KDM4B

Summary

KDM4B (lysine demethylase 4B, HGNC:29136) is a protein-coding gene on chromosome 19p13.3, encoding Lysine-specific demethylase 4B (O94953). Histone demethylase that specifically demethylates ‘Lys-9’ of histone H3, thereby playing a role in histone code.

Enables histone H3K36 demethylase activity and histone H3K9me2/H3K9me3 demethylase activity. Predicted to be involved in brain development; chromatin remodeling; and regulation of gene expression. Located in cytosol and nucleoplasm. Implicated in autosomal dominant intellectual developmental disorder 65; breast cancer; colorectal cancer; malignant peripheral nerve sheath tumor; and stomach cancer. Biomarker of several diseases, including alopecia areata; lung cancer; medulloblastoma; prostate cancer; and stomach cancer.

Source: NCBI Gene 23030 — RefSeq curated summary.

At a glance

• Gene–disease (curated): intellectual developmental disorder, autosomal dominant 65 (Strong, ClinGen) — +2 more curated relationships
• GWAS associations: 21
• Clinical variants (ClinVar): 434 total — 9 pathogenic, 25 likely-pathogenic
• Phenotypes (HPO): 47
• Druggable target: yes — 5 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_015015

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:29136
Approved symbol	KDM4B
Name	lysine demethylase 4B
Location	19p13.3
Locus type	gene with protein product
Status	Approved
Aliases	KIAA0876, TDRD14B
Ensembl gene	ENSG00000127663
Ensembl biotype	protein_coding
OMIM	609765
Entrez	23030

Gene structure

Transcript identifiers

Ensembl transcripts: 28 — 22 protein_coding, 4 protein_coding_CDS_not_defined, 1 retained_intron, 1 TEC

ENST00000159111, ENST00000381759, ENST00000536461, ENST00000588166, ENST00000588337, ENST00000588361, ENST00000588961, ENST00000589104, ENST00000592159, ENST00000592175, ENST00000611640, ENST00000624683, ENST00000879848, ENST00000879849, ENST00000879850, ENST00000879851, ENST00000879852, ENST00000938251, ENST00000938252, ENST00000938253, ENST00000938254, ENST00000938255, ENST00000938256, ENST00000959316, ENST00000959317, ENST00000959318, ENST00000959319, ENST00000959320

RefSeq mRNA: 4 — MANE Select: NM_015015 NM_001370093, NM_001370094, NM_001411148, NM_015015

CCDS: CCDS12138, CCDS92493, CCDS92494

Canonical transcript exons

ENST00000159111 — 23 exons

Exon	Start	End
ENSE00000874796	5041137	5041251
ENSE00000874797	5032866	5033031
ENSE00001161414	5039836	5040011
ENSE00001407403	5016257	5016339
ENSE00003458712	5119653	5119852
ENSE00003480082	5071010	5071059
ENSE00003480305	5135339	5135561
ENSE00003515007	5137262	5137338
ENSE00003517411	5144248	5144412
ENSE00003526603	5143967	5144152
ENSE00003528065	5047476	5047669
ENSE00003547382	5144783	5144902
ENSE00003572103	5133883	5134061
ENSE00003577759	5082367	5082504
ENSE00003583467	5131076	5131545
ENSE00003634304	5131887	5132007
ENSE00003653116	5137621	5137676
ENSE00003654322	5137962	5138070
ENSE00003673603	5077367	5077470
ENSE00003673630	5150358	5150450
ENSE00003674720	5110622	5110818
ENSE00003727321	4969113	4969230
ENSE00003846002	5151335	5153598

Expression profiles

Bgee: expression breadth ubiquitous, 291 present calls, max score 95.66.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 40.8794 / max 522.8812, expressed in 1812 samples.

FANTOM5 promoters (5 alternative TSS)

Promoter ID	TPM avg	Samples expressed
173384	40.3044	1812
173389	0.4649	77
173387	0.0650	25
173390	0.0227	6
173388	0.0223	11

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
cervix squamous epithelium	UBERON:0006922	95.66	gold quality
dorsal motor nucleus of vagus nerve	UBERON:0002870	95.33	gold quality
corpus epididymis	UBERON:0004359	94.97	gold quality
blood	UBERON:0000178	94.54	gold quality
type B pancreatic cell	CL:0000169	94.12	gold quality
olfactory bulb	UBERON:0002264	93.66	gold quality
caput epididymis	UBERON:0004358	93.63	gold quality
inferior olivary complex	UBERON:0002127	93.23	gold quality
sural nerve	UBERON:0015488	93.20	gold quality
parotid gland	UBERON:0001831	93.04	gold quality
tendon of biceps brachii	UBERON:0008188	92.87	gold quality
nipple	UBERON:0002030	92.02	gold quality
skeletal muscle tissue of biceps brachii	UBERON:0004502	91.87	gold quality
cortical plate	UBERON:0005343	91.72	gold quality
epithelium of mammary gland	UBERON:0003244	91.70	gold quality
mammary duct	UBERON:0001765	91.67	gold quality
right lobe of thyroid gland	UBERON:0001119	91.52	gold quality
cauda epididymis	UBERON:0004360	91.40	gold quality
gingival epithelium	UBERON:0001949	91.38	gold quality
left lobe of thyroid gland	UBERON:0001120	91.35	gold quality
thyroid gland	UBERON:0002046	91.33	gold quality
bone marrow cell	CL:0002092	90.99	gold quality
prostate gland	UBERON:0002367	90.73	gold quality
placenta	UBERON:0001987	90.71	gold quality
amniotic fluid	UBERON:0000173	90.66	gold quality
endothelial cell	CL:0000115	90.25	gold quality
medial globus pallidus	UBERON:0002477	89.95	gold quality
seminal vesicle	UBERON:0000998	89.80	gold quality
Brodmann (1909) area 23	UBERON:0013554	89.79	gold quality
endocervix	UBERON:0000458	89.77	gold quality

Single-cell (SCXA)

Detected in 3 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	5.06
E-MTAB-7249	no	352.81
E-MTAB-6386	no	304.48

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

8 targets.

Target	Regulation
AR	Activation
BBC3	Unknown
CCNA1	Unknown
CCND1	Unknown
CDKN1A	Repression
ESR1	Unknown
TP53I3	Repression
WEE1	Unknown

Upstream regulators (CollecTRI, top): CEBPB, EPAS1, ESR1, HIF1A, TP53

miRNA regulators (miRDB)

78 targeting KDM4B, 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-3924	100.00	72.09	2394
HSA-MIR-29A-3P	100.00	73.11	1835
HSA-MIR-29B-3P	100.00	73.18	1833
HSA-MIR-29C-3P	100.00	73.15	1833
HSA-MIR-6833-3P	100.00	70.63	3197
HSA-MIR-4481	100.00	66.42	1669
HSA-MIR-4768-5P	100.00	69.49	2861
HSA-MIR-513A-5P	100.00	69.77	2465
HSA-MIR-5692B	100.00	71.32	2622
HSA-MIR-5692C	100.00	71.32	2622
HSA-MIR-196A-1-3P	99.99	72.15	2772
HSA-MIR-8068	99.98	73.85	2376
HSA-MIR-4745-5P	99.98	65.95	1028
HSA-MIR-27A-3P	99.98	72.13	2955
HSA-MIR-27B-3P	99.98	72.13	2955
HSA-MIR-9985	99.98	72.11	2939
HSA-MIR-9-3P	99.96	70.88	2068
HSA-MIR-4725-3P	99.96	69.53	2520
HSA-MIR-6780B-5P	99.96	69.60	2562
HSA-MIR-570-3P	99.96	72.41	4910
HSA-MIR-2110	99.96	66.68	1930
HSA-MIR-4760-3P	99.93	70.50	2385
HSA-MIR-338-5P	99.92	72.34	2951
HSA-MIR-6508-5P	99.92	70.67	2465
HSA-MIR-10527-5P	99.91	72.28	3754
HSA-MIR-3529-3P	99.90	73.55	3045
HSA-MIR-5682	99.89	72.56	1005
HSA-MIR-3140-3P	99.88	68.47	2069
HSA-MIR-4271	99.88	68.32	2244
HSA-MIR-7845-5P	99.88	64.88	771

Literature-anchored findings (GeneRIF, showing 40)

• Two GATA-binding sites within intron 6 of human JMJD2B gene were conserved in mouse Jmjd2b gene. (PMID:17611647)
• Results show that many genes regulated by hypoxia and HIF-1alpha show patterns of induction with JMJD (Jumonji-domain containing)1A and JMJD2B demonstrating robust, and JMJD2C more modest, up-regulation by hypoxia. (PMID:18713068)
• histone demethylases JMJD1A and JMJD2B are transcriptional targets of hypoxia-inducible factor HIF (PMID:18984585)
• Histone demethylase JMJD2B is regulated by both ERalpha and HIF-1alpha, drives breast cancer cell proliferation in normoxia and hypoxia, and epigenetically regulates the expression of cell cycle genes. (PMID:20682797)
• JMJD2B interacts with ERalpha and components of the SWI/SNF-B chromatin remodeling complex. JMJD2B is recruited to ERalpha target sites, demethylates H3K9me3 and facilitates transcription of ER responsive genes including MYB, MYC and CCND1. (PMID:21445275)
• knockdown of JMJD2B severely impairs estrogen-induced cell proliferation and the tumor formation capacity of breast cancer cells (PMID:21445275)
• Histone demethylase JMJD2B coordinates H3K4/H3K9 methylation and promotes hormonally responsive breast carcinogenesis. (PMID:21502505)
• High JMJD2B is associated with bladder and lung carcinogenesis through positive regulation of cyclin-dependent kinase 6. (PMID:21930796)
• JMJD2B is required for sustained proliferation and survival of tumor cells in vitro and in vivo, and its aberrant expression may contribute to the pathogenesis of gastric cancer. (PMID:22133676)
• showed that JMJD2B was overexpressed in colorectal cancer tissues and positively correlated with expression of the hypoxic marker carbonic anhydrase 9 (PMID:22745382)
• The histone demethylases KDM4B and KDM6B play critical roles in osteogenic commitment of mesenchymal stem/stromal cells. (PMID:22770241)
• JMJD2B may play a central role in gastric cancer cell growth and might constitute a novel therapeutic target to overcome hypoxia-induced radio-resistance, thereby improving the efficiency of radiation therapy. (PMID:23046878)
• Results suggest that by regulating JMJD2b and SUV39H1 expression, p53 not only controls transcription but also promotes HC relaxation to accelerate a rate-limiting step in the repair of complex genomes. (PMID:23376847)
• novel pathway by which Hsp90 activity alters the histone code via regulation of KDM4B stability. (PMID:23589305)
• A novel function of JMJD2B in promoting epithelial-mesenchymal transition and gastric cancer invasion and metastasis. (PMID:24077348)
• Jumonji domain-containing protein 2B has an essential role in cancer cell survival and tumor growth via DNA damage response mediation, which STAT3 partially regulates. (PMID:24473398)
• KDM4B was upregulated in colon and rectal adenocarcinomas and required for efficient growth and clonogenic activity of human HT-29 colon cancer cells. (PMID:24481461)
• Silencing of JMJD2B induces cell apoptosis via mitochondria-mediated and death receptor-mediated pathway activation in colorectal cancer. (PMID:24957706)
• results reveal that JMJD2B is dramatically upregulated in hepatocellular carcinoma, making it a potential diagnostic marker for the further development of HCC treatment therapies (PMID:25533242)
• JMJD2B and JMJD2C play an important role in the pathology of osteosarcoma via the up-regulation of FGF2. (PMID:25636512)
• Data indicate that miR-491-5p plays a tumor suppressor role in the development and progression of breast cancer via direct targeting the 3’UTR of JMJD2B mRNA. (PMID:25725194)
• Functional studies demonstrated that KDM4B regulates the Myc pathway. N-Myc was found to physically interact with and recruit KDM4B. KDM4B was found to regulate neuroblastoma cell proliferation and differentiation in vitro and xenograft growth in vivo. (PMID:25925418)
• High KDM4B expression is associated with endometrial cancer progression. (PMID:26397136)
• upon TGF-beta stimulation, KDM4B was recruited to the SOX9 promoter, removed the silencing H3K9me3 marks, and activated the transcription of SOX9. (PMID:26485430)
• KDM4B is a key mediator in epithelial-mesenchymal transition process, and may serve as an important prognostic marker and therapeutic target for the metastatic progression of human pancreatic cancer (PMID:26511091)
• KDM4B may play an important role in mitochondrial apoptosis and represent a potential therapeutic cancer target in colorectal cancer (PMID:27506941)
• KDM4B and KDM4D expression may associate with an aggressive subtype of classical Hodgkin lymphoma and be linked with radioresistance (PMID:27630312)
• The overall survival (OS) of the 50 JMJD2B-positive patients after surgery was significantly inferior to that of the JMJD2B-negative patients (five-year survival=56.7% vs. 92.6%; log-rank: p=0.01). Multivariate analysis showed that JMJD2B positivity was an independent prognostic factor. CONCLUSION: JMJD2B may be a novel prognostic factor for resected lung adenocarcinoma (PMID:27630338)
• This is the first demonstration that a Jumonji-domain histone demethylase regulates cellular processes required for peritoneal dissemination of cancer cells, one of the predominant factors affecting prognosis of EOC. The pathways regulated by KDM4B may present novel opportunities to develop combinatorial therapies to improve existing therapies for EOC patients. (PMID:27869162)
• identification of JMJD2B/KDM4B as a p53-inducible gene in response to DNA damage. (PMID:28073943)
• High KDM4B expression is associated with Neuroblastomas. (PMID:28684529)
• p-ERK-mediated phosphorylation and stabilization of JMJD2B during glucose deprivation contributes to its role in glucose uptake and cell viability, which may be modulated through epigenetically upregulation of GLUT1 in colon cancer cells. (PMID:28945223)
• findings illustrate the significance of CREB-KDM4B-STAT3 signaling cascade in DNA damage response, and highlight that KDM4B may potentially be a novel oncotarget for colorectal cancer radiotherapy. (PMID:29633065)
• our results provide novel insights into the pivotal role of JMJD2B in the development of hepatic steatosis through upregulation of PPARg2 and steatosis target genes. (PMID:30214048)
• These findings identify KDM4B as a therapeutic vulnerability in PTEN-deficient TNBC that otherwise would be resistant to PI3K inhibition. (PMID:30266800)
• the level of Fbxo22 in tumor tissues defines a new subclass of ER-positive breast cancers for which SCFFbxo22-mediated KDM4B degradation in patients can be a therapeutic target for the next generation of SERMs. (PMID:30418174)
• High KDM4B expression is associated with breast cancer. (PMID:30459150)
• activation of the DLX5/KDM4B signaling pathway might serve as an intrinsic mechanism that promotes tissue regeneration mediated by dental-derived mesenchymal stem cells. (PMID:30503866)
• These results reveal a novel function of KDM4B in controlling the JNK/c-Jun-induced IL-8-IL-8R axis in gastric cancer, and offer a new strategy in cancer therapy. (PMID:30683841)
• In this review, we discuss what is known about the regulation of KDM4B in response to the cellular environment, and how this context-dependent expression may be translated into specific biological consequences in cancer and reproductive biology (PMID:30759871)

Cross-species orthologs

5 orthologs

Organism	Symbol	Gene ID
danio_rerio	kdm4b	ENSDARG00000099675
mus_musculus	Kdm4b	ENSMUSG00000024201
rattus_norvegicus	Kdm4b	ENSRNOG00000049221
drosophila_melanogaster	Kdm5	FBGN0031759
caenorhabditis_elegans		WBGENE00004319

Paralogs (10): JARID2 (ENSG00000008083), KDM5D (ENSG00000012817), KDM4A (ENSG00000066135), KDM5A (ENSG00000073614), KDM4C (ENSG00000107077), KDM5B (ENSG00000117139), KDM5C (ENSG00000126012), KDM4D (ENSG00000186280), KDM4E (ENSG00000235268), KDM4F (ENSG00000255855)

Protein

Protein identifiers

Lysine-specific demethylase 4B — O94953 (reviewed: O94953)

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

All UniProt accessions (5): O94953, A0A0C4DFL8, F5GX28, K7EQ54, K7ES23

UniProt curated annotations — full annotation on UniProt →

Function. Histone demethylase that specifically demethylates ‘Lys-9’ of histone H3, thereby playing a role in histone code. Does not demethylate histone H3 ‘Lys-4’, H3 ‘Lys-27’, H3 ‘Lys-36’ nor H4 ‘Lys-20’. Only able to demethylate trimethylated H3 ‘Lys-9’, with a weaker activity than KDM4A, KDM4C and KDM4D. Demethylation of Lys residue generates formaldehyde and succinate. Plays a critical role in the development of the central nervous system (CNS).

Subcellular location. Nucleus.

Disease relevance. Intellectual developmental disorder, autosomal dominant 65 (MRD65) [MIM:619320] An autosomal dominant form of intellectual disability, a disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD65 is characterized by delayed motor and speech acquisition, variably impaired intellectual development, behavioral abnormalities, and dysmorphic facial features. Additional variable features include feeding difficulties, hypotonia, and seizures. The disease is caused by variants affecting the gene represented in this entry.

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

Domain organisation. The 2 Tudor domains recognize and bind methylated histones. Double Tudor domain has an interdigitated structure and the unusual fold is required for its ability to bind methylated histone tails.

Similarity. Belongs to the JHDM3 histone demethylase family.

Isoforms (2)

UniProt ID	Names	Canonical?
O94953-1	1	yes
O94953-2	2

RefSeq proteins (4): NP_001357022, NP_001357023, NP_001398077, NP_055830* (*=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
IPR047483	Tudor_KDM4B_rpt1	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 1.14.11.69 — [histone H3]-trimethyl-L-lysine36 demethylase (BRENDA: 7 organisms, 48 substrates, 42 inhibitors, 3 Km, 2 kcat entries)

Substrate kinetics (BRENDA)

11 substrates with measured Km, best-characterized 11. 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
[HISTONE H3]-N6,N6,N6-TRIMETHYL-L-LYSINE 36	0.32	1
[HISTONE H3]-N6,N6,N6-TRIMETHYLLYSINE36	0.32	1

Catalyzed reactions (Rhea), 1 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)

UniProt features (89 total): helix 23, strand 23, binding site 11, compositionally biased region 6, sequence variant 6, domain 4, region of interest 3, modified residue 3, zinc finger region 3, turn 3, splice variant 2, chain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

6 structures.

PDB	Method	Resolution (Å)
9H44	X-RAY DIFFRACTION	1.74
9T2D	X-RAY DIFFRACTION	1.8
4LXL	X-RAY DIFFRACTION	1.87
9T2H	X-RAY DIFFRACTION	1.99
4UC4	X-RAY DIFFRACTION	2.56
7JM5	X-RAY DIFFRACTION	2.7

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-O94953-F1	70.50	0.35

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

Post-translational modifications (3): 566, 602, 1065

Mutagenesis-validated functional residues (1):

Position	Phenotype
189–191	abolishes lysine-specific histone demethylase activity.

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-9018519	Estrogen-dependent gene expression
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-8939211	ESR-mediated signaling
R-HSA-9006931	Signaling by Nuclear Receptors

MSigDB gene sets: 310 (showing top): GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, MENSE_HYPOXIA_UP, GRAESSMANN_APOPTOSIS_BY_DOXORUBICIN_DN, BILD_SRC_ONCOGENIC_SIGNATURE, BOHN_PRIMARY_IMMUNODEFICIENCY_SYNDROM_DN, SHEDDEN_LUNG_CANCER_GOOD_SURVIVAL_A5, OSWALD_HEMATOPOIETIC_STEM_CELL_IN_COLLAGEN_GEL_UP, SMID_BREAST_CANCER_LUMINAL_B_UP, BILD_E2F3_ONCOGENIC_SIGNATURE, HIF1_Q3, GOBP_HEAD_DEVELOPMENT, NAKAMURA_TUMOR_ZONE_PERIPHERAL_VS_CENTRAL_DN, KIM_GASTRIC_CANCER_CHEMOSENSITIVITY, BASAKI_YBX1_TARGETS_DN, MARTINEZ_RESPONSE_TO_TRABECTEDIN_DN

GO Biological Process (4): chromatin remodeling (GO:0006338), brain development (GO:0007420), regulation of gene expression (GO:0010468), chromatin organization (GO:0006325)

GO Molecular Function (8): zinc ion binding (GO:0008270), histone demethylase activity (GO:0032452), histone H3K9 demethylase activity (GO:0032454), histone H3K36 demethylase activity (GO:0051864), histone H3K9me2/H3K9me3 demethylase activity (GO:0140684), oxidoreductase activity (GO:0016491), metal ion binding (GO:0046872), dioxygenase activity (GO:0051213)

GO Cellular Component (5): chromatin (GO:0000785), 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
ESR-mediated signaling	1
Chromatin organization	1
DNA Repair	1
DNA Double-Strand Break Repair	1
Signaling by Nuclear Receptors	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	3
histone H3 demethylase activity	2
2-oxoglutarate-dependent dioxygenase activity	2
chromatin organization	1
central nervous system development	1
animal organ development	1
head development	1
gene expression	1
regulation of macromolecule biosynthetic process	1
cellular component organization	1
transition metal ion binding	1
protein demethylase activity	1
histone modifying activity	1
histone H3K9 demethylase activity	1
catalytic activity	1
cation binding	1
oxidoreductase activity	1
chromosome	1
intracellular membrane-bounded organelle	1
nuclear lumen	1
chromosome, centromeric region	1
heterochromatin	1
cytoplasm	1

Protein interactions and networks

STRING

1404 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KDM4B	JMJD1C	Q15652	952
KDM4B	KDM3A	Q9Y4C1	836
KDM4B	KDM2B	Q8NHM5	769
KDM4B	SMARCA4	P51532	760
KDM4B	HIF1A	Q16665	745
KDM4B	KDM6B	O15054	734
KDM4B	KDM3B	Q7LBC6	714
KDM4B	ESR1	P03372	698
KDM4B	KDM1A	O60341	689
KDM4B	KDM2A	Q9Y2K7	641
KDM4B	KDM6A	O15550	634
KDM4B	DNMT1	P26358	629
KDM4B	SUV39H1	O43463	623
KDM4B	KDM7A	Q6ZMT4	621
KDM4B	CTNNB1	P35222	607

IntAct

23 interactions, top by confidence:

A	B	Type	Score
ZNF414	AHCYL1	psi-mi:“MI:0914”(association)	0.640
KDM4B		psi-mi:“MI:0871”(demethylation reaction)	0.440
KDM4B	H4C16	psi-mi:“MI:0407”(direct interaction)	0.440
H3-5	KDM4B	psi-mi:“MI:0915”(physical association)	0.370
GAMMAHV.ORF31	KDM4B	psi-mi:“MI:0915”(physical association)	0.370
CHORDC1	SSR3	psi-mi:“MI:0914”(association)	0.350
KDM4B	BAG2	psi-mi:“MI:0914”(association)	0.350
FKBP5	IFT56	psi-mi:“MI:0914”(association)	0.350
KDM4B	CCDC85C	psi-mi:“MI:0914”(association)	0.350
ZNF414	CASK	psi-mi:“MI:0914”(association)	0.350
FGFR1OP2	METTL15	psi-mi:“MI:0914”(association)	0.350
KDM4B	AP3B1	psi-mi:“MI:0914”(association)	0.350
ZNF414	KDM4B	psi-mi:“MI:0914”(association)	0.350
AFG2B	MMP24OS	psi-mi:“MI:0914”(association)	0.350
INSR	UBXN8	psi-mi:“MI:0914”(association)	0.350
INSR	ATOX1	psi-mi:“MI:0914”(association)	0.350
INSR	RIMOC1	psi-mi:“MI:0914”(association)	0.350
H2BC10	SMCHD1	psi-mi:“MI:2364”(proximity)	0.270
SPDYE4	SUPT5H	psi-mi:“MI:2364”(proximity)	0.270
SF1	KDM4B	psi-mi:“MI:0915”(physical association)	0.000
MED10	KDM4B	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (106): KDM4B (Affinity Capture-MS), DDX3X (Co-fractionation), KDM4B (Co-fractionation), KDM4B (Proximity Label-MS), KDM4B (Affinity Capture-MS), KDM4B (Affinity Capture-MS), KDM4A (Affinity Capture-MS), CCT3 (Affinity Capture-MS), CCT4 (Affinity Capture-MS), CCT6B (Affinity Capture-MS), CCT2 (Affinity Capture-MS), CCT7 (Affinity Capture-MS), CCDC85C (Affinity Capture-MS), CCT5 (Affinity Capture-MS), TCP1 (Affinity Capture-MS)

ESM2 similar proteins: A0A0P0VUY4, A1YVX4, A3KMI0, A7E320, B6CHA3, B9G8P1, C0SQ89, E7EZF3, F4IGL2, F6UA42, J9VI03, O49139, O75164, O94953, O97159, P0CB22, P26358, P34305, Q0E0Q3, Q23541, Q24K09, Q5F3R2, Q5RD88, Q5RDX4, Q60EX7, Q61T02, Q651Z7, Q6C710, Q6K431, Q7TMI3, Q7TPK1, Q8BW72, Q8LMR2, Q8LPU5, Q8VCD7, Q8VDF2, Q8VXV7, Q8VYB9, Q91VY5, Q92072

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

19 interactions.

A	Effect	B	Mechanism
KDM4B	“up-regulates quantity by expression”	AR	“transcriptional regulation”
TP53	“up-regulates quantity by expression”	KDM4B	“transcriptional regulation”
KDM4B	“down-regulates quantity by repression”	CDKN1A	“transcriptional regulation”
KDM4B	“down-regulates quantity by repression”	TP53I3	“transcriptional regulation”
KDM4B	“down-regulates quantity by repression”	BBC3	“transcriptional regulation”
KDM4B	“down-regulates activity”	H3C1	demethylation
Hypoxia	up-regulates	KDM4B
DNA_damage	up-regulates	KDM4B
ESR1	“up-regulates quantity by expression”	KDM4B	“transcriptional regulation”
HIF1A	“up-regulates quantity by expression”	KDM4B	“transcriptional regulation”
KDM4B	“down-regulates activity”	“Histone H3”	demethylation
EPAS1	“up-regulates quantity by expression”	KDM4B	“transcriptional regulation”
MAPK1	“up-regulates quantity by stabilization”	KDM4B	phosphorylation
2-oxoglutarate(2-)	“up-regulates activity”	KDM4B	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	9
Likely pathogenic	25
Uncertain significance	280
Likely benign	68
Benign	12

Top pathogenic / likely-pathogenic (30)

Variant ID	HGVS	Classification
1098738	NM_015015.3(KDM4B):c.659T>C (p.Leu220Pro)	Pathogenic
1098739	NM_015015.3(KDM4B):c.2221dup (p.Glu741fs)	Pathogenic
1098740	NM_015015.3(KDM4B):c.1778_1779del (p.Glu593fs)	Pathogenic
1802611	NM_015015.3(KDM4B):c.1783C>T (p.Gln595Ter)	Pathogenic
3603009	NM_015015.3(KDM4B):c.398A>G (p.Tyr133Cys)	Pathogenic
4072464	NM_015015.3(KDM4B):c.2269_2270del (p.Leu757fs)	Pathogenic
4077218	NM_015015.3(KDM4B):c.432+1del	Pathogenic
4091240	NM_015015.3(KDM4B):c.3005_3006insA (p.Ser1003fs)	Pathogenic
4622786	NM_015015.3(KDM4B):c.2407C>T (p.Arg803Ter)	Pathogenic
1312409	NM_015015.3(KDM4B):c.432+2dup	Likely pathogenic
1329940	NM_015015.3(KDM4B):c.2441+1G>A	Likely pathogenic
1679582	NM_015015.3(KDM4B):c.2440_2441+1del	Likely pathogenic
1700101	NM_015015.3(KDM4B):c.1857del (p.Thr620fs)	Likely pathogenic
1701834	NM_015015.3(KDM4B):c.1135C>T (p.Gln379Ter)	Likely pathogenic
1804113	NM_015015.3(KDM4B):c.1198_1222del (p.Ala399_Leu400insTer)	Likely pathogenic
1992399	NM_015015.3(KDM4B):c.2935G>T (p.Glu979Ter)	Likely pathogenic
2428732	NM_015015.3(KDM4B):c.2661_2677del (p.Val888fs)	Likely pathogenic
2429016	NM_015015.3(KDM4B):c.2343dup (p.Gly782fs)	Likely pathogenic
2576583	NM_015015.3(KDM4B):c.1316-1G>A	Likely pathogenic
2664875	NM_015015.3(KDM4B):c.2550+2T>C	Likely pathogenic
3062355	NM_015015.3(KDM4B):c.994_998del (p.Leu332fs)	Likely pathogenic
3068476	NM_015015.3(KDM4B):c.1217del (p.Gly406fs)	Likely pathogenic
3252680	NM_015015.3(KDM4B):c.432+1G>C	Likely pathogenic
3777114	NM_015015.3(KDM4B):c.2085+2del	Likely pathogenic
3779785	NM_015015.3(KDM4B):c.2901+59_2901+60insTCCCGAGAGCATCACGGTGAGCTGTGGGGTGGGGCAGGGGGCGGGGGGAGGCTGGGAGCACAGCGACAACCTGTA	Likely pathogenic
3900791	NM_015015.3(KDM4B):c.2954T>C (p.Leu985Pro)	Likely pathogenic
4056537	NM_015015.3(KDM4B):c.2329G>T (p.Glu777Ter)	Likely pathogenic
4081468	NM_015015.3(KDM4B):c.2442-5_2445delinsGC	Likely pathogenic
4293019	NM_015015.3(KDM4B):c.1980G>A (p.Trp660Ter)	Likely pathogenic
4293073	NM_015015.3(KDM4B):c.1771del (p.Ala591fs)	Likely pathogenic

SpliceAI

7980 predictions. Top by Δscore:

Variant	Effect	Δscore
19:4969228:CAGG:C	donor_loss	1.0000
19:4969230:GGT:G	donor_loss	1.0000
19:4969231:GTG:G	donor_loss	1.0000
19:4976549:G:GT	donor_gain	1.0000
19:5016251:TTTTA:T	acceptor_loss	1.0000
19:5016252:TTTA:T	acceptor_loss	1.0000
19:5016253:TTA:T	acceptor_loss	1.0000
19:5016254:TAGG:T	acceptor_loss	1.0000
19:5016255:A:AG	acceptor_gain	1.0000
19:5016255:AG:A	acceptor_gain	1.0000
19:5016256:G:GC	acceptor_loss	1.0000
19:5016256:G:GG	acceptor_gain	1.0000
19:5016256:GG:G	acceptor_gain	1.0000
19:5016256:GGA:G	acceptor_gain	1.0000
19:5016337:GAA:G	donor_gain	1.0000
19:5016338:AA:A	donor_gain	1.0000
19:5016338:AAG:A	donor_loss	1.0000
19:5016339:AGTA:A	donor_loss	1.0000
19:5016340:G:GG	donor_gain	1.0000
19:5016340:G:T	donor_loss	1.0000
19:5016341:T:G	donor_loss	1.0000
19:5032861:CACA:C	acceptor_loss	1.0000
19:5032863:CA:C	acceptor_loss	1.0000
19:5032865:G:C	acceptor_loss	1.0000
19:5032865:GGT:G	acceptor_gain	1.0000
19:5032865:GGTGT:G	acceptor_gain	1.0000
19:5033005:G:GT	donor_gain	1.0000
19:5039831:TGCA:T	acceptor_loss	1.0000
19:5039832:GCA:G	acceptor_loss	1.0000
19:5039833:CA:C	acceptor_loss	1.0000

AlphaMissense

7161 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:5032942:T:C	F18L	1.000
19:5032943:T:C	F18S	1.000
19:5032944:T:A	F18L	1.000
19:5032944:T:G	F18L	1.000
19:5032948:C:T	P20S	1.000
19:5032949:C:A	P20Q	1.000
19:5032949:C:G	P20R	1.000
19:5032964:T:C	F25S	1.000
19:5032981:T:G	Y31D	1.000
19:5033027:C:A	A46D	1.000
19:5039843:C:A	P50H	1.000
19:5039843:C:G	P50R	1.000
19:5039854:T:A	W54R	1.000
19:5039854:T:C	W54R	1.000
19:5039855:G:C	W54S	1.000
19:5039856:G:C	W54C	1.000
19:5039856:G:T	W54C	1.000
19:5039897:T:A	I68N	1.000
19:5039897:T:G	I68S	1.000
19:5039941:T:C	F83L	1.000
19:5039942:T:C	F83S	1.000
19:5039943:C:A	F83L	1.000
19:5039943:C:G	F83L	1.000
19:5039955:T:A	N87K	1.000
19:5039955:T:G	N87K	1.000
19:5039990:G:C	R99P	1.000
19:5041172:T:C	L118P	1.000
19:5041178:G:C	R120P	1.000
19:5041186:T:A	W123R	1.000
19:5041186:T:C	W123R	1.000

dbSNP variants (sampled 300 via entrez): RS1000005316 (19:5005904 G>A), RS1000048463 (19:5102163 C>T), RS1000073382 (19:5093696 G>A,C), RS1000080693 (19:5040840 CAA>C), RS1000155721 (19:5148544 C>T), RS1000157900 (19:5070713 G>A,T), RS1000166644 (19:5133799 A>G), RS1000170199 (19:5004472 G>A), RS1000175298 (19:5091649 A>G), RS1000184619 (19:5127368 C>T), RS1000209271 (19:5074035 G>T), RS1000216475 (19:5077190 C>G,T), RS1000229053 (19:5091487 G>A,C), RS1000243383 (19:5079763 C>T), RS1000267207 (19:5066490 G>A,C)

Disease associations

OMIM: gene MIM:609765 | disease phenotypes: MIM:619320

GenCC curated gene-disease

Disease	Classification	Inheritance
intellectual developmental disorder, autosomal dominant 65	Strong	Autosomal dominant
complex neurodevelopmental disorder	Strong	Autosomal dominant
syndromic intellectual disability	Supportive	Autosomal dominant

ClinGen Gene-Disease Validity (1)

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

Disease	Classification	Inheritance
intellectual developmental disorder, autosomal dominant 65	Strong	AD

Mondo (4): intellectual developmental disorder, autosomal dominant 65 (MONDO:0023657), neurodevelopmental disorder (MONDO:0700092), complex neurodevelopmental disorder (MONDO:0100038), syndromic intellectual disability (MONDO:0000508)

Orphanet (0):

HPO phenotypes

47 total (30 of 47 shown, HPO-id order):

HPO	Term
HP:0000006	Autosomal dominant inheritance
HP:0000215	Thick upper lip vermilion
HP:0000262	Turricephaly
HP:0000297	Facial hypotonia
HP:0000311	Round face
HP:0000322	Short philtrum
HP:0000324	Facial asymmetry
HP:0000341	Narrow forehead
HP:0000343	Long philtrum
HP:0000347	Micrognathia
HP:0000358	Posteriorly rotated ears
HP:0000369	Low-set ears
HP:0000400	Macrotia
HP:0000414	Bulbous nose
HP:0000431	Wide nasal bridge
HP:0000463	Anteverted nares
HP:0000582	Upslanted palpebral fissure
HP:0000664	Synophrys
HP:0000718	Aggressive behavior
HP:0000722	Compulsive behaviors
HP:0000729	Autistic behavior
HP:0000750	Delayed speech and language development
HP:0000954	Single transverse palmar crease
HP:0001249	Intellectual disability
HP:0001250	Seizure
HP:0001251	Ataxia
HP:0001252	Hypotonia
HP:0001263	Global developmental delay
HP:0001274	Agenesis of corpus callosum
HP:0001773	Short foot

GWAS associations

21 associations (top):

Study	Trait	p-value
GCST002126_17	Periodontitis (CDC/AAP)	6.000000e-06
GCST002126_5	Periodontitis (CDC/AAP)	6.000000e-06
GCST004608_130	Granulocyte percentage of myeloid white cells	1.000000e-12
GCST004609_92	Monocyte percentage of white cells	3.000000e-09
GCST004632_15	Lymphocyte percentage of white cells	1.000000e-11
GCST004633_8	Neutrophil percentage of white cells	6.000000e-12
GCST005752_110	Systemic lupus erythematosus	1.000000e-06
GCST006624_100	Systolic blood pressure	9.000000e-22
GCST007269_173	Pulse pressure	1.000000e-10
GCST008971_149	Urate levels	2.000000e-12
GCST010244_139	Triglyceride levels	9.000000e-13
GCST011122_12	Walking pace	4.000000e-08
GCST012227_687	Hip circumference adjusted for BMI	3.000000e-10
GCST90002388_32	Lymphocyte count	6.000000e-11
GCST90002389_259	Lymphocyte percentage of white cells	4.000000e-23
GCST90002393_635	Monocyte count	4.000000e-11
GCST90002394_433	Monocyte percentage of white cells	4.000000e-21
GCST90002397_177	Mean spheric corpuscular volume	1.000000e-11
GCST90002398_77	Neutrophil count	9.000000e-15
GCST90002399_216	Neutrophil percentage of white cells	1.000000e-27
GCST90020028_1646	Hip circumference adjusted for BMI	1.000000e-09

EFO canonical traits (12, from GWAS)

EFO ID	Trait name
EFO:0007997	granulocyte percentage of myeloid white cells
EFO:0007989	monocyte percentage of leukocytes
EFO:0007993	lymphocyte percentage of leukocytes
EFO:0007990	neutrophil percentage of leukocytes
EFO:0006335	systolic blood pressure
EFO:0005763	pulse pressure measurement
EFO:0004531	urate measurement
EFO:0004530	triglyceride measurement
EFO:0008039	BMI-adjusted hip circumference
EFO:0004587	lymphocyte count
EFO:0005091	monocyte count
EFO:0004833	neutrophil count

MeSH disease descriptors (1)

Descriptor	Name	Tree numbers
D065886	Neurodevelopmental Disorders	F03.625

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (3): CHEMBL3313832 (SINGLE PROTEIN), CHEMBL3430889 (PROTEIN COMPLEX), CHEMBL6195532 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

5 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 49,888 (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
CHEMBL1413	CICLOPIROX	4	14,782
CHEMBL109480	TANESPIMYCIN	3	3,645
CHEMBL278315	GELDANAMYCIN	2	30,673
CHEMBL383824	ALVESPIMYCIN	2	752
CHEMBL5314494	ZAVONDEMSTAT	2	36

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

ChEMBL bioactivities

140 potent at pChembl≥5 of 152 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
8.40	IC50	4	nM	CHEMBL4438830
8.30	IC50	5	nM	CHEMBL4449500
8.22	IC50	6	nM	CHEMBL4438830
8.10	IC50	8	nM	CHEMBL4438830
8.10	IC50	8	nM	CHEMBL4449500
8.00	IC50	10	nM	CHEMBL3785491
7.92	IC50	12	nM	CHEMBL4438830
7.92	IC50	12	nM	CHEMBL4449500
7.82	IC50	15	nM	CHEMBL4440395
7.77	IC50	17	nM	CHEMBL3775894
7.75	IC50	18	nM	CHEMBL4466130
7.72	IC50	19	nM	CHEMBL4592908
7.70	IC50	20	nM	CHEMBL4590283
7.70	IC50	20	nM	CHEMBL4585876
7.68	IC50	21	nM	CHEMBL4438830
7.66	IC50	22	nM	CHEMBL4449500
7.62	IC50	24	nM	CHEMBL4559561
7.57	IC50	27	nM	CHEMBL4567766
7.54	IC50	29	nM	CHEMBL3775668
7.54	IC50	29	nM	CHEMBL4573390
7.51	IC50	31	nM	CHEMBL3774537
7.50	IC50	32	nM	CHEMBL4438034
7.50	IC50	32	nM	CHEMBL4447515
7.48	IC50	33	nM	CHEMBL4516101
7.48	IC50	33	nM	CHEMBL4561958
7.48	IC50	33	nM	CHEMBL5203308
7.48	IC50	33	nM	CHEMBL6067729
7.46	IC50	35	nM	CHEMBL4216044
7.44	IC50	36	nM	CHEMBL3775121
7.44	IC50	36	nM	CHEMBL4449500
7.44	IC50	36	nM	CHEMBL4438830
7.41	IC50	39	nM	CHEMBL3775545
7.41	IC50	39	nM	CHEMBL3775548
7.40	IC50	40	nM	CHEMBL4525269
7.39	IC50	41	nM	CHEMBL3774456
7.37	IC50	43	nM	CHEMBL4449500
7.35	IC50	45	nM	CHEMBL4435185
7.33	IC50	47	nM	CHEMBL4558689
7.31	IC50	49	nM	CHEMBL4520178
7.30	IC50	50	nM	CHEMBL3775899
7.26	IC50	55	nM	CHEMBL3775277
7.25	IC50	56	nM	CHEMBL4216044
7.24	IC50	57	nM	CHEMBL4464471
7.24	IC50	58	nM	ZAVONDEMSTAT
7.21	IC50	62	nM	CHEMBL3775516
7.21	IC50	61	nM	CHEMBL3775953
7.21	IC50	62	nM	CHEMBL4449500
7.21	IC50	62	nM	CHEMBL4438830
7.20	IC50	63	nM	CHEMBL4549505
7.18	IC50	66	nM	CHEMBL4525269

PubChem BioAssay actives

142 with measured affinity, of 188 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	1556121: Inhibition of full length human KDM4B assessed as decrease in demethylation of substrate using peptide (ARTKQTARK(Me3)STGGKAPRKQLA-GGKbiotin) as substrate and 0.25 uM 2OG as cosubstrate pre-incubated for 10 mins before substrate addition followed by centrifugation for 1 min and measured after 15 mins by AlphaScreen assay	ic50	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	1556121: Inhibition of full length human KDM4B assessed as decrease in demethylation of substrate using peptide (ARTKQTARK(Me3)STGGKAPRKQLA-GGKbiotin) as substrate and 0.25 uM 2OG as cosubstrate pre-incubated for 10 mins before substrate addition followed by centrifugation for 1 min and measured after 15 mins by AlphaScreen assay	ic50	0.0050	uM
3-(8-hydroxyquinolin-6-yl)-N-(3-phenylpropyl)benzamide	1289369: Inhibition of human N-terminal GST-tagged KDM4B (1 to 500 residues) expressed in baculovirus infected sf9 cells using H3K4me3 as substrate	ic50	0.0100	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	1556102: Inhibition of N-terminal GST-tagged recombinant human KDM4B (1 to 500 residues) expressed in baculovirus infected Sf9 insect cells 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	0.0150	uM
8-[4-[2-[4-(3,5-dichlorophenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282543: Inhibition of recombinant human N-terminal GST-tagged KDM4B (1 to 500 residues) expressed in baculovirus infected sf9 cells using biotin-H3K9me3 as substrate preincubated for 10 mins measured after 20 mins by alphascreen assay	ic50	0.0170	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	1556102: Inhibition of N-terminal GST-tagged recombinant human KDM4B (1 to 500 residues) expressed in baculovirus infected Sf9 insect cells 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	0.0180	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	1556102: Inhibition of N-terminal GST-tagged recombinant human KDM4B (1 to 500 residues) expressed in baculovirus infected Sf9 insect cells 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	0.0190	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	1556102: Inhibition of N-terminal GST-tagged recombinant human KDM4B (1 to 500 residues) expressed in baculovirus infected Sf9 insect cells 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	0.0200	uM
8-[4-[2-[4-(4-pyridin-4-ylphenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556102: Inhibition of N-terminal GST-tagged recombinant human KDM4B (1 to 500 residues) expressed in baculovirus infected Sf9 insect cells 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	0.0200	uM
8-[4-[2-[4-(4-pyridin-3-ylphenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556102: Inhibition of N-terminal GST-tagged recombinant human KDM4B (1 to 500 residues) expressed in baculovirus infected Sf9 insect cells 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	0.0240	uM
8-[4-[2-[4-(3-pyridin-3-ylphenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556102: Inhibition of N-terminal GST-tagged recombinant human KDM4B (1 to 500 residues) expressed in baculovirus infected Sf9 insect cells 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	0.0270	uM
8-[4-[2-(4-thiophen-2-ylpiperidin-1-yl)ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282543: Inhibition of recombinant human N-terminal GST-tagged KDM4B (1 to 500 residues) expressed in baculovirus infected sf9 cells using biotin-H3K9me3 as substrate preincubated for 10 mins measured after 20 mins by alphascreen assay	ic50	0.0290	uM
8-[4-[2-[4-(3-chlorophenyl)-4-methylpiperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556102: Inhibition of N-terminal GST-tagged recombinant human KDM4B (1 to 500 residues) expressed in baculovirus infected Sf9 insect cells 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	0.0290	uM
8-[4-[2-[4-(3-chlorophenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282543: Inhibition of recombinant human N-terminal GST-tagged KDM4B (1 to 500 residues) expressed in baculovirus infected sf9 cells using biotin-H3K9me3 as substrate preincubated for 10 mins measured after 20 mins by alphascreen assay	ic50	0.0310	uM
8-[4-[2-[4-(4-pyrimidin-5-ylphenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556102: Inhibition of N-terminal GST-tagged recombinant human KDM4B (1 to 500 residues) expressed in baculovirus infected Sf9 insect cells 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	0.0320	uM
8-[4-[2-[4-(3-fluorophenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556102: Inhibition of N-terminal GST-tagged recombinant human KDM4B (1 to 500 residues) expressed in baculovirus infected Sf9 insect cells 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	0.0320	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	1556102: Inhibition of N-terminal GST-tagged recombinant human KDM4B (1 to 500 residues) expressed in baculovirus infected Sf9 insect cells 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	0.0330	uM
8-[4-[2-[4-(3-pyridin-2-ylphenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556102: Inhibition of N-terminal GST-tagged recombinant human KDM4B (1 to 500 residues) expressed in baculovirus infected Sf9 insect cells 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	0.0330	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	1885314: Inhibition of KDM4B (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	1885274: Inhibition of KDM4B (unknown origin) using H3K9me3 as substrate and measured by LANCE TR-FRET assay	ic50	0.0350	uM
8-[4-[2-[4-(2,4-difluorophenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282543: Inhibition of recombinant human N-terminal GST-tagged KDM4B (1 to 500 residues) expressed in baculovirus infected sf9 cells using biotin-H3K9me3 as substrate preincubated for 10 mins measured after 20 mins by alphascreen assay	ic50	0.0360	uM
8-[4-[2-[4-[3-(trifluoromethyl)phenyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282543: Inhibition of recombinant human N-terminal GST-tagged KDM4B (1 to 500 residues) expressed in baculovirus infected sf9 cells using biotin-H3K9me3 as substrate preincubated for 10 mins measured after 20 mins by alphascreen assay	ic50	0.0390	uM
8-[4-[2-[4-(4-methoxyphenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282543: Inhibition of recombinant human N-terminal GST-tagged KDM4B (1 to 500 residues) expressed in baculovirus infected sf9 cells using biotin-H3K9me3 as substrate preincubated for 10 mins measured after 20 mins by alphascreen assay	ic50	0.0390	uM
8-[4-[1-(cyclobutylmethyl)piperidin-4-yl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556122: Inhibition of full length human KDM4B assessed as decrease in demethylation of substrate using peptide (ARTKQTARK(Me3)STGGKAPRKQLA-GGKbiotin) as substrate and 0.5 uM 2OG as cosubstrate pre-incubated for 10 mins before substrate addition followed by centrifugation for 1 min and measured after 15 mins by AlphaScreen assay	ic50	0.0400	uM
8-[4-[2-[4-(3,5-difluorophenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282543: Inhibition of recombinant human N-terminal GST-tagged KDM4B (1 to 500 residues) expressed in baculovirus infected sf9 cells using biotin-H3K9me3 as substrate preincubated for 10 mins measured after 20 mins by alphascreen assay	ic50	0.0410	uM
8-[4-[2-(4,7-dimethylspiro[1,2-dihydroindene-3,4’-piperidine]-1’-yl)ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556102: Inhibition of N-terminal GST-tagged recombinant human KDM4B (1 to 500 residues) expressed in baculovirus infected Sf9 insect cells 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	0.0450	uM
8-[4-[2-[4-(3-pyrimidin-5-ylphenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556102: Inhibition of N-terminal GST-tagged recombinant human KDM4B (1 to 500 residues) expressed in baculovirus infected Sf9 insect cells 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	0.0470	uM
8-[4-[2-[4-(3-tert-butylphenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556102: Inhibition of N-terminal GST-tagged recombinant human KDM4B (1 to 500 residues) expressed in baculovirus infected Sf9 insect cells 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	0.0490	uM
8-[4-[2-[4-[(4-chlorophenyl)methyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282543: Inhibition of recombinant human N-terminal GST-tagged KDM4B (1 to 500 residues) expressed in baculovirus infected sf9 cells using biotin-H3K9me3 as substrate preincubated for 10 mins measured after 20 mins by alphascreen assay	ic50	0.0500	uM
8-[4-[2-(4-pyridin-4-ylpiperidin-1-yl)ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282543: Inhibition of recombinant human N-terminal GST-tagged KDM4B (1 to 500 residues) expressed in baculovirus infected sf9 cells using biotin-H3K9me3 as substrate preincubated for 10 mins measured after 20 mins by alphascreen assay	ic50	0.0550	uM
8-[4-(2-spiro[1H-2-benzofuran-3,4’-piperidine]-1’-ylethyl)pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556102: Inhibition of N-terminal GST-tagged recombinant human KDM4B (1 to 500 residues) expressed in baculovirus infected Sf9 insect cells 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	0.0570	uM
8-[4-[2-[4-(4-fluorophenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282543: Inhibition of recombinant human N-terminal GST-tagged KDM4B (1 to 500 residues) expressed in baculovirus infected sf9 cells using biotin-H3K9me3 as substrate preincubated for 10 mins measured after 20 mins by alphascreen assay	ic50	0.0610	uM
8-[4-[2-[4-[[4-(trifluoromethyl)phenyl]methyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282543: Inhibition of recombinant human N-terminal GST-tagged KDM4B (1 to 500 residues) expressed in baculovirus infected sf9 cells using biotin-H3K9me3 as substrate preincubated for 10 mins measured after 20 mins by alphascreen assay	ic50	0.0620	uM
8-[4-[2-[4-[3-(morpholin-4-ylmethyl)phenyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556102: Inhibition of N-terminal GST-tagged recombinant human KDM4B (1 to 500 residues) expressed in baculovirus infected Sf9 insect cells 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	0.0630	uM
8-[4-[2-[4-(3-methoxyphenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556102: Inhibition of N-terminal GST-tagged recombinant human KDM4B (1 to 500 residues) expressed in baculovirus infected Sf9 insect cells 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	0.0670	uM
8-[4-[2-[4-[(3,4-dichlorophenyl)methyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282543: Inhibition of recombinant human N-terminal GST-tagged KDM4B (1 to 500 residues) expressed in baculovirus infected sf9 cells using biotin-H3K9me3 as substrate preincubated for 10 mins measured after 20 mins by alphascreen assay	ic50	0.0680	uM
8-[4-[2-[4-(4-methylsulfonylphenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282543: Inhibition of recombinant human N-terminal GST-tagged KDM4B (1 to 500 residues) expressed in baculovirus infected sf9 cells using biotin-H3K9me3 as substrate preincubated for 10 mins measured after 20 mins by alphascreen assay	ic50	0.0690	uM
4-[1-[2-[1-(4-oxo-3H-pyrido[3,4-d]pyrimidin-8-yl)pyrazol-4-yl]ethyl]piperidin-4-yl]benzonitrile	1282543: Inhibition of recombinant human N-terminal GST-tagged KDM4B (1 to 500 residues) expressed in baculovirus infected sf9 cells using biotin-H3K9me3 as substrate preincubated for 10 mins measured after 20 mins by alphascreen assay	ic50	0.0690	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	1282543: Inhibition of recombinant human N-terminal GST-tagged KDM4B (1 to 500 residues) expressed in baculovirus infected sf9 cells using biotin-H3K9me3 as substrate preincubated for 10 mins measured after 20 mins by alphascreen assay	ic50	0.0720	uM
8-[4-[2-[4-[(4-fluorophenyl)methyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282543: Inhibition of recombinant human N-terminal GST-tagged KDM4B (1 to 500 residues) expressed in baculovirus infected sf9 cells using biotin-H3K9me3 as substrate preincubated for 10 mins measured after 20 mins by alphascreen assay	ic50	0.0790	uM
8-[4-[2-[4-[4-(2-oxopyrrolidin-1-yl)phenyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556102: Inhibition of N-terminal GST-tagged recombinant human KDM4B (1 to 500 residues) expressed in baculovirus infected Sf9 insect cells 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	0.0790	uM
2-(2-amino-1,3-thiazol-4-yl)pyridine-4-carboxylic acid	1282543: Inhibition of recombinant human N-terminal GST-tagged KDM4B (1 to 500 residues) expressed in baculovirus infected sf9 cells using biotin-H3K9me3 as substrate preincubated for 10 mins measured after 20 mins by alphascreen assay	ic50	0.0830	uM
8-[4-[2-[4-(4-chlorophenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282543: Inhibition of recombinant human N-terminal GST-tagged KDM4B (1 to 500 residues) expressed in baculovirus infected sf9 cells using biotin-H3K9me3 as substrate preincubated for 10 mins measured after 20 mins by alphascreen assay	ic50	0.0860	uM
2-[[[2-[2-(dimethylamino)ethyl-ethylamino]-2-oxoethyl]amino]methyl]pyridine-4-carboxylic acid	1289436: Inhibition of human N-terminal GST-tagged KDM4B (1 to 500 residues) expressed in baculovirus infected sf9 cells using biotinylated histone H3 as substrate preincubated for 10 mins followed by substrate addition measured after 10 mins by AlphaLisa assay	ic50	0.1000	uM
8-[4-[2-[4-(3-propan-2-ylphenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556102: Inhibition of N-terminal GST-tagged recombinant human KDM4B (1 to 500 residues) expressed in baculovirus infected Sf9 insect cells 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	0.1010	uM
8-[4-[2-[4-[3-(2-morpholin-4-ylethyl)-5-(trifluoromethyl)phenyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556102: Inhibition of N-terminal GST-tagged recombinant human KDM4B (1 to 500 residues) expressed in baculovirus infected Sf9 insect cells 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	0.1020	uM
8-[4-[2-(4-benzylpiperidin-1-yl)ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282543: Inhibition of recombinant human N-terminal GST-tagged KDM4B (1 to 500 residues) expressed in baculovirus infected sf9 cells using biotin-H3K9me3 as substrate preincubated for 10 mins measured after 20 mins by alphascreen assay	ic50	0.1180	uM
8-[4-[2-[4-[3-(2-methylpropoxy)phenyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556102: Inhibition of N-terminal GST-tagged recombinant human KDM4B (1 to 500 residues) expressed in baculovirus infected Sf9 insect cells 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	0.1450	uM
8-[4-[2-[4-[(3-methoxyphenyl)methyl]piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1282543: Inhibition of recombinant human N-terminal GST-tagged KDM4B (1 to 500 residues) expressed in baculovirus infected sf9 cells using biotin-H3K9me3 as substrate preincubated for 10 mins measured after 20 mins by alphascreen assay	ic50	0.1490	uM
8-[4-[2-[4-(4-pyridin-2-ylphenyl)piperidin-1-yl]ethyl]pyrazol-1-yl]-3H-pyrido[3,4-d]pyrimidin-4-one	1556102: Inhibition of N-terminal GST-tagged recombinant human KDM4B (1 to 500 residues) expressed in baculovirus infected Sf9 insect cells 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	0.1530	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Valproic Acid	affects cotreatment, decreases expression, affects expression, increases methylation	5
Benzo(a)pyrene	decreases expression, increases methylation	4
Cisplatin	decreases expression, affects cotreatment, increases expression	3
trichostatin A	increases expression, affects expression	2
cobaltous chloride	increases expression, decreases reaction	2
Doxorubicin	decreases expression, affects cotreatment, affects response to substance	2
Estradiol	increases expression	2
TAK-243	increases sumoylation	1
methylmercuric chloride	decreases expression	1
triphenyl phosphate	affects expression	1
uranyl acetate	increases expression	1
bisphenol A	decreases methylation	1
zinc chloride	decreases reaction, increases expression	1
sodium arsenite	increases expression	1
nickel chloride	increases expression	1
3,4,5,3’,4’-pentachlorobiphenyl	affects binding, increases reaction, increases expression	1
benzo(e)pyrene	increases methylation	1
3,4,3’,4’-tetrachlorobiphenyl	affects binding, increases reaction, increases expression	1
2,3-bis(3’-hydroxybenzyl)butyrolactone	decreases expression	1
aflatoxin B2	decreases methylation	1
coumarin	decreases phosphorylation	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	decreases expression, affects cotreatment	1
abrine	increases expression	1
dorsomorphin	affects cotreatment, decreases expression	1
2-(1H-indazol-4-yl)-6-(4-methanesulfonylpiperazin-1-ylmethyl)-4-morpholin-4-ylthieno(3,2-d)pyrimidine	increases expression, increases response to substance	1
bisphenol S	decreases methylation	1
jinfukang	affects cotreatment, increases expression	1
(+)-JQ1 compound	increases expression	1
Bortezomib	decreases expression	1
Vorinostat	decreases expression	1

ChEMBL screening assays

61 unique, capped per target: 60 binding, 1 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL3363695	Binding	Inhibition of recombinant human KDM4B (1 to 348 aa) expressed in Escherichia coli using calf thymus histone H3 as substrate after 30 mins by Western blotting	KDM4B as a target for prostate cancer: structural analysis and selective inhibition by a novel inhibitor. — J Med Chem
CHEMBL5723217	Functional	Affinity Biochemical interaction: (AlphaScreen) EUB0002543a KDM4B	Affinity Biochemical Literature for EUbOPEN Chemogenomic Library

Cellosaurus cell lines

2 cell lines: 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_SU30	HAP1 KDM4B (-) 1	Cancer cell line	Male
CVCL_SU31	HAP1 KDM4B (-) 2	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04586348	PHASE4	UNKNOWN	Prenatal Iodine Supplementation and Early Childhood Neurodevelopment
NCT04873115	PHASE4	UNKNOWN	Double-blind, Placebo-controlled, Randomized Clinical Trial Comparing the Efficacy and Safety of Sialanar Plus orAl rehabiLitation Against Placebo Plus Oral Rehabilitation for chIldren and Adolescents With seVere Sialorrhoea and Neurodisabilties,
NCT02559102	PHASE3	COMPLETED	Dexmedetomidine Sedation Versus General Anaesthesia for Inguinal Hernia Surgery in Infants
NCT02757079	PHASE3	COMPLETED	Study of the Efficacy and Safety of NPC-15 for Sleep Disorders of Children With Neurodevelopmental Disorders
NCT06915480	PHASE3	RECRUITING	Reducing Missed Appointments
NCT07377032	PHASE3	RECRUITING	TAP-GRIN: Interventional Study on Patients With GRIN-related Neurodevelopmental Disorders
NCT02909959	PHASE2	COMPLETED	Sulforaphane for the Treatment of Young Men With Autism Spectrum Disorder
NCT06081348	PHASE2	RECRUITING	Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
NCT06352372	PHASE2	COMPLETED	Safety and Efficacy of tPBM for Epileptiform Activity in Autism
NCT00503191	PHASE1	COMPLETED	NeuroModulation Technique Treatment of Autism
NCT04475848	PHASE1	COMPLETED	A Study to Investigate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Food Effect of RO6953958 in Healthy Participants
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