KDM4E

Summary

KDM4E (lysine demethylase 4E, HGNC:37098) is a protein-coding gene on chromosome 11q21, encoding Lysine-specific demethylase 4E (B2RXH2). Histone demethylase that demethylates trimethylated ‘Lys-9’ of histone H3 into monomethylated form, thereby playing a central role in histone code.

The protein encoded by this intronless gene is a member of a large family of histone lysine demethylases, which use oxygen and 2-oxoglutarate to demethylate di- and trimethylated lys9 of histone H3. Derepression of genes by demethylases is sometimes involved in viral infection or carcinogenesis, so inhibitors of these enzymes are desired.

Source: NCBI Gene 390245 — RefSeq curated summary.

At a glance

• GWAS associations: 1
• Clinical variants (ClinVar): 107 total
• Druggable target: yes — 356 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_001161630

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:37098
Approved symbol	KDM4E
Name	lysine demethylase 4E
Location	11q21
Locus type	gene with protein product
Status	Approved
Aliases	JMJD2E, KDM5E
Ensembl gene	ENSG00000235268
Ensembl biotype	protein_coding
OMIM	616581
Entrez	390245

Gene structure

Transcript identifiers

Ensembl transcripts: 1 — 1 protein_coding

ENST00000450979

RefSeq mRNA: 1 — MANE Select: NM_001161630 NM_001161630

CCDS: CCDS44713

Canonical transcript exons

ENST00000450979 — 1 exons

Exon	Start	End
ENSE00001783902	95025258	95027596

Expression profiles

Bgee: expression breadth broad, 14 present calls, max score 80.23.

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	80.23	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	79.41	silver quality
placenta	UBERON:0001987	45.82	gold quality
tonsil	UBERON:0002372	43.58	gold quality
sural nerve	UBERON:0015488	42.88	gold quality
apex of heart	UBERON:0002098	41.07	silver quality
gall bladder	UBERON:0002110	40.85	gold quality
bone marrow cell	CL:0002092	40.42	gold quality
saliva-secreting gland	UBERON:0001044	40.04	silver quality
smooth muscle tissue	UBERON:0001135	39.88	silver quality
minor salivary gland	UBERON:0001830	39.01	silver quality
right lobe of thyroid gland	UBERON:0001119	38.47	silver quality
urinary bladder	UBERON:0001255	38.34	silver quality
muscle tissue	UBERON:0002385	38.15	gold quality
skeletal muscle tissue	UBERON:0001134	37.97	gold quality
lower esophagus mucosa	UBERON:0035834	37.41	gold quality
colonic epithelium	UBERON:0000397	37.20	gold quality
thoracic mammary gland	UBERON:0005200	36.98	silver quality
lymph node	UBERON:0000029	36.50	gold quality
granulocyte	CL:0000094	36.49	gold quality
ventricular zone	UBERON:0003053	36.48	gold quality
cortical plate	UBERON:0005343	36.47	gold quality
endometrium	UBERON:0001295	36.25	gold quality
pituitary gland	UBERON:0000007	36.18	silver quality
ganglionic eminence	UBERON:0004023	35.49	gold quality
right ovary	UBERON:0002118	35.11	gold quality
bone marrow	UBERON:0002371	35.05	gold quality
right coronary artery	UBERON:0001625	35.03	gold quality
right lung	UBERON:0002167	34.32	gold quality
mucosa of transverse colon	UBERON:0004991	34.28	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 0.

Experiment	Marker?	Max mean expression
E-ANND-3	no	2.29

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

43 targeting KDM4E, 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-223-3P	99.99	70.14	1140
HSA-MIR-512-3P	99.97	67.35	1049
HSA-MIR-124-3P	99.89	73.74	3043
HSA-MIR-506-3P	99.89	73.55	3057
HSA-MIR-6780A-5P	99.88	66.69	2776
HSA-MIR-5582-3P	99.86	72.48	4221
HSA-MIR-1273H-5P	99.77	66.32	2471
HSA-MIR-1299	99.77	71.24	2389
HSA-MIR-6505-5P	99.73	69.25	1595
HSA-MIR-30B-3P	99.70	65.76	2325
HSA-MIR-3689A-3P	99.70	65.73	2306
HSA-MIR-3689B-3P	99.70	65.71	2311
HSA-MIR-3689C	99.70	65.71	2311
HSA-MIR-6779-5P	99.70	65.76	2363
HSA-MIR-4690-5P	99.65	66.24	813
HSA-MIR-10394-5P	99.65	66.83	1852
HSA-MIR-1205	99.65	66.76	1826
HSA-MIR-875-3P	99.63	69.47	2548
HSA-MIR-6733-3P	99.54	67.80	1281
HSA-MIR-7106-5P	99.53	67.47	3574
HSA-MIR-3923	99.52	69.21	446
HSA-MIR-4441	99.49	66.56	3216
HSA-MIR-766-5P	99.47	67.91	2225
HSA-MIR-584-3P	99.35	67.69	1082
HSA-MIR-4641	99.28	66.64	744
HSA-MIR-5582-5P	99.27	71.42	1879
HSA-MIR-6852-5P	99.17	66.69	2073
HSA-MIR-4270	99.02	66.26	1987
HSA-MIR-219A-1-3P	98.91	67.87	639
HSA-MIR-6754-5P	98.60	65.54	1627

Literature-anchored findings (GeneRIF, showing 1)

• Results indicate that the histone demethylase activity is regulated by oxygen availability. (PMID:23092293)

Cross-species orthologs

3 orthologs

Organism	Symbol	Gene ID
danio_rerio	kdm4c	ENSDARG00000061504
drosophila_melanogaster	Kdm5	FBGN0031759
caenorhabditis_elegans		WBGENE00004319

Paralogs (10): JARID2 (ENSG00000008083), KDM5D (ENSG00000012817), KDM4A (ENSG00000066135), KDM5A (ENSG00000073614), KDM4C (ENSG00000107077), KDM5B (ENSG00000117139), KDM5C (ENSG00000126012), KDM4B (ENSG00000127663), KDM4D (ENSG00000186280), KDM4F (ENSG00000255855)

Protein

Protein identifiers

Lysine-specific demethylase 4E — B2RXH2 (reviewed: B2RXH2)

Alternative names: KDM4D-like protein, Lysine-specific demethylase 4D-like, [histone H3]-trimethyl-L-lysine(9) demethylase 4E

All UniProt accessions (1): B2RXH2

UniProt curated annotations — full annotation on UniProt →

Function. Histone demethylase that demethylates trimethylated ‘Lys-9’ of histone H3 into monomethylated form, thereby playing a central role in histone code. Also demethylates trimethylated ‘Lys-56’ of histone H3 (H3K9me3) to generate the monomethylated state (H3K56me1).

Subcellular location. Nucleus.

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

Similarity. Belongs to the JHDM3 histone demethylase family.

RefSeq proteins (1): NP_001155102* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR003347	JmjC_dom	Domain
IPR003349	JmjN	Domain

Pfam: PF02373, PF02375

Enzyme classification (BRENDA):

• 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.B19 — (BRENDA: organisms, substrates, inhibitors, Km, kcat entries)

Substrate kinetics (BRENDA)

9 substrates with measured Km, best-characterized 9. Km ranges are aggregated across organisms/conditions.

Substrate	Km (mM)	Measurements
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
2-OXOGLUTARATE	0.0247	2
H31-15K9ME3	0.0232	2
O2	0.173	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), 5 shown:

• N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3] + 2-oxoglutarate + O2 = N(6)-methyl-L-lysyl(9)-[histone H3] + formaldehyde + succinate + CO2 (RHEA:60192)
• 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(9)-[histone H3] + 2-oxoglutarate + O2 = N(6),N(6)-dimethyl-L-lysyl(9)-[histone H3] + formaldehyde + succinate + CO2 (RHEA:60204)
• N(6),N(6),N(6)-trimethyl-L-lysyl(56)-[histone H3] + 2-oxoglutarate + O2 = N(6),N(6)-dimethyl-L-lysyl(56)-[histone H3] + formaldehyde + succinate + CO2 (RHEA:85927)
• N(6),N(6)-dimethyl-L-lysyl(56)-[histone H3] + 2-oxoglutarate + O2 = N(6)-methyl-L-lysyl(56)-[histone H3] + formaldehyde + succinate + CO2 (RHEA:85931)

UniProt features (55 total): helix 16, strand 15, binding site 11, sequence variant 4, turn 4, domain 2, chain 1, region of interest 1, compositionally biased region 1

Structure

Experimental structures (PDB)

1 structures.

PDB	Method	Resolution (Å)
2W2I	X-RAY DIFFRACTION	2.1

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-B2RXH2-F1	76.85	0.59

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 (11): 235; 241; 242; 277; 307; 309; 133; 189; 191; 199; 207

Function

Pathways and Gene Ontology

Reactome pathways

3 pathways

ID	Pathway
R-HSA-9819196	Zygotic genome activation (ZGA)
R-HSA-1266738	Developmental Biology
R-HSA-9816359	Maternal to zygotic transition (MZT)

MSigDB gene sets: 24 (showing top): GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GOBP_CHROMATIN_REMODELING, GOMF_DEMETHYLASE_ACTIVITY, chr11q21, GOMF_DIOXYGENASE_ACTIVITY, GOMF_HISTONE_H3K9_DEMETHYLASE_ACTIVITY, MIR875_3P, MIR4441, MIR6780A_5P, MIR6505_5P, MIR6852_5P, MIR4270, MIR4308, MIR6754_5P, GOMF_PROTEIN_DEMETHYLASE_ACTIVITY

GO Biological Process (3): chromatin remodeling (GO:0006338), regulation of gene expression (GO:0010468), chromatin organization (GO:0006325)

GO Molecular Function (5): histone H3K9 demethylase activity (GO:0032454), metal ion binding (GO:0046872), histone H3K9me2/H3K9me3 demethylase activity (GO:0140684), oxidoreductase activity (GO:0016491), dioxygenase activity (GO:0051213)

GO Cellular Component (3): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654)

Reactome top-level categories

Rollup of top-2 pathways:

Category	Pathways
Maternal to zygotic transition (MZT)	1
Developmental Biology	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
chromatin organization	1
gene expression	1
regulation of macromolecule biosynthetic process	1
cellular component organization	1
histone H3 demethylase activity	1
cation binding	1
2-oxoglutarate-dependent dioxygenase activity	1
histone H3K9 demethylase activity	1
catalytic activity	1
oxidoreductase activity	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1

Protein interactions and networks

STRING

424 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KDM4E	JMJD1C	Q15652	698
KDM4E	KDM2A	Q9Y2K7	636
KDM4E	PHF8	Q9UPP1	617
KDM4E	KDM3A	Q9Y4C1	614
KDM4E	KDM6B	O15054	585
KDM4E	ADH5	P11766	555
KDM4E	KDM7A	Q6ZMT4	528
KDM4E	KDM3B	Q7LBC6	520
KDM4E	KDM1A	O60341	509
KDM4E	JMJD6	Q6NYC1	494
KDM4E	KDM8	Q8N371	489
KDM4E	EGLN1	Q9GZT9	480
KDM4E	Q08EI0	Q08EI0	463
KDM4E	PHF2	O75151	454
KDM4E	KDM2B	Q8NHM5	447

IntAct

0 interactions, top by confidence:

ESM2 similar proteins: A0A1W2PPD8, A1A5Q5, A2A3K4, A4H5X5, A7E379, B2RXH2, C0SUT9, D3ZKV9, F5HB62, O19132, O36371, O54705, O60291, O75164, O94953, P03177, P33802, P35228, Q1HVD1, Q29RJ0, Q3KSQ2, Q3U2K5, Q3UPF5, Q53WJ1, Q5R4R7, Q5R978, Q5RD88, Q5VW22, Q5VWQ0, Q6B0I6, Q6EEF3, Q6EMB2, Q6PI47, Q6X4W1, Q80T69, Q80TL4, Q8BFX3, Q8BW72, Q8CHB8, Q8K3Y6

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

1 interactions.

A	Effect	B	Mechanism
2-oxoglutarate(2-)	“up-regulates activity”	KDM4E	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	99
Likely benign	6
Benign	2

Top pathogenic / likely-pathogenic (0)

SpliceAI

8 predictions. Top by Δscore:

Variant	Effect	Δscore
11:95025894:CAGAA:C	acceptor_gain	0.2900
11:95025893:CCAGA:C	acceptor_gain	0.2300
11:95026099:T:G	acceptor_gain	0.2300
11:95026315:A:T	donor_gain	0.2300
11:95025418:TCC:T	donor_gain	0.2200
11:95025892:ACCAG:A	acceptor_gain	0.2100
11:95027271:A:T	acceptor_gain	0.2100
11:95025985:A:C	acceptor_gain	0.2000

AlphaMissense

3341 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
11:95026119:T:A	W188R	0.989
11:95026119:T:C	W188R	0.989
11:95026431:T:C	F292L	0.988
11:95026433:T:A	F292L	0.988
11:95026433:T:G	F292L	0.988
11:95026002:T:A	W149R	0.983
11:95026002:T:C	W149R	0.983
11:95026359:T:C	F268L	0.983
11:95026361:C:A	F268L	0.983
11:95026361:C:G	F268L	0.983
11:95026395:T:C	F280L	0.983
11:95026397:C:A	F280L	0.983
11:95026397:C:G	F280L	0.983
11:95026113:T:C	F186L	0.982
11:95026115:T:A	F186L	0.982
11:95026115:T:G	F186L	0.982
11:95026360:T:C	F268S	0.982
11:95026371:T:C	F272L	0.981
11:95026373:T:A	F272L	0.981
11:95026373:T:G	F272L	0.981
11:95026282:A:T	K242I	0.980
11:95026412:C:A	N285K	0.979
11:95026412:C:G	N285K	0.979
11:95026269:T:C	F238L	0.975
11:95026271:C:A	F238L	0.975
11:95026271:C:G	F238L	0.975
11:95026446:T:A	W297R	0.973
11:95026446:T:C	W297R	0.973
11:95025630:T:C	F25L	0.971
11:95025632:T:A	F25L	0.971

dbSNP variants (sampled 300 via entrez): RS1002177445 (11:95027398 T>A,C), RS1002838076 (11:95025203 G>A,T), RS1005765574 (11:95026597 C>T), RS1006178330 (11:95023324 G>A), RS1006380281 (11:95027773 C>A,T), RS1006757658 (11:95028000 A>G), RS1007426611 (11:95025838 G>A,C), RS1008686827 (11:95024590 G>A), RS1009112862 (11:95024389 T>C), RS1011086903 (11:95026280 C>A,T), RS1012878168 (11:95024904 C>T), RS1013238538 (11:95025146 T>C), RS1013703013 (11:95027457 G>C,T), RS1014496035 (11:95024109 G>C), RS1014609078 (11:95024149 A>C,G)

Disease associations

OMIM: gene MIM:616581 | disease phenotypes:

GenCC curated gene-disease

Mondo (1): breast ductal adenocarcinoma (MONDO:0005590)

Orphanet (0):

HPO phenotypes

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

GWAS associations

1 associations (top):

Study	Trait	p-value
GCST010002_246	Refractive error	3.000000e-10

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D018270	Carcinoma, Ductal, Breast	C04.557.470.200.025.232.500; C04.557.470.615.132.500; C04.588.180.390; C17.800.090.500.390

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (1): CHEMBL1293226 (SINGLE PROTEIN)

Molecules with ChEMBL bioactivity

356 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 854,613 (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
CHEMBL1009	LEVODOPA	4	103,854
CHEMBL1014	CANDESARTAN CILEXETIL	4	11,194
CHEMBL1017	TELMISARTAN	4	27,457
CHEMBL103	PROGESTERONE	4	162,141
CHEMBL1051	LATANOPROST	4	14,975
CHEMBL1068	OXCARBAZEPINE	4	16,118
CHEMBL1070	NABUMETONE	4	55,063
CHEMBL1071	OXAPROZIN	4	51,044
CHEMBL1072	BUMETANIDE	4	22,087
CHEMBL1082	AMOXICILLIN	4	113,048
CHEMBL1082607	SALMETEROL XINAFOATE	4	15,201
CHEMBL1086	DIBUCAINE	4	17,231
CHEMBL1096	AMLEXANOX	4	4,195
CHEMBL1108	DROPERIDOL	4	16,888
CHEMBL1113	AMOXAPINE	4	20,128
CHEMBL1117	IDARUBICIN	4	136,065
CHEMBL1134	DECAMETHONIUM BROMIDE	4	1,096
CHEMBL11359	CISPLATIN	4
CHEMBL1148	TORSEMIDE	4	15,151
CHEMBL1169	AMINOSALICYLIC ACID	4	51,677
CHEMBL117785	TETRABENAZINE	4
CHEMBL1200323	LABETALOL HYDROCHLORIDE	4
CHEMBL1200330	PILOCARPINE HYDROCHLORIDE	4
CHEMBL1200332	PROTRIPTYLINE HYDROCHLORIDE	4
CHEMBL1200339	PHENYLEPHRINE HYDROCHLORIDE	4
CHEMBL1200347	ISOPROPAMIDE IODIDE	4
CHEMBL1200395	ORPHENADRINE CITRATE	4
CHEMBL1200399	BUSPIRONE HYDROCHLORIDE	4
CHEMBL1200418	DOBUTAMINE HYDROCHLORIDE	4
CHEMBL1200446	TRIPELENNAMINE HYDROCHLORIDE	4

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

GtoPdb / IUPHAR curated pharmacology

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

Target class: enzyme — 1.14.11.- Histone demethylases

Most potent curated ligand interactions (2 total), top 2:

Ligand	Action	Affinity	Parameter
ML324	Inhibition	6.04	pIC50
compound 6a [PMID: 18942826]	Inhibition	5.85	pIC50

Binding affinities (BindingDB)

10 measured of 22 human assays (25 total across all organisms); most potent 10 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value
(2E,4E,6R)-7-[4-(dimethylamino)phenyl]-N-hydroxy-4,6-dimethyl-7-oxohepta-2,4-dienamide	IC50	19 nM
2-[4-(methoxycarbonyl)pyridin-2-yl]pyridine-4-carboxylic acid	IC50	6600 nM
pyrimidine-4,6-dicarboxylic acid	IC50	27000 nM
N,3-dihydroxybenzamide	IC50	28000 nM
(2R)-2-(formamidoformic acid)-4-phenylbutanoic acid	IC50	100000 nM
pyridine-2,5-dicarboxylic acid	IC50	180000 nM
N,5-dihydroxy-2-methoxybenzamide	IC50	230000 nM
(2R)-2-(formamidoformic acid)-3-phenylpropanoic acid	IC50	320000 nM
N,5-dihydroxy-2-phenoxybenzamide	IC50	360000 nM
FUMARIC ACID	IC50	1.6e+06 nM

ChEMBL bioactivities

4164 potent at pChembl≥5 of 6100 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.60	Potency	2.5	nM	CHEMBL1544420
8.49	Potency	3.2	nM	CHEMBL1603504
8.49	Potency	3.2	nM	CHEMBL1374322
8.35	Potency	4.5	nM	CHEMBL1559324
8.35	Potency	4.5	nM	CHEMBL1372339
8.30	Potency	5	nM	CHEMBL1325370
8.30	Potency	5	nM	CHEMBL1308357
8.30	Potency	5	nM	CHEMBL1428808
8.25	Potency	5.6	nM	CHEMBL1606382
8.25	Potency	5.6	nM	CHEMBL1300305
8.25	Potency	5.6	nM	CHEMBL1300426
8.25	Potency	5.6	nM	CHEMBL1306372
8.25	Potency	5.6	nM	CHEMBL1550801
8.25	Potency	5.6	nM	CHEMBL1529649
8.25	Potency	5.6	nM	CHEMBL1496461
8.25	Potency	5.6	nM	CHEMBL1309552
8.20	Potency	6.3	nM	CHEMBL1449902
8.20	Potency	6.3	nM	CHEMBL1379448
8.15	Potency	7.1	nM	CHEMBL1520088
8.15	Potency	7.1	nM	CHEMBL1429549
8.10	Potency	7.9	nM	CHEMBL1571065
8.10	Potency	7.9	nM	CHEMBL1613442
8.05	Potency	8.9	nM	CHEMBL1490098
8.05	Potency	8.9	nM	CHEMBL1481013
8.00	Potency	10	nM	CHEMBL1438192
8.00	Potency	10	nM	CHEMBL1536921
8.00	Potency	10	nM	CHEMBL1323319
8.00	Potency	10	nM	CHEMBL1550078
8.00	Potency	10	nM	CHEMBL1569153
8.00	Potency	10	nM	CHEMBL1523905
7.95	Potency	11.2	nM	CHEMBL1332029
7.90	Potency	12.6	nM	CHEMBL1368170
7.80	Potency	15.8	nM	CHEMBL1443455
7.80	Potency	15.8	nM	CHEMBL1426405
7.70	Potency	20	nM	CHEMBL1454904
7.70	Potency	20	nM	CHEMBL1385656
7.65	Potency	22.4	nM	CHEMBL1321077
7.65	Potency	22.4	nM	CHEMBL1496496
7.60	Potency	25.1	nM	CHEMBL1359903
7.60	Potency	25.1	nM	CHEMBL1491066
7.60	Potency	25.1	nM	CHEMBL1338699
7.60	Potency	25.1	nM	CHEMBL1506727
7.55	Potency	28.2	nM	CHEMBL3194644
7.55	Potency	28.2	nM	CHEMBL1450827
7.55	Potency	28.2	nM	CHEMBL1379349
7.55	Potency	28.2	nM	CHEMBL1408342
7.50	Potency	31.6	nM	CHEMBL1439227
7.50	Potency	31.6	nM	CHEMBL1511162
7.45	Potency	35.5	nM	CHEMBL1541984
7.45	Potency	35.5	nM	CHEMBL1486209

PubChem BioAssay actives

77 with measured affinity, of 213 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
3-(benzylamino)pyridine-4-carboxylic acid	1282653: Inhibition of KDM4E (unknown origin) using H3K9Me3 peptide as substrate assessed as demethylation of substrate by Rapidfire mass spectrometric analysis	ic50	0.0398	uM
3-(furan-2-ylmethylamino)pyridine-4-carboxylic acid	1282653: Inhibition of KDM4E (unknown origin) using H3K9Me3 peptide as substrate assessed as demethylation of substrate by Rapidfire mass spectrometric analysis	ic50	0.0398	uM
3-[(3-methylthiophen-2-yl)methylamino]pyridine-4-carboxylic acid	1282653: Inhibition of KDM4E (unknown origin) using H3K9Me3 peptide as substrate assessed as demethylation of substrate by Rapidfire mass spectrometric analysis	ic50	0.0501	uM
2-[4-(2-phenylethylcarbamoyl)-2-pyridinyl]pyridine-4-carboxylic acid	1928202: Inhibition of KDM4E (unknown origin)	ic50	0.1100	uM
2-(4-chloro-3-hydroxyphenoxy)-3H-pyrido[3,4-d]pyrimidin-4-one	1281020: Inhibition of KDM4E (unknown origin) by RFMS assay	ic50	0.1259	uM
2-[5-[(4-chloro-2-methylphenyl)methoxy]pyrazol-1-yl]pyridine-4-carboxylic acid	1391739: Inhibition of KDM4E (unknown origin)	ic50	0.1600	uM
2-[4-(2-aminoethylcarbamoyl)-2-pyridinyl]pyridine-4-carboxylic acid	700433: Inhibition of JMJD2E catalytic domain by mass spectrophotometric analysis	ic50	0.1800	uM
4-hydrazinyl-4-oxobutanoic acid	1885263: Inhibition of human KDM4E heterogenously expressed in Escherichia coli using biotin-H3(1-15)K9Me3 as substrate and measured by Alphascreen assay	ic50	0.2000	uM
8-hydroxyquinoline-5-carboxylic acid	1289358: Inhibition of human N-terminal His6-tagged KDM4E catalytic domain (1 to 337 residues) expressed in Escherichia coli using ARK(me3)STGGK as substrate preincubated for 15 mins measured after 30 mins by FDH coupled enzyme assay	ic50	0.2000	uM
5-chloro-N-[(E)-[phenyl(pyridin-2-yl)methylidene]amino]pyridin-2-amine	1885285: Inhibition of N-terminal His6-tagged human KDM4E (1 to 337 residues) measured by ELISA assay	ic50	0.2900	uM
pyridine-2,4-dicarboxylic acid	2010693: Inhibition of his6-tagged human recombinant KDM4E using K9me3 as substrate by SPE-MS analysis	ic50	0.3000	uM
2-(1-cyclopentylpyrazol-4-yl)oxy-3H-pyrido[3,4-d]pyrimidin-4-one	1281020: Inhibition of KDM4E (unknown origin) by RFMS assay	ic50	0.3981	uM
2-[(6-propan-2-yl-3-pyridinyl)oxy]-3H-pyrido[3,4-d]pyrimidin-4-one	1281020: Inhibition of KDM4E (unknown origin) by RFMS assay	ic50	0.3981	uM
2-pyridin-2-ylpyridine-4-carboxylic acid	1249057: Inhibition of KDM4E (unknown origin) by alpha screen assay	ic50	0.3981	uM
4-(hydroxyamino)-4-oxobutanoic acid	698697: Inhibition of human KDM4E expressed in Escherichia coli using methyl lysine peptide substrate by AlphaScreen assay	ic50	0.4000	uM
2-[4-[[4-[(1S,2R)-2-aminocyclopropyl]phenyl]carbamoyl]-2-pyridinyl]pyridine-4-carboxylic acid;2,2,2-trifluoroacetic acid	1066183: Inhibition of recombinant JMJD2E (unknown origin) incubated for 15 mins prior to substrate addition by AlphaScreen method	ic50	0.4200	uM
2-(1-benzylpyrazol-4-yl)oxy-3H-pyrido[3,4-d]pyrimidin-4-one	1281020: Inhibition of KDM4E (unknown origin) by RFMS assay	ic50	0.5012	uM
2-[1-(cyclohexylmethyl)pyrazol-4-yl]oxy-3H-pyrido[3,4-d]pyrimidin-4-one	1281020: Inhibition of KDM4E (unknown origin) by RFMS assay	ic50	0.5012	uM
2-(1H-benzimidazol-2-yl)-5-methyl-4-phenyl-1H-pyrazol-3-one	1785092: Inhibition of N-terminal His6-tagged KDM4E (1 to 337 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3)-R3 preincubated for 10 mins followed by substrate addition by fluorescence based FDH-coupled assay	ic50	0.9000	uM
N-[3-(dimethylamino)propyl]-4-(8-hydroxyquinolin-6-yl)benzamide	1885289: Inhibition of KDM4E (unknown origin) measured by Alphascreen assay	ic50	0.9200	uM
3-(1-phenylethylamino)pyridine-2,4-dicarboxylic acid	2010691: Inhibition of human recombinant KDM4E using biotinylated-H3K9me3 peptide as substrate by SPE-MS analysis	ic50	0.9900	uM
3-aminopyridine-4-carboxylic acid	1281020: Inhibition of KDM4E (unknown origin) by RFMS assay	ic50	1.2589	uM
3-fluoropyridine-2,4-dicarboxylic acid	2010692: Inhibition of KDM4E (unknown origin) by SPE-MS analysis	ic50	1.3000	uM
5-fluoropyridine-2,4-dicarboxylic acid	2010692: Inhibition of KDM4E (unknown origin) by SPE-MS analysis	ic50	1.6000	uM
9-chloro-5-(4-hydroxyphenyl)-2,3,4,5-tetrahydro-1H-3-benzazepine-7,8-diol	604079: Non-competitive inhibition of JMJD2E relative to alpha-ketoglutarate	ki	1.9200	uM
(2S)-3-(3,4-dihydroxyphenyl)-2-hydrazinyl-2-methylpropanoic acid;hydrate	604078: Uncompetitive inhibition of JMJD2E relative to alpha-ketoglutarate	ki	1.9800	uM
3-[(1-methylpyrrolo[2,3-b]pyridin-3-yl)amino]pyridine-4-carboxylic acid	1934012: Inhibition of KDM4E (unknown origin ) incubated for 20 mins by Alphascreen assay	ic50	2.3000	uM
3-(benzylamino)pyridine-2,4-dicarboxylic acid	2010691: Inhibition of human recombinant KDM4E using biotinylated-H3K9me3 peptide as substrate by SPE-MS analysis	ic50	2.3600	uM
3-[(4-methoxyphenyl)methylamino]pyridine-2,4-dicarboxylic acid	2010691: Inhibition of human recombinant KDM4E using biotinylated-H3K9me3 peptide as substrate by SPE-MS analysis	ic50	2.4500	uM
3-(2-fluoroanilino)pyridine-2,4-dicarboxylic acid	700450: Inhibition of human JMJD2E	ic50	2.5000	uM
2,2-dimethyl-3,4-dihydrobenzo[h]chromene-5,6-dione	604082: Inhibition of JMJD2E	ic50	3.0000	uM
5,6,7-trihydroxy-2-phenylchromen-4-one	604082: Inhibition of JMJD2E	ic50	3.0000	uM
3,5,7-trihydroxy-2-(3,4,5-trihydroxyphenyl)chromen-4-one	604082: Inhibition of JMJD2E	ic50	3.0000	uM
5-(benzylamino)pyridine-2,4-dicarboxylic acid	2010698: Inhibition of N-terminal his6-tagged human recombinant KDM4E expressed in Escherichia coli using K9me3 as substrate by SPE-MS analysis	ic50	3.2000	uM
5-(cyclohexylmethylamino)pyridine-2,4-dicarboxylic acid	2010698: Inhibition of N-terminal his6-tagged human recombinant KDM4E expressed in Escherichia coli using K9me3 as substrate by SPE-MS analysis	ic50	3.2000	uM
N-[5-[4-[(1R,2S)-2-aminocyclopropyl]anilino]-5-oxopentyl]-8-hydroxyquinoline-5-carboxamide;hydrochloride	1066183: Inhibition of recombinant JMJD2E (unknown origin) incubated for 15 mins prior to substrate addition by AlphaScreen method	ic50	3.5000	uM
5-(4-phenylbutylamino)pyridine-2,4-dicarboxylic acid	2010698: Inhibition of N-terminal his6-tagged human recombinant KDM4E expressed in Escherichia coli using K9me3 as substrate by SPE-MS analysis	ic50	3.6000	uM
3-(1-phenylpropylamino)pyridine-2,4-dicarboxylic acid	2010691: Inhibition of human recombinant KDM4E using biotinylated-H3K9me3 peptide as substrate by SPE-MS analysis	ic50	3.6900	uM
N-[4-[(1S,2R)-2-aminocyclopropyl]phenyl]-8-hydroxyquinoline-5-carboxamide;hydrochloride	1066183: Inhibition of recombinant JMJD2E (unknown origin) incubated for 15 mins prior to substrate addition by AlphaScreen method	ic50	3.9000	uM
methyl 2-[2-(1H-benzimidazol-2-yl)-3-oxo-1H-pyrazol-5-yl]acetate	1885296: Inhibition of human KDM4E (1 to 378 residues) catalytic domain measured formaldehyde dehydrogenase (FDH)-coupled fluorescence assay	ic50	4.0000	uM
4-(2-methylhydrazinyl)-4-oxobutanoic acid	698697: Inhibition of human KDM4E expressed in Escherichia coli using methyl lysine peptide substrate by AlphaScreen assay	ic50	4.3000	uM
N,3-dihydroxybenzamide	604081: Inhibition of JMJD2E pre-incubated for 30 mins	ic50	4.8000	uM
N-[(5-chloro-8-hydroxyquinolin-7-yl)-(3-methylthiophen-2-yl)methyl]benzamide	1289329: Inhibition of KDM4E (unknown origin) preincubated for 15 mins followed by histone substrate addition measured after 1 hr by alphascreen assay	ic50	5.0000	uM
2-(1H-benzimidazol-2-yl)-5-methyl-4-prop-2-ynyl-1H-pyrazol-3-one	1785092: Inhibition of N-terminal His6-tagged KDM4E (1 to 337 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3)-R3 preincubated for 10 mins followed by substrate addition by fluorescence based FDH-coupled assay	ic50	5.0000	uM
2-(1H-benzimidazol-2-yl)-5-ethyl-4-phenyl-1H-pyrazol-3-one	1785092: Inhibition of N-terminal His6-tagged KDM4E (1 to 337 residues) (unknown origin) expressed in Escherichia coli BL21 (DE3)-R3 preincubated for 10 mins followed by substrate addition by fluorescence based FDH-coupled assay	ic50	5.0000	uM
2-(4-methoxycarbonyl-2-pyridinyl)pyridine-4-carboxylic acid	1066183: Inhibition of recombinant JMJD2E (unknown origin) incubated for 15 mins prior to substrate addition by AlphaScreen method	ic50	5.0000	uM
(2R)-3-[4-(4-fluorophenyl)sulfonyloxyphenyl]-2-(oxaloamino)propanoic acid	604080: Binding affinity to JMJD2E	ic50	5.0000	uM
(2R)-3-[4-(4-tert-butylphenyl)sulfonyloxyphenyl]-2-(oxaloamino)propanoic acid	604080: Binding affinity to JMJD2E	ic50	5.0000	uM
2-[1-(1-acetylazetidin-3-yl)triazol-4-yl]pyridine-4-carboxylic acid	1249057: Inhibition of KDM4E (unknown origin) by alpha screen assay	ic50	5.0119	uM
N-[6-[4-[(1R,2S)-2-aminocyclopropyl]anilino]-6-oxohexyl]-8-hydroxyquinoline-5-carboxamide;hydrochloride	1066183: Inhibition of recombinant JMJD2E (unknown origin) incubated for 15 mins prior to substrate addition by AlphaScreen method	ic50	5.1000	uM

CTD chemical–gene interactions

2 total (human), top 2 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
ML324	decreases reaction, affects binding	1
Aflatoxin B1	increases methylation	1

ChEMBL screening assays

67 unique, capped per target: 62 binding, 5 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1613914	Functional	PUBCHEM_BIOASSAY: qHTS Assay for Inhibitors of Human Jumonji Domain Containing 2E (JMJD2E). (Class of assay: confirmatory)	PubChem BioAssay data set
CHEMBL1798566	Binding	Uncompetitive inhibition of JMJD2E relative to alpha-ketoglutarate	Inhibitors of histone demethylases. — Bioorg Med Chem

Cellosaurus cell lines

5 cell lines: 5 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SU35	HAP1 KDM4E (-) 1	Cancer cell line	Male
CVCL_SU36	HAP1 KDM4E (-) 2	Cancer cell line	Male
CVCL_SU37	HAP1 KDM4E (-) 3	Cancer cell line	Male
CVCL_SU38	HAP1 KDM4E (-) 4	Cancer cell line	Male
CVCL_SU39	HAP1 KDM4E (-) 5	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT03414970	PHASE3	ACTIVE_NOT_RECRUITING	Hypofractionated Radiation Therapy After Mastectomy in Preventing Recurrence in Patients With Stage IIa-IIIa Breast Cancer
NCT00461344	PHASE2	TERMINATED	Docetaxel + Doxorubicin as Neoadjuvant Chemotherapy in Patients With Breast Cancer
NCT07499999	PHASE2	NOT_YET_RECRUITING	Randomized Double-Blind Phase II Trial of Baby Exemestane Versus Baby Tamoxifen in Post-Menopausal Women at High Risk for Breast Cancer
NCT00637364	PHASE1/PHASE2	SUSPENDED	High Intensity Focused Ultrasound Tumor Treatment for Pancreatic Cancer Pain
NCT02779855	PHASE1/PHASE2	COMPLETED	Talimogene Laherparepvec in Combination With Neoadjuvant Chemotherapy in Triple Negative Breast Cancer
NCT01753908	EARLY_PHASE1	COMPLETED	Broccoli Sprout Extract in Treating Patients With Breast Cancer
NCT01796041	EARLY_PHASE1	COMPLETED	Intraoperative Imaging of Breast Cancer With Indocyanine Green
NCT01208974	Not specified	ACTIVE_NOT_RECRUITING	Nipple-Areola Complex (NAC) Irradiation After Nipple-Sparing Mastectomy and Reconstruction
NCT01875198	Not specified	TERMINATED	Oncologic Impact of Splenectomy-omitting Radical Pancreatectomy in Well-selected Left-sided Pancreatic Cancer
NCT03543397	Not specified	UNKNOWN	MRI in Ductal Carcinoma in Situ (DCIS)
NCT03834532	Not specified	COMPLETED	Living Well After Breast Surgery