preincubated for 1 hr followed by substrate addition measured after 2 hrs by fluorescence assay	ic50	0.0014	uM
(3S,6S,9S,12R)-3-[(2S)-butan-2-yl]-6-[(1-methoxyindol-3-yl)methyl]-9-(6-oxooctyl)-1,4,7,10-tetrazabicyclo[10.4.0]hexadecane-2,5,8,11-tetrone	331899: Displacement of fluorescent 5-(3-(3-(4-((4-((7-(hydroxyamino)-7-oxoheptyl)carbamoyl)phenylamino)methyl)-1H-1,2,3-triazol-1-yl)propyl)thioureido)-2-(3-hydroxy-6-oxo-6H-xanthen-9-yl)benzoic acid from human HDAC3/NcoR2 by fluorescence polarization assay	ki	0.0015	uM
Panobinostat	1548758: 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 30 mins followed by substrate addition and measured after 2 hrs by fluorescence based microplate reader analysis	ic50	0.0017	uM
N-[[4-(propylaminocarbamoyl)phenyl]methyl]furo[3,2-c]pyridine-2-carboxamide	2067517: Inhibition of C-terminal His-tagged human HDAC3 (1 to 428 residues)/N-terminal GST tagged human NCOR2 (395 to 489 residues) expressed in baculovirus-infected Sf9 cells using Boc-Lys-(acetyl)-AMC as substrate preincubated with enzyme for 1 hr followed by substrate addition and measured after 2 hrs by fluorescence analysis	ic50	0.0018	uM
(E)-N-[[4-(propylaminocarbamoyl)phenyl]methyl]-3-pyridin-2-ylprop-2-enamide	2067517: Inhibition of C-terminal His-tagged human HDAC3 (1 to 428 residues)/N-terminal GST tagged human NCOR2 (395 to 489 residues) expressed in baculovirus-infected Sf9 cells using Boc-Lys-(acetyl)-AMC as substrate preincubated with enzyme for 1 hr followed by substrate addition and measured after 2 hrs by fluorescence analysis	ic50	0.0018	uM
N-hydroxy-2-[[2-(6-methoxy-3-pyridinyl)-4-morpholin-4-ylthieno[3,2-d]pyrimidin-6-yl]methyl-methylamino]pyrimidine-5-carboxamide	1312853: Inhibition of full length C-terminal His-tagged human recombinant HDAC3/NCOR2 (395 to 489 residues) expressed in baculovirus infected insect Sf9 cells using Ac-peptide-AMC as substrate assessed as release of AMC preincubated for 15 mins followed by substrate addition measured after 1 hr by fluorescence assay	ic50	0.0018	uM
7-[2-(6-amino-3-pyridinyl)-6-morpholin-4-ylpurin-9-yl]-N-hydroxyheptanamide	1702062: Inhibition of recombinant human C-terminal His-tagged HDAC3 (1 to 428 end residues)/N-terminal GST-tagged recombinant human NCoR2 (395 to 489 residues) expressed in baculovirus infected Sf9 cells using fluorogenic HDAC substrate 3 measured after 30 mins by fluorescence based assay	ic50	0.0020	uM
N-[[4-(propylaminocarbamoyl)phenyl]methyl]thieno[3,2-c]pyridine-2-carboxamide	2067517: Inhibition of C-terminal His-tagged human HDAC3 (1 to 428 residues)/N-terminal GST tagged human NCOR2 (395 to 489 residues) expressed in baculovirus-infected Sf9 cells using Boc-Lys-(acetyl)-AMC as substrate preincubated with enzyme for 1 hr followed by substrate addition and measured after 2 hrs by fluorescence analysis	ic50	0.0020	uM
N-[[4-(propylaminocarbamoyl)phenyl]methyl]-8-[[(E)-3-pyridin-3-ylprop-2-enoyl]amino]octanamide	2067517: Inhibition of C-terminal His-tagged human HDAC3 (1 to 428 residues)/N-terminal GST tagged human NCOR2 (395 to 489 residues) expressed in baculovirus-infected Sf9 cells using Boc-Lys-(acetyl)-AMC as substrate preincubated with enzyme for 1 hr followed by substrate addition and measured after 2 hrs by fluorescence analysis	ic50	0.0020	uM
5-[3-[4-[[4-[[7-(hydroxyamino)-7-oxoheptyl]carbamoyl]anilino]methyl]triazol-1-yl]propylcarbamothioylamino]-2-(3-oxoxanthen-9-yl)benzoic acid	331899: Displacement of fluorescent 5-(3-(3-(4-((4-((7-(hydroxyamino)-7-oxoheptyl)carbamoyl)phenylamino)methyl)-1H-1,2,3-triazol-1-yl)propyl)thioureido)-2-(3-hydroxy-6-oxo-6H-xanthen-9-yl)benzoic acid from human HDAC3/NcoR2 by fluorescence polarization assay	kd	0.0020	uM
Vorinostat	331899: Displacement of fluorescent 5-(3-(3-(4-((4-((7-(hydroxyamino)-7-oxoheptyl)carbamoyl)phenylamino)methyl)-1H-1,2,3-triazol-1-yl)propyl)thioureido)-2-(3-hydroxy-6-oxo-6H-xanthen-9-yl)benzoic acid from human HDAC3/NcoR2 by fluorescence polarization assay	ki	0.0020	uM
(2S)-N’-hydroxy-2-[[(2R)-5-oxopyrrolidine-2-carbonyl]amino]-N-[3-(trifluoromethyl)phenyl]octanediamide	1061953: Inhibition of human HDAC3/NCOR2 using RHKK(Ac) as substrate by fluorimetric analysis	ic50	0.0020	uM
N-hydroxy-2-[4-[[(1-methylindol-3-yl)methylamino]methyl]piperidin-1-yl]pyrimidine-5-carboxamide;hydrochloride	1708888: Inhibition of human C-terminal His-tagged HDAC3/N-terminal GST-tagged NCOR2 expressed in baculovirus infected Sf9 cells using Ac-peptide as substrate preincubated for 15 mins followed by substrate and trypsin addition and further incubated for 60 mins	ic50	0.0021	uM
N-[[4-(propylaminocarbamoyl)phenyl]methyl]-1H-pyrrolo[2,3-c]pyridine-2-carboxamide	2067517: Inhibition of C-terminal His-tagged human HDAC3 (1 to 428 residues)/N-terminal GST tagged human NCOR2 (395 to 489 residues) expressed in baculovirus-infected Sf9 cells using Boc-Lys-(acetyl)-AMC as substrate preincubated with enzyme for 1 hr followed by substrate addition and measured after 2 hrs by fluorescence analysis	ic50	0.0024	uM
N-hydroxy-2-[[2-(4-methoxyphenyl)-9-methyl-6-morpholin-4-ylpurin-8-yl]methyl-methylamino]pyrimidine-5-carboxamide	1312853: Inhibition of full length C-terminal His-tagged human recombinant HDAC3/NCOR2 (395 to 489 residues) expressed in baculovirus infected insect Sf9 cells using Ac-peptide-AMC as substrate assessed as release of AMC preincubated for 15 mins followed by substrate addition measured after 1 hr by fluorescence assay	ic50	0.0026	uM
N-hydroxy-2-[methyl-[(9-methyl-6-morpholin-4-yl-2-pyridin-4-ylpurin-8-yl)methyl]amino]pyrimidine-5-carboxamide	1312853: Inhibition of full length C-terminal His-tagged human recombinant HDAC3/NCOR2 (395 to 489 residues) expressed in baculovirus infected insect Sf9 cells using Ac-peptide-AMC as substrate assessed as release of AMC preincubated for 15 mins followed by substrate addition measured after 1 hr by fluorescence assay	ic50	0.0027	uM
(E)-N-[[4-(propylaminocarbamoyl)phenyl]methyl]-3-pyridin-4-ylprop-2-enamide	2067517: Inhibition of C-terminal His-tagged human HDAC3 (1 to 428 residues)/N-terminal GST tagged human NCOR2 (395 to 489 residues) expressed in baculovirus-infected Sf9 cells using Boc-Lys-(acetyl)-AMC as substrate preincubated with enzyme for 1 hr followed by substrate addition and measured after 2 hrs by fluorescence analysis	ic50	0.0027	uM
N-[(2S)-1-(1H-indol-3-yl)-3-[4-[(E)-3-oxo-3-(2-propylhydrazinyl)prop-1-enyl]phenoxy]propan-2-yl]-4-methoxybenzamide	1469141: Inhibition of full length recombinant human C-terminal His-tagged HDAC3/N-terminal GST-tagged NCOR2 co-expressed in baculovirus expression system using Boc-Lys(acetyl)-AMC as substrate preincubated for 1 hr followed by substrate addition measured after 2 hrs by fluorescence assay	ic50	0.0028	uM
N-hydroxy-2-[methyl-[[3-[1-[(4-methylphenyl)methyl]piperidin-4-yl]-1,2,4-oxadiazol-5-yl]methyl]amino]pyrimidine-5-carboxamide	1566804: Inhibition of human recombinant full length C-terminal His-tagged HDAC3 (1 to 428 residues)/N-terminal GST-tagged NCOR2 (395 to 489 residues) expressed in Sf9 cells using Ac-peptide-AMC as substrate after 1 hr by fluorescence assay	ic50	0.0030	uM
N-hydroxy-2-[2-(1H-indol-3-ylmethyl)-2,8-diazaspiro[4.5]decan-8-yl]pyrimidine-5-carboxamide;hydrochloride	1708888: Inhibition of human C-terminal His-tagged HDAC3/N-terminal GST-tagged NCOR2 expressed in baculovirus infected Sf9 cells using Ac-peptide as substrate preincubated for 15 mins followed by substrate and trypsin addition and further incubated for 60 mins	ic50	0.0030	uM
N-[7-oxo-7-(2-propylhydrazinyl)heptyl]-1H-pyrrolo[3,2-c]pyridine-2-carboxamide	2067517: Inhibition of C-terminal His-tagged human HDAC3 (1 to 428 residues)/N-terminal GST tagged human NCOR2 (395 to 489 residues) expressed in baculovirus-infected Sf9 cells using Boc-Lys-(acetyl)-AMC as substrate preincubated with enzyme for 1 hr followed by substrate addition and measured after 2 hrs by fluorescence analysis	ic50	0.0030	uM
Romidepsin	673992: Inhibition of recombinant HDAC3/NCoR2 using Ac-Lys(Ac)-AMC as substrate after 30 mins by fluorescence analysis	ic50	0.0030	uM
(E)-N-[[4-(propylaminocarbamoyl)phenyl]methyl]-3-pyridin-3-ylprop-2-enamide	2067517: Inhibition of C-terminal His-tagged human HDAC3 (1 to 428 residues)/N-terminal GST tagged human NCOR2 (395 to 489 residues) expressed in baculovirus-infected Sf9 cells using Boc-Lys-(acetyl)-AMC as substrate preincubated with enzyme for 1 hr followed by substrate addition and measured after 2 hrs by fluorescence analysis	ic50	0.0031	uM
N’-hydroxy-N-[(E)-(4-prop-2-ynoxyphenyl)methylideneamino]octanediamide	594123: Inhibition of full length HDAC3/NCoR2 assessed as 7-amino-4-methylcoumarin release from fluorophore conjugated substrate after 5 mins by fluorescence assay	ic50	0.0031	uM
(5R,8S,11S)-11-[(Z)-2-fluoro-4-sulfanylbut-1-enyl]-5-methyl-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	1566039: Inhibition of human recombinant full length C-terminal His-tagged HDAC3 (1 to 428 residues)/N-terminal GST-tagged NCOR2 (395 to 489 residues) expressed in baculovirus infected Sf9 cells using Ac-peptide-AMC as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluorescence based assay	ic50	0.0032	uM
2-[[2-(2-aminopyrimidin-5-yl)-9-methyl-6-morpholin-4-ylpurin-8-yl]methyl-methylamino]-N-hydroxypyrimidine-5-carboxamide	1312853: Inhibition of full length C-terminal His-tagged human recombinant HDAC3/NCOR2 (395 to 489 residues) expressed in baculovirus infected insect Sf9 cells using Ac-peptide-AMC as substrate assessed as release of AMC preincubated for 15 mins followed by substrate addition measured after 1 hr by fluorescence assay	ic50	0.0033	uM
2-[[2-(4-aminophenyl)-9-methyl-6-morpholin-4-ylpurin-8-yl]methyl-methylamino]-N-hydroxypyrimidine-5-carboxamide	1312853: Inhibition of full length C-terminal His-tagged human recombinant HDAC3/NCOR2 (395 to 489 residues) expressed in baculovirus infected insect Sf9 cells using Ac-peptide-AMC as substrate assessed as release of AMC preincubated for 15 mins followed by substrate addition measured after 1 hr by fluorescence assay	ic50	0.0034	uM
(2S,6R,9S,12R,13S)-12-[(2S)-butan-2-yl]-13-hydroxy-6-(2-methylsulfanylethyl)-2-[(E)-4-sulfanylbut-1-enyl]-9-(sulfanylmethyl)-1-oxa-5,8,11-triazacyclopentadecane-4,7,10,15-tetrone	620938: Inhibition of recombinant human HDAC2/NCOR2 using Boc-L-Lys(epsilon-acetyl)-AMC as substrate by two-step fluorogenic assay	ic50	0.0035	uM
N-hydroxy-7-[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)pyrazol-1-yl]heptanamide	1476139: Inhibition of human recombinant HDAC3 (1 to 428 residues)/N-terminal GST-tagged NCOR2 (395 to 489 residues) expressed in Baculovirus infected insect cells in presence of ATP	ic50	0.0039	uM
(3S,6Z,9S,12R,16S)-6-ethylidene-3,12-di(propan-2-yl)-16-[(E)-4-sulfanylbut-1-enyl]-9-(sulfanylmethyl)-1-oxa-4,7,10,13-tetrazacyclohexadecane-2,5,8,11,14-pentone	620938: Inhibition of recombinant human HDAC2/NCOR2 using Boc-L-Lys(epsilon-acetyl)-AMC as substrate by two-step fluorogenic assay	ic50	0.0039	uM
(2S)-10-[[5-chloro-2-[(1S,5R)-7-hydroxy-3-oxa-9-azabicyclo[3.3.1]nonan-9-yl]pyrimidin-4-yl]amino]-2-cyclopropyl-3,3-difluoro-7-methyl-2,4-dihydro-1H-[1,4]oxazepino[2,3-c]quinolin-6-one	1987510: Inhibition of C-terminal NanoLuc-fused BCL6 (unknown origin)/Halo-tagged SMRT (unknown origin) interaction transfected in HEK293T cells measured after 6 hrs by NanoBRET assay	ic50	0.0045	uM
N-hydroxy-2-[[2-(6-methoxy-3-pyridinyl)-9-methyl-6-morpholin-4-ylpurin-8-yl]methyl-methylamino]pyrimidine-5-carboxamide	1312853: Inhibition of full length C-terminal His-tagged human recombinant HDAC3/NCOR2 (395 to 489 residues) expressed in baculovirus infected insect Sf9 cells using Ac-peptide-AMC as substrate assessed as release of AMC preincubated for 15 mins followed by substrate addition measured after 1 hr by fluorescence assay	ic50	0.0046	uM
N-hydroxy-2-[4-[[(1-methylindol-3-yl)methylamino]methyl]piperidin-1-yl]pyrimidine-5-carboxamide	1321710: Inhibition of full length recombinant human HDAC3/NCOR2 expressed in baculovirus infected Sf9 cells using RHKK-Ac as substrate by fluorescence analysis	ic50	0.0049	uM
7-[5-(3,5-dimethyl-1,2-oxazol-4-yl)-3-[(4-fluorophenyl)methyl]indol-1-yl]-N-hydroxyheptanamide	1545788: 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(Ac)-AMC as substrate preincubated for 15 mins followed by substrate addition and measured after 60 mins by fluorometric method	ic50	0.0050	uM
N-hydroxy-2-[4-[[[6-methoxy-2-(5-methylfuran-2-yl)-7-(3-pyrrolidin-1-ylpropoxy)quinolin-4-yl]amino]methyl]piperidin-1-yl]pyrimidine-5-carboxamide	1775565: Inhibition of full length human C-terminal His-tagged HDAC3/human N-terminal GST-agged NCOR2 using fluorogenic acetylated peptide as substrate incubated for 30 mins by fluorescence plate reader assay	ic50	0.0050	uM
N-[(2S)-3-(1H-indol-3-yl)-1-oxo-1-[[7-oxo-7-(2-propylhydrazinyl)heptyl]amino]propan-2-yl]-4-methoxybenzamide	1469141: Inhibition of full length recombinant human C-terminal His-tagged HDAC3/N-terminal GST-tagged NCOR2 co-expressed in baculovirus expression system using Boc-Lys(acetyl)-AMC as substrate preincubated for 1 hr followed by substrate addition measured after 2 hrs by fluorescence assay	ic50	0.0052	uM
N’-propyl-8-(4-pyridin-3-yltriazol-1-yl)octanehydrazide	2067517: Inhibition of C-terminal His-tagged human HDAC3 (1 to 428 residues)/N-terminal GST tagged human NCOR2 (395 to 489 residues) expressed in baculovirus-infected Sf9 cells using Boc-Lys-(acetyl)-AMC as substrate preincubated with enzyme for 1 hr followed by substrate addition and measured after 2 hrs by fluorescence analysis	ic50	0.0054	uM
N-[(2S)-3-(1H-indol-3-yl)-1-oxo-1-[[4-(propylaminocarbamoyl)phenyl]methylamino]propan-2-yl]-4-methoxybenzamide	1469141: Inhibition of full length recombinant human C-terminal His-tagged HDAC3/N-terminal GST-tagged NCOR2 co-expressed in baculovirus expression system using Boc-Lys(acetyl)-AMC as substrate preincubated for 1 hr followed by substrate addition measured after 2 hrs by fluorescence assay	ic50	0.0056	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Estradiol	affects binding, increases reaction, decreases expression, decreases reaction, affects cotreatment (+1 more)	7
Rifampin	increases reaction, affects binding, decreases reaction, increases expression, decreases activity (+1 more)	6
bisphenol A	affects folding, increases methylation, decreases activity, decreases methylation, affects binding (+3 more)	5
sodium arsenite	increases expression, increases methylation, affects cotreatment, decreases expression, increases abundance	4
Calcitriol	decreases reaction, increases reaction, affects cotreatment, increases activity, increases expression (+1 more)	4
Tamoxifen	decreases reaction, increases activity, increases expression, decreases expression, affects binding (+2 more)	4
methylmercuric chloride	increases expression, affects cotreatment	3
Fulvestrant	increases expression, affects cotreatment, increases methylation, decreases expression, affects binding (+2 more)	3
arsenite	decreases reaction, increases expression, affects binding, decreases expression	2
U 0126	decreases expression, affects binding, decreases reaction, increases reaction, decreases activity (+1 more)	2
lithocholic acid acetate	decreases reaction, affects cotreatment, increases activity, increases expression, affects binding (+1 more)	2
bisphenol S	affects binding, decreases reaction, affects cotreatment, decreases expression	2
bisphenol AF	affects binding, affects folding, increases reaction, decreases reaction	2
Acetaminophen	increases expression, decreases expression	2
Air Pollutants	affects cotreatment, decreases expression, increases abundance, increases oxidation, increases expression	2
Arsenic	affects methylation, affects cotreatment, decreases expression, increases abundance	2
Benzo(a)pyrene	decreases methylation, affects methylation	2
Cadmium	decreases expression, increases abundance, increases expression	2
Diethylhexyl Phthalate	decreases expression, increases abundance, increases methylation, decreases reaction	2
Ketoconazole	affects binding, decreases reaction	2
Lithocholic Acid	affects binding, decreases reaction, increases reaction	2
Rotenone	decreases expression, increases expression	2
Dihydrotestosterone	affects binding, decreases reaction, increases activity	2
Tetrachlorodibenzodioxin	decreases reaction, increases expression	2
Aflatoxin B1	increases methylation	2
Cadmium Chloride	decreases expression, increases abundance, increases expression	2
Raloxifene Hydrochloride	affects binding, decreases reaction, decreases expression	2
GSK-J4	increases expression	1
FR900359	affects phosphorylation	1
ethyl (5-(diethylglycyl)-10,11-dihydro-5H-dibenzo(b,f)azepin-3-yl)carbamate	affects binding, decreases reaction, increases reaction	1

ChEMBL screening assays

181 unique, capped per target: 167 binding, 11 admet, 2 functional, 1 toxicity

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1614408	Functional	PUBCHEM_BIOASSAY: Counterscreen for NR2E3 inverse agonists: TR-FRET-based biochemical high throughput dose response assay to identify inverse agonists of the interaction between peroxisome proliferator-activated receptor gamma (PPARg) and n	PubChem BioAssay data set
CHEMBL1772081	Binding	Inhibition of full length HDAC3/NCoR2 assessed as 7-amino-4-methylcoumarin release from fluorophore conjugated substrate after 5 mins by fluorescence assay	Discovery of histone deacetylase 8 selective inhibitors. — Bioorg Med Chem Lett
CHEMBL3860986	ADMET	Inhibition of full length recombinant human HDAC3/NCOR2 expressed in baculovirus infected Sf9 cells using RHKK-Ac as substrate by fluorescence analysis	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

Cellosaurus cell lines

4 cell lines: 3 cancer cell line, 1 transformed cell line

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

Cellosaurus	Name	Category	Sex
CVCL_D7VJ	Ubigene A-549 NCOR2 KO	Cancer cell line	Male
CVCL_D8R2	Ubigene HCT 116 NCOR2 KO	Cancer cell line	Male
CVCL_D9L0	Ubigene HEK293 NCOR2 KO	Transformed cell line	Female
CVCL_E0IT	Ubigene HeLa NCOR2 KO	Cancer cell line	Female

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT00029224	PHASE4	COMPLETED	Treatment With Zoledronic Acid in Patients With Breast Cancer, Multiple Myeloma, and Prostate Cancer With Cancer Related Bone Lesions
NCT00104104	PHASE4	COMPLETED	A Multiple Myeloma Trial in Patients With Bone Metastases
NCT00211211	PHASE4	COMPLETED	FREE Study - Fracture Reduction Evaluation
NCT00242528	PHASE4	WITHDRAWN	Open-label Study, to Evaluate the Safety and Tolerability of Zoledronic Acid in Patients With Bone Lesions Secondary to Multiple Myeloma.
NCT00257114	PHASE4	COMPLETED	Evaluation of VELCADE Given as Retreatment to Multiple Myeloma Patients for Efficacy, Safety and Tolerability
NCT00352703	PHASE4	COMPLETED	PROMPT - Palifermin in Reduction of Oral Mucositis in PBSC Transplantation
NCT00361140	PHASE4	COMPLETED	Busulfan Safety/Efficacy as Conditioning Prior to Hematopoietic Cell Transplantation (HCT)
NCT00622505	PHASE4	COMPLETED	Zoledronic Acid Treatment (Every 4 or 12 Weeks) to Prevent Skeletal Complications in Advanced Multiple Myeloma Participants
NCT00652041	PHASE4	COMPLETED	Bortezomib/Adriamycine/Melfalan/Prednisone (VAMP)/Thalidomide/Cyclophosphamide/Dexamethasone (TaCyDex) or Bortezomib/Melfalan/Prednisone (V-MP)/TaCyDex) in Refractary or Relapsed Multiple Myeloma
NCT00733538	PHASE4	COMPLETED	Stage I Multiple Myeloma Treatment
NCT01087008	PHASE4	COMPLETED	Zoledronic Acid in Patients With Multiple Myeloma and Asymptomatic Biochemical Relapse
NCT01249690	PHASE4	UNKNOWN	Efficacy Study of PAD and TAD in Newly Diagnosed Multiple Myeloma
NCT01410929	PHASE4	WITHDRAWN	Evaluation of Vertebral Compression Fracture Fixation With RF Kyphoplasty in Patients With Multiple Myeloma
NCT01731886	PHASE4	COMPLETED	Lenalidomide and Dexamethasone With/Without Stem Cell Transplant in Patients With Multiple Myeloma
NCT01868828	PHASE4	UNKNOWN	A Study of PAD Versus Velcade, Cyclophosphamide and Dexamethasone (VCD) Treatment in Subjects With Multiple Myeloma
NCT02268890	PHASE4	COMPLETED	A Pharmacokinetic Study of Bortezomib in Taiwanese Participants With Multiple Myeloma
NCT02286830	PHASE4	COMPLETED	Prolonged Protection From Bone Disease in Multiple Myeloma
NCT02559154	PHASE4	UNKNOWN	Modified Bortezomib-based Combination Therapy for Multiple Myeloma
NCT02577783	PHASE4	UNKNOWN	PDD vs PAD to Treat Initially Diagnosed MM
NCT02773550	PHASE4	TERMINATED	Treatment With a Scheme With Low Doses of Bortezomib / Melphalan / Prednisone (MPV) in Patients With Multiple Myeloma
NCT02958969	PHASE4	COMPLETED	Apixaban for Primary Prevention of Venous Thromboembolism in Patients With Multiple Myeloma
NCT03173092	PHASE4	TERMINATED	A Study of Ixazomib (NINLARO®) in Combination With Lenalidomide and Dexamethasone (IRD) for the Treatment of Participants With Multiple Myeloma (MM)
NCT03619252	PHASE4	COMPLETED	Pneumococcal Vaccination of Multiple Myeloma Patients on Novel Agents
NCT03768960	PHASE4	COMPLETED	A Study of DARZALEX (Daratumumab) In Indian Participants With Relapsed and Refractory Multiple Myeloma, Whose Prior Therapy Included a Proteasome Inhibitor and an Immunomodulatory Agent
NCT03829371	PHASE4	ACTIVE_NOT_RECRUITING	STUDY COMPARING TWO STANDARD TREATMENTS IN AUTOLOGOUS STEM CELL TRANSPLANTATION INELIGIBLE POPULATION AFFECTED BY MULTIPLE MYELOMA
NCT03908138	PHASE4	UNKNOWN	RDD Versus VDD in Newly Diagnosed Patients With Multiple Myeloma
NCT04217967	PHASE4	COMPLETED	Ixazomib, Lenalidomide, and Combination for Maintenance in NDMM Patients
NCT04952766	PHASE4	COMPLETED	Study Evaluating SARS-CoV-2 (COVID-19) Humoral Response After BNT162b2 Vaccine in Immunocompromised Adults Compared to Healthy Adults
NCT04989140	PHASE4	UNKNOWN	Study of Pomalidomide, Oral Dexamethasone and Ixazomib in Patients With Relapsed MM Who Have Received Lenalidomide
NCT05183139	PHASE4	WITHDRAWN	A Multicenter In-class Transition Study of Ixazomib Combined With Pomalidomide and Dexamethasone or With Lenalidomide and Dexamethasone in Adults With Relapsed/Refractory Multiple Myeloma
NCT05201781	PHASE4	RECRUITING	A Long-term Study for Participants Previously Treated With Ciltacabtagene Autoleucel
NCT05429515	PHASE4	NOT_YET_RECRUITING	Effect of HFR-SUPRA in the Treatment of Multiple Myeloma-related Acute Kidney Injury
NCT05511428	PHASE4	COMPLETED	Home Based Daratumumab Administration for Patients With Multiple Myeloma
NCT05545202	PHASE4	UNKNOWN	A Randomized, Comparative, Double-blind Trial of Pentaisomaltose and Dimethyl Sulphoxide for Cryoprotection of Hematopoietic Stem Cells in Subjects With Multiple Myeloma or Malignant Lymphoma With a Need for Autologous Transplantation
NCT05555329	PHASE4	COMPLETED	Alternative Dosing Scheme of Pomalidomide 4 mg Every Other Day Versus Pomalidomide 2 mg and 4 mg Every Day; the POMAlternative Study
NCT05722405	PHASE4	RECRUITING	Ixazomib Plus Low-dose Lenalidomide Versus Ixazomib Alone for Maintenance Treatment of High Risk Multiple Myeloma
NCT05855122	PHASE4	UNKNOWN	Safety and ASCT-related Symptom Burden Optimization of Tocilizumab in ASCT Following HD Melphalan Conditioning for Multiple Myeloma Patients
NCT05944783	PHASE4	NOT_YET_RECRUITING	Bioequivalence Studies of Dasatinib 100 Mg
NCT06057402	PHASE4	RECRUITING	Elranatamab Post Trial Access Study for Participants With Multiple Myeloma (MM)
NCT06251076	PHASE4	RECRUITING	Plan Development for Giving Teclistamab in the Outpatient Setting