KDM4A

Summary

KDM4A (lysine demethylase 4A, HGNC:22978) is a protein-coding gene on chromosome 1p34.2-p34.1, encoding Lysine-specific demethylase 4A (O75164). Histone demethylase that specifically demethylates ‘Lys-9’ and ‘Lys-36’ residues of histone H3, thereby playing a central role in histone code.

This gene is a member of the Jumonji domain 2 (JMJD2) family and encodes a protein containing a JmjN domain, a JmjC domain, a JD2H domain, two TUDOR domains, and two PHD-type zinc fingers. This nuclear protein functions as a trimethylation-specific demethylase, converting specific trimethylated histone residues to the dimethylated form, and as a transcriptional repressor.

Source: NCBI Gene 9682 — RefSeq curated summary.

At a glance

• GWAS associations: 15
• Clinical variants (ClinVar): 145 total
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_014663

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:22978
Approved symbol	KDM4A
Name	lysine demethylase 4A
Location	1p34.2-p34.1
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0677, JHDM3A, TDRD14A
Ensembl gene	ENSG00000066135
Ensembl biotype	protein_coding
OMIM	609764
Entrez	9682

Gene structure

Transcript identifiers

Ensembl transcripts: 18 — 15 protein_coding, 2 retained_intron, 1 nonsense_mediated_decay

ENST00000372396, ENST00000463151, ENST00000472265, ENST00000481296, ENST00000485249, ENST00000883343, ENST00000883344, ENST00000883345, ENST00000883346, ENST00000883347, ENST00000883348, ENST00000883349, ENST00000883350, ENST00000924787, ENST00000924788, ENST00000924789, ENST00000951154, ENST00000951155

RefSeq mRNA: 1 — MANE Select: NM_014663 NM_014663

CCDS: CCDS491

Canonical transcript exons

ENST00000372396 — 22 exons

Exon	Start	End
ENSE00000957382	43666954	43667091
ENSE00000957383	43667772	43668019
ENSE00000957384	43669100	43669299
ENSE00000957385	43671505	43671875
ENSE00000957387	43688914	43689095
ENSE00001080535	43697843	43698013
ENSE00001080536	43704020	43704112
ENSE00001080538	43683684	43683804
ENSE00001080539	43703617	43703736
ENSE00001143023	43694709	43694894
ENSE00001143030	43693994	43694102
ENSE00001143039	43692256	43692311
ENSE00001143055	43690845	43691049
ENSE00001841454	43704230	43705518
ENSE00001894244	43650149	43650252
ENSE00003506807	43660298	43660412
ENSE00003515080	43655591	43655766
ENSE00003544170	43691496	43691572
ENSE00003558958	43666452	43666555
ENSE00003565547	43662894	43663087
ENSE00003578520	43665696	43665745
ENSE00003629346	43653137	43653313

Expression profiles

Bgee: expression breadth ubiquitous, 261 present calls, max score 92.65.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 22.7173 / max 309.0581, expressed in 1813 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
2545	12.2055	1794
2544	3.9571	1638
2548	3.2559	1390
2547	2.5915	1334
2546	0.7073	414

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cortical plate	UBERON:0005343	92.65	gold quality
ganglionic eminence	UBERON:0004023	92.13	gold quality
ventricular zone	UBERON:0003053	90.38	gold quality
right adrenal gland cortex	UBERON:0035827	89.65	gold quality
right adrenal gland	UBERON:0001233	89.40	gold quality
adrenal tissue	UBERON:0018303	88.91	gold quality
mucosa of transverse colon	UBERON:0004991	88.81	gold quality
rectum	UBERON:0001052	88.65	gold quality
embryo	UBERON:0000922	88.41	gold quality
left adrenal gland	UBERON:0001234	88.24	gold quality
islet of Langerhans	UBERON:0000006	88.06	gold quality
stromal cell of endometrium	CL:0002255	87.97	gold quality
adrenal gland	UBERON:0002369	87.68	gold quality
left adrenal gland cortex	UBERON:0035825	87.68	gold quality
endometrium epithelium	UBERON:0004811	87.48	gold quality
adrenal cortex	UBERON:0001235	87.28	gold quality
smooth muscle tissue	UBERON:0001135	86.49	gold quality
skin of leg	UBERON:0001511	86.35	gold quality
bone marrow cell	CL:0002092	86.12	gold quality
skin of abdomen	UBERON:0001416	85.94	gold quality
duodenum	UBERON:0002114	85.89	gold quality
type B pancreatic cell	CL:0000169	85.77	gold quality
granulocyte	CL:0000094	85.35	gold quality
leukocyte	CL:0000738	85.04	gold quality
monocyte	CL:0000576	84.85	gold quality
mononuclear cell	CL:0000842	84.82	gold quality
transverse colon	UBERON:0001157	84.82	gold quality
olfactory bulb	UBERON:0002264	84.79	gold quality
Brodmann (1909) area 10	UBERON:0013541	84.78	gold quality
cerebellar cortex	UBERON:0002129	84.64	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	3.55
E-GEOD-124858	no	196.71

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

3 targets.

Target	Regulation
ATG14	Repression
ATG7	Repression
WIPI1	Repression

Upstream regulators (CollecTRI, top): KDM5B, NCOR1, SRF

miRNA regulators (miRDB)

104 targeting KDM4A, 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-8485	100.00	77.57	4731
HSA-MIR-5692A	100.00	74.40	6850
HSA-MIR-4673	100.00	66.64	1490
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-3613-3P	100.00	76.36	7965
HSA-MIR-4645-5P	99.98	65.81	1284
HSA-MIR-485-3P	99.98	70.68	1585
HSA-MIR-539-3P	99.98	70.74	1616
HSA-MIR-607	99.97	73.62	5593
HSA-MIR-7152-3P	99.97	67.47	849
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-5688	99.96	73.23	4504
HSA-MIR-495-3P	99.96	72.81	4197
HSA-MIR-23A-3P	99.95	74.24	3163
HSA-MIR-23B-3P	99.95	74.24	3163
HSA-MIR-23C	99.95	73.92	3192
HSA-MIR-6768-5P	99.92	67.36	1942
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-8063	99.91	69.76	3146
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-137-3P	99.87	74.74	2401
HSA-MIR-3065-3P	99.87	70.25	1407
HSA-MIR-659-3P	99.85	70.69	1620
HSA-MIR-4698	99.84	71.41	4303
HSA-MIR-8080	99.82	67.52	1342
HSA-MIR-4639-5P	99.81	67.37	1028
HSA-MIR-5002-5P	99.76	70.84	1763
HSA-MIR-4255	99.72	67.70	1541

Literature-anchored findings (GeneRIF, showing 40)

• The ability of JMJD2A to associate with retinoblastoma proteins and histone deacetylase 1 implies an important role for this protein in cell proliferation and oncogenesis. (PMID:15927959)
• JMJD2A selectively represses the expression of the achaete scute-like homologue 2 (ASCL2) gene but not other imprinted genes in the same imprinted locus in HeLa cells (PMID:16024779)
• crystal structure of the double tudor domain of JMJD2A both in the presence and absence of a trimethylated H3-K4 peptide (PMID:16601153)
• JHDM3A may function in euchromatin to remove histone methylation marks that are associated with active transcription (PMID:16732292)
• identified two related histone demethylases, JMJD2A and JMJD2D (PMID:17555712)
• how human JMJD2A, which is selective towards tri- and dimethylated histone H3 lysyl residues 9 and 36 (H3K9me3/me2 and H3K36me3/me2), discriminates between methylation states and achieves sequence selectivity for H3K9 (PMID:17589501)
• Crystal structures of the JMJD2A catalytic domain in complex with H3K9me3, H3K36me2 and H3K36me3 peptides are presented. (PMID:17589523)
• Human JMJD2A was expressed in undifferentiated and differentiated ES cells. (PMID:17611647)
• JMJD2A has the unique property of binding trimethylated peptides from two different histone sequences. (PMID:18084306)
• Dynamic Histone H1 Isotype 4 Methylation and Demethylation by Histone Lysine Methyltransferase G9a/KMT1C and the Jumonji Domain-containing JMJD2/KDM4 Proteins (PMID:19144645)
• JHDM3A(GFP)(701) is a suitable catalytic module that can be targeted, under the control of a guide protein, to specific loci where the chromatin H3K9me3 status and the milieu of gene expression are to be modified. (PMID:21148561)
• The authors show that knockdown of JMJD2A, an H3K9me3 demethylase, attenuates viral titers, whereas its overexpression increases Kaposi’s sarcoma-associated herpesvirus reactivation. (PMID:21228229)
• JMJD2A and AR levels were significantly lower in malignant versus benign urothelium, while increased LSD1 levels were observed in malignant urothelium relative to benign; a significant reduction in all three proteins occurred with cancer stage progression (PMID:21400613)
• The expression of JMJD2A was upregulated in human hypertrophic cardiomyopathy patients. (PMID:21555854)
• SKP1-Cul1-F-box and leucine-rich repeat protein 4 (SCF-FbxL4) ubiquitin ligase regulates lysine demethylase 4A (KDM4A)/Jumonji domain-containing 2A (JMJD2A) protein (PMID:21757720)
• these results demonstrate that SCF(FBXO22) regulates changes in histone H3 marks and cognate transcriptional control pathways by controlling KDM4A levels (PMID:21768309)
• JMJD2A gene could result in cell cycle change and proliferation inhibition, and lead to suppress tumor cell invasion and migration. (PMID:21962223)
• data indicate that JMJD2A is a novel promoter of colon cancer cell proliferation and survival, which mediates its effects in p53-dependent and -independent ways (PMID:22134899)
• The authors propose that the RNF8-dependent degradation of JMJD2A regulates DNA repair by controlling the recruitment of 53BP1 at DNA damage sites. (PMID:22373579)
• overexpression of JMJD2A may contribute to breast tumor formation by stimulating ERalpha activity and that JMJD2A may be a breast-relevant oncoprotein. (PMID:22948256)
• The expression of JMJD2A inhibits Ras-mediated CHD5 induction leading to a reduced activity of the p53 pathway. (PMID:23168260)
• JMJD2A regulation has a role in human carcinogenesis through regulation of the G(1)/S transition (PMID:23603248)
• Expression of JMJD2A in infiltrating duct carcinoma is higher than in fibroadenoma, and is associated with ARHI, p53 and ER (PMID:23678541)
• analysis of the nickel-induced inhibition of truncated constructs of JMJD2A and JMJD2C histone demethylases using X-ray absorption spectroscopy (PMID:23692052)
• Findings demonstrate that KDM4A overexpression results in site-specific copy gain of regions amplified in human tumors. (PMID:23871696)
• Those findings demonstrate that JMJD2A regulates gastric cancer growth and serves as an independent prognostic factor, and implicate that JMJD2A may be a promising target for intervention. (PMID:24802408)
• JMJD2A is a promoter of endometrial carcinoma cell proliferation and survival, and is a potential novel drug target. (PMID:24815446)
• The data indicate that JMJD2A could promote breast cancer progression through transcriptional repression of the tumor suppressor ARHI. (PMID:24886710)
• Negative regulation of Sp1 by JMJD2A causes downregulation of Sp1 in highly invasive breast cancer cells. (PMID:25193278)
• A coding single-nucleotide polymorphism in lysine demethylase KDM4A associates with increased sensitivity to mTOR inhibitors (PMID:25564517)
• this review focuses on describing the structure, mechanisms, and function of KDM4A and primarily discusses the role of KDM4A in cancer development and the importance of KDM4A as a potential therapeutic target. [review] (PMID:25633974)
• KDM4 mediates nutrient-limitation signaling that leads to the transcriptional induction of autophagy. (PMID:25660547)
• Studies indicate that histone lysine demethylase (JmjC-KDM) KDM4A protein has been implicated in numerous cancers and cardiovascular diseases. (PMID:25832587)
• Jra recruits the HP1a/KDM4A complex to its gene body region upon osmotic stress to reduce H3K36 methylation levels and disrupt H3K36 methylation-dependent histone deacetylation (PMID:25945750)
• High KDM4A expression is associated with endometrial cancer progression. (PMID:26397136)
• Study demonstrates that JMJD2A contributes to tumorigenesis in non-small cell lung cancer (NSCLC) by regulating miR-150. Additionally, JMJD2A overexpression is associated with a poor prognosis for NSCLC patients. (PMID:26498874)
• This study showed that KDM4A interacts with RNA Polymerase I, associates with active ribosomal RNA genes and is required for serum-induced activation of rDNA transcription. (PMID:26729372)
• these data reveal a JMJD2A/ETV1/YAP1 axis that promotes prostate cancer initiation and that may be a suitable target for therapeutic inhibition. (PMID:26731476)
• KDM4A is regulated by hsa-mir-23a-3p, hsa-mir-23b-3p, and hsa-mir-137. (PMID:26755726)
• Results indicate that SCF(Fbxo22)-KDM4A is an E3 ubiquitin ligase that targets methylated p53 and regulates key senescent processes. (PMID:26868148)

Cross-species orthologs

4 orthologs

Organism	Symbol	Gene ID
mus_musculus	Kdm4a	ENSMUSG00000033326
rattus_norvegicus	Kdm4a	ENSRNOG00000019956
drosophila_melanogaster	Kdm5	FBGN0031759
caenorhabditis_elegans		WBGENE00004319

Paralogs (10): JARID2 (ENSG00000008083), KDM5D (ENSG00000012817), KDM5A (ENSG00000073614), KDM4C (ENSG00000107077), KDM5B (ENSG00000117139), KDM5C (ENSG00000126012), KDM4B (ENSG00000127663), KDM4D (ENSG00000186280), KDM4E (ENSG00000235268), KDM4F (ENSG00000255855)

Protein

Protein identifiers

Lysine-specific demethylase 4A — O75164 (reviewed: O75164)

Alternative names: JmjC domain-containing histone demethylation protein 3A, Jumonji domain-containing protein 2A, [histone H3]-trimethyl-L-lysine(36) demethylase 4A, [histone H3]-trimethyl-L-lysine(9) demethylase 4A

All UniProt accessions (3): O75164, A0A2R8Y7L1, A0A2R8YDF7

UniProt curated annotations — full annotation on UniProt →

Function. Histone demethylase that specifically demethylates ‘Lys-9’ and ‘Lys-36’ residues of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 ‘Lys-4’, H3 ‘Lys-27’ nor H4 ‘Lys-20’. Demethylates trimethylated H3 ‘Lys-9’ and H3 ‘Lys-36’ residue, while it has no activity on mono- and dimethylated residues. Demethylation of Lys residue generates formaldehyde and succinate. Also able to demethylate histone H1-4 methylated at ‘Lys-26’ (H1.4K26me1, H1.4K26me2 and H1.4K26me3). Participates in transcriptional repression of ASCL2 and E2F-responsive promoters via the recruitment of histone deacetylases and NCOR1, respectively. Crucial for muscle differentiation, promotes transcriptional activation of the Myog gene by directing the removal of repressive chromatin marks at its promoter. Lacks the N-terminal demethylase domain.

Subunit / interactions. Interacts with histone deacetylase proteins HDAC1, HDAC2 and HDAC3. Interacts with RB and NCOR1. Interacts with VRK1. Interacts with FBXO22; this interaction promotes KDM4A ubiquitination. (Microbial infection) Interacts with HTLV-1 Tax protein.

Subcellular location. Nucleus.

Tissue specificity. Ubiquitous.

Post-translational modifications. (Microbial infection) SUMOylated by human herpesvirus 8 E3 SUMO-protein ligase K-bZIP/K8 at Lys-471; thereby modulating the chromatin binding and histone demethylase activity of KDM4A. Ubiquitinated by RNF8 and RNF168 following DNA damage, leading to its degradation. Degradation promotes accessibility of H4K20me2 mark for DNA repair protein TP53BP1, which is then recruited. Also ubiquitinated by the SCF(FBXO22) complex; leading to proteasomal degradation.

Activity regulation. Several specific inhibitors are being developed and tested.

Cofactor. Binds 1 Fe(2+) ion per subunit.

Domain organisation. The 2 Tudor domains recognize and bind methylated histone H3 ‘Lys-4’ residue (H3K4me). Double Tudor domain has an interdigitated structure and the unusual fold is required for its ability to bind methylated histone tails. Trimethylated H3 ‘Lys-4’ (H3K4me3) is bound in a cage of 3 aromatic residues, 2 of which are from the Tudor domain 2, while the binding specificity is determined by side-chain interactions involving residues from the Tudor domain 1. The Tudor domains are also able to bind trimethylated histone H3 ‘Lys-9’ (H3K9me3), di- and trimethylated H4 ‘Lys-20’ (H4K20me2 and H4K20me3). Has high affinity for H4K20me2, blocking recruitment of proteins such as TP53BP1.

Similarity. Belongs to the JHDM3 histone demethylase family.

Isoforms (2)

UniProt ID	Names	Canonical?
O75164-1	1	yes
O75164-2	2, deltaN-JMJD2A

RefSeq proteins (1): NP_055478* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR001965	Znf_PHD	Domain
IPR002999	Tudor	Domain
IPR003347	JmjC_dom	Domain
IPR003349	JmjN	Domain
IPR011011	Znf_FYVE_PHD	Homologous_superfamily
IPR013083	Znf_RING/FYVE/PHD	Homologous_superfamily
IPR019787	Znf_PHD-finger	Domain
IPR034732	EPHD	Domain
IPR040477	KDM4-like_Tudor	Domain
IPR047479	Tudor_KDM4A_rpt1	Domain
IPR047481	Tudor_KDM4A_rpt2	Domain
IPR047482	JMJD2A_ePHD	Domain

Pfam: PF02373, PF02375, PF13831, PF13832, PF18104

Enzyme classification (BRENDA):

• EC 1.14.11.27 — [histone H3]-dimethyl-L-lysine36 demethylase (BRENDA: 7 organisms, 38 substrates, 0 inhibitors, 0 Km, 0 kcat entries)
• EC 1.14.11.66 — [histone H3]-trimethyl-L-lysine9 demethylase (BRENDA: 7 organisms, 79 substrates, 168 inhibitors, 23 Km, 14 kcat entries)
• EC 1.14.11.67 — [histone H3]-trimethyl-L-lysine4 demethylase (BRENDA: 13 organisms, 78 substrates, 122 inhibitors, 22 Km, 20 kcat entries)
• EC 1.14.11.69 — [histone H3]-trimethyl-L-lysine36 demethylase (BRENDA: 7 organisms, 48 substrates, 42 inhibitors, 3 Km, 2 kcat entries)
• EC 1.14.99.66 — [histone H3]-N6,N6-dimethyl-L-lysine4 FAD-dependent demethylase (BRENDA: 5 organisms, 74 substrates, 154 inhibitors, 30 Km, 25 kcat entries)

Substrate kinetics (BRENDA)

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

Substrate	Km (mM)	Measurements
H3K4ME2 1-21 PEPTIDE	0.0045–0.035	6
HISTONE H3 N6,N6,N6-TRIMETHYL-L-LYSINE9	0.023–0.048	5
HISTONE H3 N6,N6-DIMETHYL-L-LYSINE9	0.025–0.074	5
[HISTONE H3]-N6,N6-L-DIMETHYLLYSINE4-1-21	0.0045–0.0089	3
2-OXOGLUTARATE	0.0247	2
H31-15K9ME3	0.0232	2
O2	0.173	2
[ACETYLATED HISTONE H3 21MER]-N6,N6,N6-TRIMETHYL	0.0168–0.0955	2
[ACETYLATED HISTONE H3 21MER]-N6,N6-DIMETHYL-L-L	0.0547–0.229	2
[HISTONE H3]-N6,N6-DIMETHYL-L-LYSINE4	0.0107–0.0128	2
[HISTONE H3 PEPTIDE 21MER]-N6-METHYL-L-LYSINE4	0.0113–0.092	2
[HISTONE H3, A7H]-N6,N6,N6-TRIMETHYL-L-LYSINE 9	0.11	1
[HISTONE H3, A7R]-N6,N6,N6-TRIMETHYL-L-LYSINE 9	0.18	1
[HISTONE H3, G12P]-N6,N6,N6-TRIMETHYL-L-LYSINE 9	0.93	1
[HISTONE H3]-N6,N6,N6-TRIMETHYL-L-LYSINE 9	0.071	1

Catalyzed reactions (Rhea), 2 shown:

• N(6),N(6),N(6)-trimethyl-L-lysyl(9)-[histone H3] + 2 2-oxoglutarate + 2 O2 = N(6)-methyl-L-lysyl(9)-[histone H3] + 2 formaldehyde + 2 succinate + 2 CO2 (RHEA:60200)
• N(6),N(6),N(6)-trimethyl-L-lysyl(36)-[histone H3] + 2 2-oxoglutarate + 2 O2 = N(6)-methyl-L-lysyl(36)-[histone H3] + 2 formaldehyde + 2 succinate + 2 CO2 (RHEA:60236)

UniProt features (102 total): strand 26, helix 24, mutagenesis site 13, binding site 11, region of interest 4, domain 4, compositionally biased region 3, site 3, turn 3, zinc finger region 3, modified residue 2, sequence variant 2, initiator methionine 1, chain 1, cross-link 1, splice variant 1

Structure

Experimental structures (PDB)

89 structures, top 30 by resolution.

PDB	Method	Resolution (Å)
9GP4	X-RAY DIFFRACTION	1.59
9GII	X-RAY DIFFRACTION	1.7
6G5X	X-RAY DIFFRACTION	1.78
2QQR	X-RAY DIFFRACTION	1.8
4V2W	X-RAY DIFFRACTION	1.81
5VAR	X-RAY DIFFRACTION	1.83
6G5W	X-RAY DIFFRACTION	1.83
9GLE	X-RAY DIFFRACTION	1.88
2OX0	X-RAY DIFFRACTION	1.95
6H8P	X-RAY DIFFRACTION	1.98
3PDQ	X-RAY DIFFRACTION	1.99
2P5B	X-RAY DIFFRACTION	1.99
5D6W	X-RAY DIFFRACTION	1.99
2OQ6	X-RAY DIFFRACTION	2
2PXJ	X-RAY DIFFRACTION	2
4V2V	X-RAY DIFFRACTION	2
5A7Q	X-RAY DIFFRACTION	2
5ANQ	X-RAY DIFFRACTION	2
2YBP	X-RAY DIFFRACTION	2.02
2Q8C	X-RAY DIFFRACTION	2.05
2Q8E	X-RAY DIFFRACTION	2.05
5F32	X-RAY DIFFRACTION	2.05
5FWE	X-RAY DIFFRACTION	2.05
5F3C	X-RAY DIFFRACTION	2.06
5VGI	X-RAY DIFFRACTION	2.07
5F2S	X-RAY DIFFRACTION	2.08
5TVR	X-RAY DIFFRACTION	2.09
5FYI	X-RAY DIFFRACTION	2.1
2GFA	X-RAY DIFFRACTION	2.1
2OT7	X-RAY DIFFRACTION	2.13

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O75164-F1	72.49	0.43

Functional residue map

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

Catalytic / active sites (3): 945 (histone h3k4me3 binding); 967 (histone h3k4me3 binding); 973 (histone h3k4me3 binding)

Ligand- & substrate-binding residues (11): 132; 188; 190; 198; 206; 234; 240; 241; 276; 306; 308

Post-translational modifications (3): 2, 523, 471

Mutagenesis-validated functional residues (13):

Position	Phenotype
133	abolishes histone demethylase activity; when associated with a-138.
138	abolishes histone demethylase activity; when associated with a-138.
165	abolishes histone demethylase activity; when associated with a-165.
170	abolishes histone demethylase activity; when associated with a-165.
188	abolishes histone demethylase activity without affecting ability to bind h4k20me2.
288–289	displays histone demethylase activity for both dimethylated and h3-k9me3.
288–289	abolishes histone demethylase activity.
471	complete loss of sumo modification by human herpes virus 8 protein k-bzip/k8.
939	impairs binding to h4k20me2, promoting partial recruitment of tp53bp1.
945	impairs binding to h3k4me3.
945	abolishes binding to h3k4me3.
967	abolishes binding to h3k4me3.
973	abolishes binding to h3k4me3.

Function

Pathways and Gene Ontology

Reactome pathways

11 pathways

ID	Pathway
R-HSA-3214842	HDMs demethylate histones
R-HSA-5693565	Recruitment and ATM-mediated phosphorylation of repair and signaling proteins at DNA double strand breaks
R-HSA-9029569	NR1H3 & NR1H2 regulate gene expression linked to cholesterol transport and efflux
R-HSA-162582	Signal Transduction
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-4839726	Chromatin organization
R-HSA-5693532	DNA Double-Strand Break Repair
R-HSA-5693606	DNA Double Strand Break Response
R-HSA-73894	DNA Repair
R-HSA-9006931	Signaling by Nuclear Receptors
R-HSA-9024446	NR1H2 and NR1H3-mediated signaling

MSigDB gene sets: 177 (showing top): GOBP_REGULATION_OF_AUTOPHAGY, WWTAAGGC_UNKNOWN, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, MAZ_Q6, CEBPB_01, PUJANA_CHEK2_PCC_NETWORK, GOBP_NEGATIVE_REGULATION_OF_AUTOPHAGY, GOBP_REGULATION_OF_CATABOLIC_PROCESS, OCT1_03, GOBP_MUSCLE_ADAPTATION, chr1p34, MODULE_123, SCHLOSSER_SERUM_RESPONSE_DN, LASTOWSKA_NEUROBLASTOMA_COPY_NUMBER_DN, GOBP_MUSCLE_HYPERTROPHY

GO Biological Process (7): chromatin remodeling (GO:0006338), regulation of gene expression (GO:0010468), negative regulation of autophagy (GO:0010507), negative regulation of gene expression (GO:0010629), cardiac muscle hypertrophy in response to stress (GO:0014898), negative regulation of DNA-templated transcription (GO:0045892), chromatin organization (GO:0006325)

GO Molecular Function (12): zinc ion binding (GO:0008270), ubiquitin protein ligase binding (GO:0031625), histone demethylase activity (GO:0032452), histone H3K9 demethylase activity (GO:0032454), histone H3K36 demethylase activity (GO:0051864), histone H4K20me2 reader activity (GO:0140005), histone H3K36me2/H3K36me3 demethylase activity (GO:0140681), histone H3K9me2/H3K9me3 demethylase activity (GO:0140684), protein binding (GO:0005515), oxidoreductase activity (GO:0016491), metal ion binding (GO:0046872), dioxygenase activity (GO:0051213)

GO Cellular Component (6): chromatin (GO:0000785), fibrillar center (GO:0001650), nucleus (GO:0005634), nucleoplasm (GO:0005654), pericentric heterochromatin (GO:0005721), cytosol (GO:0005829)

Reactome top-level categories

Rollup of top-8 pathways:

Category	Pathways
Chromatin modifying enzymes	1
DNA Double Strand Break Response	1
NR1H2 and NR1H3-mediated signaling	1
Chromatin organization	1
DNA Repair	1
DNA Double-Strand Break Repair	1
Signal Transduction	1
Signaling by Nuclear Receptors	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	4
gene expression	2
histone H3 demethylase activity	2
2-oxoglutarate-dependent dioxygenase activity	2
chromatin organization	1
regulation of macromolecule biosynthetic process	1
autophagy	1
negative regulation of catabolic process	1
regulation of autophagy	1
regulation of gene expression	1
negative regulation of macromolecule biosynthetic process	1
muscle hypertrophy in response to stress	1
cardiac muscle hypertrophy	1
cardiac muscle adaptation	1
DNA-templated transcription	1
regulation of DNA-templated transcription	1
negative regulation of RNA biosynthetic process	1
cellular component organization	1
transition metal ion binding	1
ubiquitin-like protein ligase binding	1
protein demethylase activity	1
histone modifying activity	1
histone H4 reader activity	1
histone H3K36 demethylase activity	1
histone H3K9 demethylase activity	1
binding	1
catalytic activity	1
cation binding	1
oxidoreductase activity	1
chromosome	1
nucleolus	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
chromosome, centromeric region	1
heterochromatin	1
cytoplasm	1

Protein interactions and networks

STRING

1701 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KDM4A	H3-3A	P06351	972
KDM4A	H3C1	P02295	972
KDM4A	H3C14	Q71DI3	959
KDM4A	H3-5	Q6NXT2	959
KDM4A	H3-4	Q16695	959
KDM4A	H3-7	Q5TEC6	959
KDM4A	KDM1A	O60341	927
KDM4A	JMJD1C	Q15652	893
KDM4A	NCOR1	O75376	860
KDM4A	KDM3A	Q9Y4C1	827
KDM4A	KDM6A	O15550	784
KDM4A	KDM7A	Q6ZMT4	773
KDM4A	KDM6B	O15054	748
KDM4A	Q08EI0	Q08EI0	745
KDM4A	EZH2	Q15910	737

IntAct

52 interactions, top by confidence:

A	B	Type	Score
KDM4A	H4C16	psi-mi:“MI:0407”(direct interaction)	0.740
H4C16	KDM4A	psi-mi:“MI:0407”(direct interaction)	0.740
KDM4A	H3C1	psi-mi:“MI:0407”(direct interaction)	0.700
H3C1	KDM4A	psi-mi:“MI:0407”(direct interaction)	0.700
KDM4A	H3C1	psi-mi:“MI:0403”(colocalization)	0.700
ZNF414	AHCYL1	psi-mi:“MI:0914”(association)	0.640
STK11	KDM4A	psi-mi:“MI:0914”(association)	0.640
KDM4A	H3-4	psi-mi:“MI:0871”(demethylation reaction)	0.620
KDM4A	H3-4	psi-mi:“MI:0407”(direct interaction)	0.620
KDM4A		psi-mi:“MI:0407”(direct interaction)	0.560
ERG	KDM4A	psi-mi:“MI:0915”(physical association)	0.540
ERG	KDM4A	psi-mi:“MI:0407”(direct interaction)	0.540
CCL22	PLXNA2	psi-mi:“MI:0914”(association)	0.530
KDM4A	MCM3	psi-mi:“MI:0914”(association)	0.460

BioGRID (83): KDM4A (Affinity Capture-RNA), KDM4A (Affinity Capture-RNA), CAPZA1 (Co-fractionation), KDM4A (Co-fractionation), KDM4A (Affinity Capture-MS), KDM4A (Affinity Capture-MS), KDM4A (Affinity Capture-MS), KDM4A (Affinity Capture-MS), KDM4A (Affinity Capture-MS), KDM4A (Affinity Capture-MS), PRMT5 (Negative Genetic), KDM4A (Affinity Capture-MS), KDM4A (Affinity Capture-RNA), KDM4A (Affinity Capture-Western), KDM4A (Positive Genetic)

ESM2 similar proteins: A0A0G2JZ79, A1ZA92, A6QQR4, A7E2Z2, A8JQ65, A8WRG3, B3NYS4, B4K6T8, B4R0A5, B6VQ60, F4JZ68, O75164, O94640, P06700, P33294, P42124, P50526, P70351, Q04688, Q08BS4, Q14149, Q15910, Q21921, Q28D84, Q28Z18, Q2NKX8, Q4R381, Q4V863, Q5RD88, Q5RDS6, Q5RDX4, Q60L58, Q61188, Q61IS6, Q640I9, Q6DTM3, Q6PL18, Q757M7, Q8CDM1, Q8K3E5

Diamond homologs: A0A1W2PPD8, A1A5Q5, A1YVX4, B2RXH2, C0SUT9, F4I240, F4I6G4, F4KIX0, O64752, O75164, O94953, P29375, P39956, P41229, P41230, P47156, Q03833, Q10RP4, Q1LVC2, Q23541, Q30DN6, Q336N8, Q38JA7, Q3U2K5, Q3UXZ9, Q53WJ1, Q5F3R2, Q5N712, Q5RD88, Q5XUN4, Q61T02, Q62240, Q62315, Q6B0I6, Q6BDA0, Q6IQX0, Q80Y84, Q8BW72, Q8GUI6, Q8VCD7

SIGNOR signaling

3 interactions.

A	Effect	B	Mechanism
FBXO22	“down-regulates quantity by destabilization”	KDM4A	ubiquitination
“Cullin 1-RBX1-Skp1”	“down-regulates quantity by destabilization”	KDM4A	ubiquitination
2-oxoglutarate(2-)	“up-regulates activity”	KDM4A	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	105
Likely benign	6
Benign	6

Top pathogenic / likely-pathogenic (0)

SpliceAI

4496 predictions. Top by Δscore:

Variant	Effect	Δscore
1:43650215:GAGC:G	donor_gain	1.0000
1:43650218:C:G	donor_gain	1.0000
1:43650309:G:GG	donor_gain	1.0000
1:43653122:AAT:A	acceptor_gain	1.0000
1:43653122:AATGT:A	acceptor_gain	1.0000
1:43653124:T:G	acceptor_gain	1.0000
1:43653310:CAAGG:C	donor_loss	1.0000
1:43653312:AGGT:A	donor_loss	1.0000
1:43653313:GGTAA:G	donor_loss	1.0000
1:43653314:GTAAG:G	donor_loss	1.0000
1:43653315:T:G	donor_loss	1.0000
1:43655577:T:TA	acceptor_gain	1.0000
1:43655579:T:TA	acceptor_gain	1.0000
1:43655586:TTCA:T	acceptor_gain	1.0000
1:43655587:TCA:T	acceptor_loss	1.0000
1:43655587:TCAGG:T	acceptor_gain	1.0000
1:43655588:CA:C	acceptor_loss	1.0000
1:43655588:CAGG:C	acceptor_gain	1.0000
1:43655589:A:AG	acceptor_gain	1.0000
1:43655589:AG:A	acceptor_gain	1.0000
1:43655589:AGGT:A	acceptor_gain	1.0000
1:43655589:AGGTT:A	acceptor_gain	1.0000
1:43655590:G:A	acceptor_gain	1.0000
1:43655590:G:GA	acceptor_gain	1.0000
1:43655590:GGT:G	acceptor_gain	1.0000
1:43655590:GGTT:G	acceptor_gain	1.0000
1:43655590:GGTTG:G	acceptor_gain	1.0000
1:43655760:GCGA:G	donor_gain	1.0000
1:43655762:GA:G	donor_gain	1.0000
1:43655762:GATAA:G	donor_gain	1.0000

AlphaMissense

7043 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
1:43655609:T:A	W53R	1.000
1:43655609:T:C	W53R	1.000
1:43660347:T:A	W122R	1.000
1:43660347:T:C	W122R	1.000
1:43662906:T:A	W148R	1.000
1:43662906:T:C	W148R	1.000
1:43663005:T:A	W181R	1.000
1:43663005:T:C	W181R	1.000
1:43663007:G:C	W181C	1.000
1:43663007:G:T	W181C	1.000
1:43663023:T:A	W187R	1.000
1:43663023:T:C	W187R	1.000
1:43663045:T:C	L194P	1.000
1:43665737:T:C	L222P	1.000
1:43665740:C:A	A223D	1.000
1:43666478:T:C	C234R	1.000
1:43666480:T:G	C234W	1.000
1:43667016:C:A	N280K	1.000
1:43667016:C:G	N280K	1.000
1:43667028:C:A	N284K	1.000
1:43667028:C:G	N284K	1.000
1:43667046:T:A	N290K	1.000
1:43667046:T:G	N290K	1.000
1:43667062:T:A	W296R	1.000
1:43667062:T:C	W296R	1.000
1:43667064:G:C	W296C	1.000
1:43667064:G:T	W296C	1.000
1:43667074:G:C	G300R	1.000
1:43667075:G:A	G300D	1.000
1:43667075:G:T	G300V	1.000

dbSNP variants (sampled 300 via entrez): RS1000045358 (1:43678663 C>G), RS1000077562 (1:43681091 A>G), RS1000082462 (1:43699794 A>C), RS1000107486 (1:43673824 C>T), RS1000190051 (1:43693619 G>A), RS1000258931 (1:43655962 C>T), RS1000259340 (1:43700240 G>C), RS1000385843 (1:43692903 A>G), RS1000393836 (1:43687187 C>A,T), RS1000459942 (1:43674157 G>C), RS1000568178 (1:43668417 G>A), RS1000579834 (1:43668251 G>A), RS1000588862 (1:43666338 A>G,T), RS1000610144 (1:43700459 T>C,G), RS1000644037 (1:43655531 G>A,C)

Disease associations

OMIM: gene MIM:609764 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

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

GWAS associations

15 associations (top):

Study	Trait	p-value
GCST001405_3	Hypertension risk in short sleep duration	4.000000e-06
GCST001663_3	Amyotrophic lateral sclerosis (age of onset)	5.000000e-06
GCST002539_29	Schizophrenia	3.000000e-10
GCST002541_26	Menarche (age at onset)	2.000000e-09
GCST004521_235	Autism spectrum disorder or schizophrenia	4.000000e-10
GCST004750_96	Squamous cell lung carcinoma	4.000000e-06
GCST004946_9	Schizophrenia	1.000000e-12
GCST006803_94	Schizophrenia	1.000000e-11
GCST007326_100	Number of sexual partners	5.000000e-12
GCST007327_222	Smoking status (ever vs never smokers)	4.000000e-13
GCST008768_1	Perceived intensity of sweet substances	5.000000e-06
GCST009524_274	Household income (MTAG)	3.000000e-09
GCST009600_68	Anorexia nervosa, attention-deficit/hyperactivity disorder, autism spectrum disorder, bipolar disorder, major depression, obsessive-compulsive disorder, schizophrenia, or Tourette syndrome (pleiotropy)	7.000000e-14
GCST010002_357	Refractive error	3.000000e-13
GCST90002403_45	Red blood cell count	6.000000e-13

EFO canonical traits (5, from GWAS)

EFO ID	Trait name
EFO:0004847	age at onset
EFO:0004703	age at menarche
EFO:0004318	smoking behavior
EFO:0009695	household income
EFO:0004305	erythrocyte count

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3430889 (PROTEIN COMPLEX), CHEMBL5896 (SINGLE PROTEIN), CHEMBL6195523 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 34,941 (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
CHEMBL550348	DEFERASIROX	4	1,593
CHEMBL556	DEFEROXAMINE	4	25,751
CHEMBL70927	DEFERIPRONE	4	7,561
CHEMBL5314494	ZAVONDEMSTAT	2	36

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

PharmGKB variants

1 variants.

Variant	Genes	Level	Score	#Clin annots	Drugs
rs586339	KDM4A		0.00	0

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — 1.14.11.- Histone demethylases

Most potent curated ligand interactions (3 total), top 3:

Ligand	Action	Affinity	Parameter
compound 6a [PMID: 18942826]	Inhibition	6.15	pIC50
ML324	Inhibition	6.0	pIC50
KDM5 inhibitor N71	Inhibition	5.28	pIC50

Binding affinities (BindingDB)

31 measured of 95 human assays (95 total across all organisms); most potent 31 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
CHEMBL5203308	IC50	33 nM
2-(5-p-tolyl-1H-pyrazol-1- yl)isonicotinic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors
2-(5-(2,4-difluorophenyl)-1H- pyrazol-1-yl)isonicotinic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors
2-(5-(3-hydroxyphenyl)-1H- pyrazol-1-yl)isonicotinic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors
2-(3-phenethyl-1H-pyrazol-1- yl)isonicotinic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors
2-phenyl-1H-pyrrolo[3,2-b] pyridine-7-carboxylic acid	IC50	550 nM	US-9738637: Histone demethylase inhibitors
2-benzyl-1H-pyrrolo[3,2-b] pyridine-7-carboxylic acid	IC50	550 nM	US-9738637: Histone demethylase inhibitors
2-[hydroxy-(3- methoxyphenyl)methyl]-1H- pyrrolo[3,2-b]pyridine-7- carboxylic acid	IC50	550 nM	US-9738637: Histone demethylase inhibitors
2-(phenoxymethyl)-1H- pyrrolo[3,2-b]pyridine-7- carboxylic acid	IC50	550 nM	US-9738637: Histone demethylase inhibitors
2-[hydroxy(oxan-4-yl)methyl]- 1H-pyrrolo[3,2-b]pyridine- 7-carboxylic acid	IC50	550 nM	US-9738637: Histone demethylase inhibitors
2-(4-chloro-3-methoxybenzyl)- 1H-pyrrolo[3,2-b]pyridine-7- carboxylic acid	IC50	550 nM	US-9738637: Histone demethylase inhibitors
2-(3,4-dichlorobenzyl)-1H- pyrrolo[3,2-b]pyridine-7- carboxylic acid	IC50	550 nM	US-9738637: Histone demethylase inhibitors
2-(3,4-dichloro-5-fluorobenzyl)- 1H-pyrrolo[3,2-b]pyridine-7- carboxylic acid	IC50	550 nM	US-9738637: Histone demethylase inhibitors
2-(4-chloro-3-methylbenzyl)-1H- pyrrolo[3,2-b]pyridine-7- carboxylic acid	IC50	550 nM	US-9738637: Histone demethylase inhibitors
2-[4-chloro-3-(trifluoro- methyl)benzyl]-1H-pyrrolo- [3,2-b]pyridine-7-carboxylic acid	IC50	550 nM	US-9738637: Histone demethylase inhibitors
2-[4-chloro-3-(trifluoro-methoxy)benzyl]-1H-pyrrolo[3,2-b]-pyridine-7-carboxylic acid	IC50	550 nM	US-9738637: Histone demethylase inhibitors
2-(1-{2-[2- (dimethylamino)ethoxy]ethyl}- 1H-imidazol-4-yl)pyridine-4- carboxylic acid	IC50	550 nM	US-10273222: Histone demethylase inhibitors
2-(1-{2- [(cyclopropylmethyl)(methyl)- amino]ethyl}-1H-imidazol-4- yl)pyridine-4-carboxylic acid	IC50	550 nM	US-10273222: Histone demethylase inhibitors
2-{1-[2-(pyrrolidin-1-yl)ethyl]- 1H-imidazol-4-yl}-4-(2H- tetrazol-5-yl)pyridine	IC50	550 nM	US-10273222: Histone demethylase inhibitors
2-[1-[2-(5-fluoro-2,3- dihydroindol-1-yl)ethyl]imidazol- 4-yl]pyridine-4-carboxylic acid	IC50	550 nM	US-10273222: Histone demethylase inhibitors
2-[5-[(2-butoxy-4- chlorophenyl)methoxy]pyrazol-1- yl]pyridine-4-carboxylic acid	IC50	5500 nM	US-9908865: Histone demethylase inhibitors
2-[5-[[4-chloro-2-(2- methylpropoxy)phenyl]methoxy] pyrazol-1-yl]pyridine-4-carboxylic acid	IC50	5500 nM	US-9908865: Histone demethylase inhibitors
2-[5-[[4-chloro-2-[(4- fluorophenyl)methoxy]phenyl] methoxy]pyrazol-1-yl]pyridine- 4-carboxylic acid	IC50	5500 nM	US-9908865: Histone demethylase inhibitors
2-[5-[[4-fluoro-2-[(4- fluorophenyl)methoxy]phenyl] methoxy]pyrazol-1-yl]pyridine- 4-carboxylic acid	IC50	5500 nM	US-9908865: Histone demethylase inhibitors
2-[5-[(2-chloro-4- methylphenyl)methoxy]pyrazol-1- yl]pyridine-4-carboxylic acid	IC50	5500 nM	US-9908865: Histone demethylase inhibitors
2-[5-[(2,4- dimethylphenyl)methoxy]pyrazol- 1-yl]pyridine-4-carboxylic acid	IC50	5500 nM	US-9908865: Histone demethylase inhibitors
2-[5-[(2-methoxy-4- methylphenyl)methoxy]pyrazol-1- yl]pyridine-4-carboxylic acid	IC50	5500 nM	US-9908865: Histone demethylase inhibitors
2-[5-[[4-chloro-3- (cyclopropylmethoxy)phenyl] methoxy]pyrazol-1-yl]pyridine- 4-carboxylic acid	IC50	5500 nM	US-9908865: Histone demethylase inhibitors
2-[4-chloro-3-(cyclopropyl- methoxy)benzyl]-1H-pyrrolo[3,2- b]pyridine-7-carboxylic acid	IC50	5500 nM	US-9738637: Histone demethylase inhibitors
2-{1-[2-(pyrrolidin-1-yl)ethyl]- 1H-imidazol-4-yl}pyridine-4- carboxylic acid	IC50	5500 nM	US-10273222: Histone demethylase inhibitors
2-{1-[(1-methylpiperidin-4- yl)methyl]-1H-imidazol-4- yl}pyridine-4-carboxylic acid	IC50	5500 nM	US-10273222: Histone demethylase inhibitors

ChEMBL bioactivities

390 potent at pChembl≥5 of 507 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.70	Ki	2	nM	CHEMBL4438830
8.59	Kd	2.6	nM	CHEMBL4204694
8.52	Ki	3	nM	CHEMBL3774537
8.52	Ki	3	nM	CHEMBL4567766
8.51	Kd	3.1	nM	CHEMBL4205285
8.43	Kd	3.7	nM	CHEMBL4205183
8.40	Ki	4	nM	CHEMBL4447515
8.40	Ki	4	nM	CHEMBL4585876
8.40	Ki	4	nM	CHEMBL4449500
8.30	Ki	5	nM	CHEMBL4573390
8.22	IC50	6	nM	CHEMBL4204694
8.22	IC50	6	nM	CHEMBL5203487
8.08	Kd	8.3	nM	CHEMBL4218774
8.05	Kd	9	nM	CHEMBL4208111
7.96	IC50	11	nM	CHEMBL4209038
7.89	IC50	13	nM	CHEMBL4438830
7.85	Kd	14	nM	CHEMBL4209038
7.85	Kd	14	nM	CHEMBL4206582
7.82	IC50	15	nM	CHEMBL4205285
7.82	IC50	15	nM	CHEMBL4449500
7.80	Kd	16	nM	CHEMBL4206181
7.77	IC50	17	nM	CHEMBL4215000
7.77	IC50	17	nM	CHEMBL4438830
7.68	Kd	21	nM	CHEMBL4211201
7.66	IC50	22	nM	CHEMBL4449500
7.64	IC50	23	nM	CHEMBL4218675
7.64	Kd	23	nM	CHEMBL4215000
7.60	IC50	25	nM	CHEMBL4438830
7.60	IC50	25	nM	CHEMBL4449500
7.58	Ki	26	nM	CHEMBL4525269
7.53	Kd	29.8	nM	CHEMBL4203936
7.53	Kd	29.8	nM	CHEMBL6067729
7.51	IC50	31	nM	CHEMBL4206181
7.48	IC50	33	nM	CHEMBL5203308
7.47	IC50	34	nM	CHEMBL4218774
7.46	IC50	35	nM	CHEMBL4216044
7.42	IC50	38	nM	CHEMBL4438830
7.41	IC50	39	nM	CHEMBL4438830
7.41	IC50	39	nM	CHEMBL4449500
7.39	IC50	41	nM	CHEMBL4211201
7.39	IC50	41	nM	CHEMBL4203936
7.38	Kd	42	nM	CHEMBL4218675
7.38	IC50	42	nM	CHEMBL4532618
7.38	IC50	42	nM	CHEMBL6067729
7.37	IC50	43	nM	CHEMBL4205183
7.31	Kd	49	nM	CHEMBL4218482
7.26	IC50	55	nM	CHEMBL4293252
7.26	IC50	55	nM	CHEMBL4227799
7.26	IC50	55	nM	CHEMBL4228902
7.26	IC50	55	nM	CHEMBL4228384

PubChem BioAssay actives

240 with measured affinity, of 514 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
8-[4-[2-[4-[3-[2-(dimethylamino)ethyl]phenyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556143: Binding affinity to KDM4A (unknown origin)	ki	0.0020	uM
(3R,6S,9S,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R)-12,33-dibenzyl-18-[(2S)-butan-2-yl]-27,30,36-tris(3-carbamimidamidopropyl)-39-[(1S)-1-hydroxyethyl]-24-(hydroxymethyl)-6,9,42-tris[(4-hydroxyphenyl)methyl]-5,8,11,14,17,20,23,26,29,32,35,38,41,44-tetradecaoxo-15-propan-2-yl-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43-tetradecazacyclopentatetracontane-3-carboxamide	1374021: Binding affinity to biotinylated-KDM4A (unknown origin) at 300 nM by bio-layer interferometric method	kd	0.0026	uM
8-[4-[2-[4-(3-chlorophenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556143: Binding affinity to KDM4A (unknown origin)	ki	0.0030	uM
8-[4-[2-[4-(3-pyridin-3-ylphenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556143: Binding affinity to KDM4A (unknown origin)	ki	0.0030	uM
(3R,6S,9S,12S,15R,18S,21S,24S,27S,30S,33S,36S)-27,33-bis[(2S)-butan-2-yl]-21,24,30-tris(3-carbamimidamidopropyl)-18-(hydroxymethyl)-36-[(4-hydroxyphenyl)methyl]-6,12-bis(1H-indol-3-ylmethyl)-15-methyl-9-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	1374021: Binding affinity to biotinylated-KDM4A (unknown origin) at 300 nM by bio-layer interferometric method	kd	0.0031	uM
(3R,6S,9S,12S,18S,21S,24S,27S,30S,33S,36R)-9,33-bis[(2S)-butan-2-yl]-21,30-bis(3-carbamimidamidopropyl)-18-(hydroxymethyl)-36-[(4-hydroxyphenyl)methyl]-6,12-bis(1H-indol-3-ylmethyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-24,27-di(propan-2-yl)-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	1374021: Binding affinity to biotinylated-KDM4A (unknown origin) at 300 nM by bio-layer interferometric method	kd	0.0037	uM
8-[4-[2-[4-[4-[2-(dimethylamino)ethyl]phenyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556143: Binding affinity to KDM4A (unknown origin)	ki	0.0040	uM
8-[4-(2-spiro[1,2-dihydroindene-3,4’-piperidine]-1’-ylethyl)pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556143: Binding affinity to KDM4A (unknown origin)	ki	0.0040	uM
8-[4-[2-[4-(3-fluorophenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556143: Binding affinity to KDM4A (unknown origin)	ki	0.0040	uM
8-[4-[2-[4-(3-chlorophenyl)-4-methylpiperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556143: Binding affinity to KDM4A (unknown origin)	ki	0.0050	uM
(3R,6S,9S,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R)-12,33-dibenzyl-18-[(2S)-butan-2-yl]-27,30,36-tris(3-carbamimidamidopropyl)-39-[(1R)-1-hydroxyethyl]-24-(hydroxymethyl)-6,9,42-tris[(4-hydroxyphenyl)methyl]-5,8,11,14,17,20,23,26,29,32,35,38,41,44-tetradecaoxo-15-propan-2-yl-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43-tetradecazacyclopentatetracontane-3-carboxamide	1885313: Inhibition of KDM4A (unknown origin) measured by AlphaScreen assay	ic50	0.0060	uM
(3R,6S,9S,12S,18S,21S,24S,27S,30S,33S,36S)-27,33-bis[(2S)-butan-2-yl]-21,24,30-tris(3-carbamimidamidopropyl)-18-(hydroxymethyl)-36-[(4-hydroxyphenyl)methyl]-6,12-bis(1H-indol-3-ylmethyl)-4-methyl-9-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	1374021: Binding affinity to biotinylated-KDM4A (unknown origin) at 300 nM by bio-layer interferometric method	kd	0.0083	uM
(3S,9R,12S,15S,18S,24S,27S,30S,33S,36S,39S)-18,33-bis[(2S)-butan-2-yl]-15,27,30,36-tetrakis(3-carbamimidamidopropyl)-24-(hydroxymethyl)-3-[(4-hydroxyphenyl)methyl]-12-(1H-indol-3-ylmethyl)-10-methyl-2,5,11,14,17,20,23,26,29,32,35,38-dodecaoxo-7-thia-1,4,10,13,16,19,22,25,28,31,34,37-dodecazabicyclo[37.3.0]dotetracontane-9-carboxamide	1374021: Binding affinity to biotinylated-KDM4A (unknown origin) at 300 nM by bio-layer interferometric method	kd	0.0090	uM
(3R,6S,9S,12S,18S,21S,24S,27S,30S,33S,36S)-27,33-bis[(2S)-butan-2-yl]-21,24,30-tris(3-carbamimidamidopropyl)-18-(hydroxymethyl)-36-[(4-hydroxyphenyl)methyl]-6,12-bis(1H-indol-3-ylmethyl)-34-methyl-9-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	1374015: Inhibition of KDM4A (unknown origin) expressed in Escherichia coli using biotinylated peptide as substrate pretreated for 15 mins followed by substrate addition by Alphascreen assay	ic50	0.0110	uM
(3S,9R,12S,15S,18S,21R,24S,27S,30S,33S,36S,39S)-18,33-bis[(2S)-butan-2-yl]-15,27,30,36-tetrakis(3-carbamimidamidopropyl)-24-(hydroxymethyl)-3-[(4-hydroxyphenyl)methyl]-12-(1H-indol-3-ylmethyl)-21-methyl-2,5,11,14,17,20,23,26,29,32,35,38-dodecaoxo-7-thia-1,4,10,13,16,19,22,25,28,31,34,37-dodecazabicyclo[37.3.0]dotetracontane-9-carboxamide	1374021: Binding affinity to biotinylated-KDM4A (unknown origin) at 300 nM by bio-layer interferometric method	kd	0.0140	uM
(3R,6S,9S,12S,18S,21S,24S,27S,30S,33S,36S)-27,33-bis[(2S)-butan-2-yl]-21,30-bis(3-carbamimidamidopropyl)-18,24-bis(hydroxymethyl)-36-[(4-hydroxyphenyl)methyl]-6,12-bis(1H-indol-3-ylmethyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-9-propan-2-yl-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	1374021: Binding affinity to biotinylated-KDM4A (unknown origin) at 300 nM by bio-layer interferometric method	kd	0.0160	uM
(3R,6S,9S,12S,15R,18S,21S,24S,27S,30S,33S,36S)-27,33-bis[(2S)-butan-2-yl]-21,24,30-tris(3-carbamimidamidopropyl)-18-(hydroxymethyl)-36-[(4-hydroxyphenyl)methyl]-6,12-bis(1H-indol-3-ylmethyl)-4,15,34-trimethyl-9-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	1374015: Inhibition of KDM4A (unknown origin) expressed in Escherichia coli using biotinylated peptide as substrate pretreated for 15 mins followed by substrate addition by Alphascreen assay	ic50	0.0170	uM
(3S,9R,12S,15S,18S,24S,27S,30S,33S,36S,39S)-30-(4-aminobutyl)-15,33-bis[(2S)-butan-2-yl]-27-[3-(diaminomethylideneamino)propyl]-24,36-bis(hydroxymethyl)-3-[(4-hydroxyphenyl)methyl]-12,18-bis(1H-indol-3-ylmethyl)-2,5,11,14,17,20,23,26,29,32,35,38-dodecaoxo-7-thia-1,4,10,13,16,19,22,25,28,31,34,37-dodecazabicyclo[37.3.0]dotetracontane-9-carboxamide	1374021: Binding affinity to biotinylated-KDM4A (unknown origin) at 300 nM by bio-layer interferometric method	kd	0.0210	uM
(3R,6S,9S,12S,18S,21S,24S,27S,30S,33S,36S)-27,33-bis[(2S)-butan-2-yl]-21,24,30-tris(3-carbamimidamidopropyl)-18-(hydroxymethyl)-36-[(4-hydroxyphenyl)methyl]-6,12-bis(1H-indol-3-ylmethyl)-9-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	1374015: Inhibition of KDM4A (unknown origin) expressed in Escherichia coli using biotinylated peptide as substrate pretreated for 15 mins followed by substrate addition by Alphascreen assay	ic50	0.0230	uM
8-[4-[1-(cyclobutylmethyl)piperidin-4-yl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556143: Binding affinity to KDM4A (unknown origin)	ki	0.0260	uM
(3R,6S,9S,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R)-33-(2-amino-2-oxoethyl)-15,27-bis(3-carbamimidamidopropyl)-30-[(1R)-1-hydroxyethyl]-24-(hydroxymethyl)-9,36,42-tris[(4-hydroxyphenyl)methyl]-6,12,18-tris(1H-indol-3-ylmethyl)-5,8,11,14,17,20,23,26,29,32,35,38,41,44-tetradecaoxo-39-propan-2-yl-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43-tetradecazacyclopentatetracontane-3-carboxamide	1374023: Binding affinity to N-terminal His6-tagged KDM4A (1 to 359 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) Rosetta by bio-layer interferometric method	kd	0.0298	uM
(3R,6S,9S,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R)-33-(2-amino-2-oxoethyl)-15,27-bis(3-carbamimidamidopropyl)-6,30-bis[(1R)-1-hydroxyethyl]-24-(hydroxymethyl)-9,36,42-tris[(4-hydroxyphenyl)methyl]-12,18-bis(1H-indol-3-ylmethyl)-5,8,11,14,17,20,23,26,29,32,35,38,41,44-tetradecaoxo-39-propan-2-yl-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43-tetradecazacyclopentatetracontane-3-carboxamide	1885313: Inhibition of KDM4A (unknown origin) measured by AlphaScreen assay	ic50	0.0330	uM
3-[[(1R)-6-(N-methylanilino)-1,2,3,4-tetrahydronaphthalen-1-yl]methylamino]pyridine-4-carboxylic acid	1885273: Inhibition of KDM4A (unknown origin) using H3K9me3 as substrate and measured by LANCE TR-FRET assay	ic50	0.0350	uM
2-[(5R,8S,11S,14S,17S,20S,23S,29S,32S,35S,38R,41R,44R)-44-amino-20,32-bis(3-carbamimidamidopropyl)-41-[(1S)-1-hydroxyethyl]-17-[(1R)-1-hydroxyethyl]-23-(hydroxymethyl)-5,11,38-tris[(4-hydroxyphenyl)methyl]-29,35-bis(1H-indol-3-ylmethyl)-2,4,7,10,13,16,19,22,25,28,31,34,37,40,43-pentadecaoxo-8-propan-2-yl-1-thia-3,6,9,12,15,18,21,24,27,30,33,36,39,42-tetradecazacyclopentatetracont-14-yl]acetamide	1584425: Inhibition of N-terminal His6-tagged KDM4A (1 to 359 residues) (unknown origin) expressed in Escherichia coli BL21(DE3) preincubated for 15 mins followed by biotin-labeled peptide substrate addition and measured after 1 hr by Alpha screen assay	ic50	0.0420	uM
(3S,9R,12S,15S,18S,24S,27S,30S,33S,36S,39S)-36-(4-aminobutyl)-15-[(2S)-butan-2-yl]-27-[3-(diaminomethylideneamino)propyl]-24-(hydroxymethyl)-3-[(4-hydroxyphenyl)methyl]-12-(1H-indol-3-ylmethyl)-18-(2-methylpropyl)-2,5,11,14,17,20,23,26,29,32,35,38-dodecaoxo-30,33-di(propan-2-yl)-7-thia-1,4,10,13,16,19,22,25,28,31,34,37-dodecazabicyclo[37.3.0]dotetracontane-9-carboxamide	1374021: Binding affinity to biotinylated-KDM4A (unknown origin) at 300 nM by bio-layer interferometric method	kd	0.0490	uM
8-[4-[2-[4-[3-(2-morpholin-4-ylethyl)phenyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556101: Inhibition of N-terminal His-tagged recombinant human KDM4A (1 to 359 residues) expressed in Escherichia coli assessed as decrease in demethylation of substrate using peptide (ARTKQTARK(Me3)STGGKAPRKQLA-GGKbiotin) as substrate and 2OG as cosubstrate pre-incubated for 10 mins before substrate addition followed by centrifugation for 1 min and measured after 20 mins by AlphaScreen assay	ic50	0.0590	uM
8-[4-[2-[4-(4-pyrimidin-5-ylphenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556101: Inhibition of N-terminal His-tagged recombinant human KDM4A (1 to 359 residues) expressed in Escherichia coli assessed as decrease in demethylation of substrate using peptide (ARTKQTARK(Me3)STGGKAPRKQLA-GGKbiotin) as substrate and 2OG as cosubstrate pre-incubated for 10 mins before substrate addition followed by centrifugation for 1 min and measured after 20 mins by AlphaScreen assay	ic50	0.0680	uM
8-[4-[2-[4-[3-(pyrrolidin-1-ylmethyl)-5-(trifluoromethyl)phenyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556101: Inhibition of N-terminal His-tagged recombinant human KDM4A (1 to 359 residues) expressed in Escherichia coli assessed as decrease in demethylation of substrate using peptide (ARTKQTARK(Me3)STGGKAPRKQLA-GGKbiotin) as substrate and 2OG as cosubstrate pre-incubated for 10 mins before substrate addition followed by centrifugation for 1 min and measured after 20 mins by AlphaScreen assay	ic50	0.0710	uM
8-[4-[2-[4-[4-(2-morpholin-4-ylethyl)phenyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556101: Inhibition of N-terminal His-tagged recombinant human KDM4A (1 to 359 residues) expressed in Escherichia coli assessed as decrease in demethylation of substrate using peptide (ARTKQTARK(Me3)STGGKAPRKQLA-GGKbiotin) as substrate and 2OG as cosubstrate pre-incubated for 10 mins before substrate addition followed by centrifugation for 1 min and measured after 20 mins by AlphaScreen assay	ic50	0.0770	uM
8-[4-[2-[4-(3,5-dichlorophenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282542: Inhibition of human N-terminal His-tagged KDM4A (1 to 359 residues) expressed in Escherichia coli using biotin-H3K9me3 as substrate preincubated for 10 mins measured after 20 mins by alphascreen assay	ic50	0.0800	uM
(3R,6S,9S,12S,18S,21S,24S,27S,30S,33S,36S)-30-[(2S)-butan-2-yl]-21,24-bis[3-(diaminomethylideneamino)propyl]-18-(hydroxymethyl)-36-[(4-hydroxyphenyl)methyl]-6-(1H-indol-3-ylmethyl)-12,33-bis(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-9,27-di(propan-2-yl)-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	1374015: Inhibition of KDM4A (unknown origin) expressed in Escherichia coli using biotinylated peptide as substrate pretreated for 15 mins followed by substrate addition by Alphascreen assay	ic50	0.0810	uM
8-[4-[2-[4-[3-(pyrrolidin-1-ylmethyl)phenyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556101: Inhibition of N-terminal His-tagged recombinant human KDM4A (1 to 359 residues) expressed in Escherichia coli assessed as decrease in demethylation of substrate using peptide (ARTKQTARK(Me3)STGGKAPRKQLA-GGKbiotin) as substrate and 2OG as cosubstrate pre-incubated for 10 mins before substrate addition followed by centrifugation for 1 min and measured after 20 mins by AlphaScreen assay	ic50	0.0830	uM
8-[4-[2-[4-(3-pyrimidin-5-ylphenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556101: Inhibition of N-terminal His-tagged recombinant human KDM4A (1 to 359 residues) expressed in Escherichia coli assessed as decrease in demethylation of substrate using peptide (ARTKQTARK(Me3)STGGKAPRKQLA-GGKbiotin) as substrate and 2OG as cosubstrate pre-incubated for 10 mins before substrate addition followed by centrifugation for 1 min and measured after 20 mins by AlphaScreen assay	ic50	0.0880	uM
2-[5-[(4-chloro-2-methylphenyl)methoxy]pyrazol-1-yl]pyridine-4-carboxylic acid	1391736: Inhibition of KDM4A (unknown origin)	ic50	0.0990	uM
2-[(4-chloro-3-methoxyphenyl)methoxy]-1H-pyrrolo[3,2-b]pyridine-7-carboxylic acid	1289413: Inhibition of recombinant human N-terminal His-tagged KDM4A (1 to 350 residues) expressed in Escherichia coli using biotin-H3K9me3 substrate incubated for 30 mins by TR-FRET assay	ic50	0.1000	uM
2-[[4-chloro-3-(trifluoromethoxy)phenyl]methoxy]-1H-pyrrolo[3,2-b]pyridine-7-carboxylic acid	1289413: Inhibition of recombinant human N-terminal His-tagged KDM4A (1 to 350 residues) expressed in Escherichia coli using biotin-H3K9me3 substrate incubated for 30 mins by TR-FRET assay	ic50	0.1000	uM
3-(furan-2-ylmethylamino)pyridine-4-carboxylic acid	1282652: Inhibition of KDM4A (unknown origin) using H3K9Me3 peptide as substrate assessed as demethylation of substrate by Rapidfire mass spectrometric analysis	ic50	0.1000	uM
2-(1-methylimidazol-4-yl)pyridine-4-carboxylic acid	1289413: Inhibition of recombinant human N-terminal His-tagged KDM4A (1 to 350 residues) expressed in Escherichia coli using biotin-H3K9me3 substrate incubated for 30 mins by TR-FRET assay	ic50	0.1000	uM
2-[[[2-[2-(dimethylamino)ethyl-ethylamino]-2-oxoethyl]amino]methyl]pyridine-4-carboxylic acid	1289435: Inhibition of recombinant human N-terminal His-tagged KDM4A (1 to 350 residues) expressed in Escherichia coli using methylated biotin-H3K9 substrate preincubated for 10 mins followed by substrate addition measured after 10 mins by AlphaLisa assay	ic50	0.1000	uM
3-[(3-methylthiophen-2-yl)methylamino]pyridine-4-carboxylic acid	1282652: Inhibition of KDM4A (unknown origin) using H3K9Me3 peptide as substrate assessed as demethylation of substrate by Rapidfire mass spectrometric analysis	ic50	0.1000	uM
8-[4-[2-[4-(4-pyridin-4-ylphenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556101: Inhibition of N-terminal His-tagged recombinant human KDM4A (1 to 359 residues) expressed in Escherichia coli assessed as decrease in demethylation of substrate using peptide (ARTKQTARK(Me3)STGGKAPRKQLA-GGKbiotin) as substrate and 2OG as cosubstrate pre-incubated for 10 mins before substrate addition followed by centrifugation for 1 min and measured after 20 mins by AlphaScreen assay	ic50	0.1030	uM
8-[4-[2-[4-(4-methylsulfonylphenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282542: Inhibition of human N-terminal His-tagged KDM4A (1 to 359 residues) expressed in Escherichia coli using biotin-H3K9me3 as substrate preincubated for 10 mins measured after 20 mins by alphascreen assay	ic50	0.1090	uM
8-[4-[2-[4-(2,4-difluorophenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282542: Inhibition of human N-terminal His-tagged KDM4A (1 to 359 residues) expressed in Escherichia coli using biotin-H3K9me3 as substrate preincubated for 10 mins measured after 20 mins by alphascreen assay	ic50	0.1100	uM
4-[1-[2-[1-(4-oxo-3H-pyrido[3,4-d]pyrimidin-8-yl)pyrazol-4-yl]ethyl]piperidin-4-yl]benzonitrile	1282542: Inhibition of human N-terminal His-tagged KDM4A (1 to 359 residues) expressed in Escherichia coli using biotin-H3K9me3 as substrate preincubated for 10 mins measured after 20 mins by alphascreen assay	ic50	0.1180	uM
8-[4-[2-[4-(4-methoxyphenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282542: Inhibition of human N-terminal His-tagged KDM4A (1 to 359 residues) expressed in Escherichia coli using biotin-H3K9me3 as substrate preincubated for 10 mins measured after 20 mins by alphascreen assay	ic50	0.1230	uM
3-(benzylamino)pyridine-4-carboxylic acid	1282652: Inhibition of KDM4A (unknown origin) using H3K9Me3 peptide as substrate assessed as demethylation of substrate by Rapidfire mass spectrometric analysis	ic50	0.1259	uM
8-[4-[2-[4-[(4-chlorophenyl)methyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282542: Inhibition of human N-terminal His-tagged KDM4A (1 to 359 residues) expressed in Escherichia coli using biotin-H3K9me3 as substrate preincubated for 10 mins measured after 20 mins by alphascreen assay	ic50	0.1260	uM
8-[4-[2-[4-[3-(trifluoromethyl)phenyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282542: Inhibition of human N-terminal His-tagged KDM4A (1 to 359 residues) expressed in Escherichia coli using biotin-H3K9me3 as substrate preincubated for 10 mins measured after 20 mins by alphascreen assay	ic50	0.1280	uM
8-[4-[2-[4-(4-pyridin-3-ylphenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556101: Inhibition of N-terminal His-tagged recombinant human KDM4A (1 to 359 residues) expressed in Escherichia coli assessed as decrease in demethylation of substrate using peptide (ARTKQTARK(Me3)STGGKAPRKQLA-GGKbiotin) as substrate and 2OG as cosubstrate pre-incubated for 10 mins before substrate addition followed by centrifugation for 1 min and measured after 20 mins by AlphaScreen assay	ic50	0.1310	uM
8-[4-[2-[4-(1,3-benzodioxol-5-ylmethyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282542: Inhibition of human N-terminal His-tagged KDM4A (1 to 359 residues) expressed in Escherichia coli using biotin-H3K9me3 as substrate preincubated for 10 mins measured after 20 mins by alphascreen assay	ic50	0.1360	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
cobaltous chloride	affects binding, decreases abundance, increases reaction, increases expression, decreases activity (+1 more)	3
sodium arsenite	increases expression, decreases expression, affects cotreatment, increases abundance	2
Benzo(a)pyrene	affects methylation, decreases methylation, increases methylation	2
Valproic Acid	affects expression, decreases expression	2
Aflatoxin B1	increases methylation	2
FR900359	affects phosphorylation	1
TAK-243	increases sumoylation	1
trichostatin A	decreases activity, decreases expression, increases expression	1
beta-lapachone	increases expression	1
arsenite	affects binding, decreases reaction	1
manganese chloride	affects cotreatment, increases abundance, increases expression	1
benzo(e)pyrene	affects methylation	1
di-n-butylphosphoric acid	affects expression	1
CGP 52608	affects binding, increases reaction	1
K 7174	increases expression	1
(+)-JQ1 compound	increases expression	1
Sunitinib	increases expression	1
Vorinostat	decreases expression	1
Leflunomide	decreases expression	1
Arsenic	increases expression, affects cotreatment, increases abundance	1
Berberine	increases expression	1
Caffeine	affects phosphorylation	1
Deferoxamine	decreases activity, decreases expression	1
Doxorubicin	increases expression	1
Estradiol	decreases expression	1
Manganese	affects cotreatment, increases abundance, increases expression	1
Methapyrilene	affects methylation	1
Nitric Oxide	increases expression	1
Oxygen	increases expression, affects reaction, affects binding, decreases abundance, increases reaction	1
Progesterone	increases expression	1

ChEMBL screening assays

180 unique, capped per target: 177 binding, 3 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3365863	Binding	Inhibition of KDM4A/KDM4B in human LNCaP cells assessed as increase in H3K9me3 level after 24 hrs days by Western blotting	KDM4B as a target for prostate cancer: structural analysis and selective inhibition by a novel inhibitor. — J Med Chem
CHEMBL1737991	Functional	PUBCHEM_BIOASSAY: qHTS Assay for Inhibitors of JMJD2A-Tudor Domain. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AID504402]	PubChem BioAssay data set

Cellosaurus cell lines

3 cell lines: 3 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SU27	HAP1 KDM4A (-) 1	Cancer cell line	Male
CVCL_SU28	HAP1 KDM4A (-) 2	Cancer cell line	Male
CVCL_SU29	HAP1 KDM4A (-) 3	Cancer cell line	Male

Clinical trials (associated diseases)

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