KDM4C

Summary

KDM4C (lysine demethylase 4C, HGNC:17071) is a protein-coding gene on chromosome 9p24.1, encoding Lysine-specific demethylase 4C (Q9H3R0). Histone demethylase that specifically demethylates ‘Lys-9’ and ‘Lys-36’ residues of histone H3, thereby playing a central role in histone code.

This gene is a member of the Jumonji domain 2 (JMJD2) family. The encoded protein is a trimethylation-specific demethylase, and converts specific trimethylated histone residues to the dimethylated form. This enzymatic action regulates gene expression and chromosome segregation. Chromosomal aberrations and changes in expression of this gene may be found in tumor cells. Alternative splicing results in multiple transcript variants.

Source: NCBI Gene 23081 — RefSeq curated summary.

At a glance

• GWAS associations: 31
• Clinical variants (ClinVar): 219 total — 1 pathogenic
• Druggable target: yes — 4 molecules with ChEMBL bioactivity
• MANE Select transcript: NM_015061

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:17071
Approved symbol	KDM4C
Name	lysine demethylase 4C
Location	9p24.1
Locus type	gene with protein product
Status	Approved
Aliases	GASC1, KIAA0780, TDRD14C
Ensembl gene	ENSG00000107077
Ensembl biotype	protein_coding
OMIM	605469
Entrez	23081

Gene structure

Transcript identifiers

Ensembl transcripts: 24 — 16 protein_coding, 7 protein_coding_CDS_not_defined, 1 nonsense_mediated_decay

ENST00000381306, ENST00000381309, ENST00000401787, ENST00000420847, ENST00000428870, ENST00000438023, ENST00000466673, ENST00000480996, ENST00000489243, ENST00000490806, ENST00000494570, ENST00000495890, ENST00000496464, ENST00000536108, ENST00000543771, ENST00000871061, ENST00000871062, ENST00000871063, ENST00000934139, ENST00000948679, ENST00000948680, ENST00000948681, ENST00000948682, ENST00000948683

RefSeq mRNA: 11 — MANE Select: NM_015061 NM_001146695, NM_001146696, NM_001304339, NM_001304340, NM_001304341, NM_001353997, NM_001353998, NM_001353999, NM_001354000, NM_001354001, NM_015061

CCDS: CCDS55286, CCDS6471, CCDS78379

Canonical transcript exons

ENST00000381309 — 22 exons

Exon	Start	End
ENSE00001605536	7169798	7169890
ENSE00001917727	7174553	7175648
ENSE00003485374	6792972	6793132
ENSE00003600350	7165238	7165357
ENSE00003657141	7103685	7103870
ENSE00003664022	7128066	7128236
ENSE00003802098	7015853	7015929
ENSE00003802148	7046862	7046917
ENSE00003802500	6986344	6986666
ENSE00003802576	6880012	6880061
ENSE00003802906	6984166	6984404
ENSE00003803374	6887960	6888063
ENSE00003804480	6805599	6805774
ENSE00003804507	6849507	6849700
ENSE00003804746	7049092	7049200
ENSE00003805648	6893095	6893232
ENSE00003806474	6814631	6814745
ENSE00003807447	6980925	6981118
ENSE00003808035	7013788	7014001
ENSE00003808552	7011698	7011879
ENSE00003810588	6990416	6990524
ENSE00003903751	6757973	6758203

Expression profiles

Bgee: expression breadth ubiquitous, 250 present calls, max score 93.91.

FANTOM5 (CAGE): breadth ubiquitous, TPM avg 24.1644 / max 259.7205, expressed in 1810 samples.

FANTOM5 promoters (14 alternative TSS)

Promoter ID	TPM avg	Samples expressed
96012	7.9026	1638
96011	3.4697	1290
96005	3.4553	1324
96010	2.7795	1036
96007	1.4109	766
96013	1.2293	727
96014	1.1429	594
96008	0.9350	593
96009	0.4980	259
96003	0.4734	167

Top tissues by expression

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

Tissue	Anatomy ID	Expression score	Quality
right hemisphere of cerebellum	UBERON:0014890	93.91	gold quality
cerebellar hemisphere	UBERON:0002245	93.84	gold quality
cerebellar cortex	UBERON:0002129	93.82	gold quality
cerebellum	UBERON:0002037	92.80	gold quality
colonic epithelium	UBERON:0000397	92.50	gold quality
bone marrow cell	CL:0002092	90.85	gold quality
tonsil	UBERON:0002372	89.71	gold quality
calcaneal tendon	UBERON:0003701	89.45	gold quality
sural nerve	UBERON:0015488	89.14	gold quality
corpus callosum	UBERON:0002336	89.10	gold quality
body of pancreas	UBERON:0001150	89.01	gold quality
monocyte	CL:0000576	88.51	gold quality
mononuclear cell	CL:0000842	88.47	gold quality
leukocyte	CL:0000738	88.39	gold quality
granulocyte	CL:0000094	88.01	gold quality
rectum	UBERON:0001052	87.76	gold quality
cerebellar vermis	UBERON:0004720	87.71	gold quality
pancreas	UBERON:0001264	87.35	gold quality
stomach	UBERON:0000945	87.20	gold quality
body of stomach	UBERON:0001161	87.17	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	87.09	gold quality
skin of leg	UBERON:0001511	86.89	gold quality
skin of abdomen	UBERON:0001416	86.73	gold quality
small intestine Peyer’s patch	UBERON:0003454	86.51	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	86.40	gold quality
lymph node	UBERON:0000029	86.39	gold quality
bone marrow	UBERON:0002371	86.27	gold quality
transverse colon	UBERON:0001157	86.16	gold quality
adrenal tissue	UBERON:0018303	86.10	gold quality
adenohypophysis	UBERON:0002196	85.90	gold quality

Single-cell (SCXA)

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

Experiment	Marker?	Max mean expression
E-ANND-3	yes	6.12

Regulation

Is transcription factor: yes

Downstream targets (CollecTRI)

2 targets.

Target	Regulation
H2AX	Repression
JAG1	Activation

Upstream regulators (CollecTRI, top): AR, E2F1, EPAS1, HIF1A, POU5F1

miRNA regulators (miRDB)

89 targeting KDM4C, 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-1277-5P	100.00	73.95	5056
HSA-MIR-5011-5P	100.00	83.46	5820
HSA-MIR-3163	100.00	77.23	8605
HSA-MIR-6748-5P	100.00	65.81	1057
HSA-MIR-3924	100.00	72.09	2394
HSA-MIR-340-5P	100.00	72.50	4437
HSA-MIR-9-5P	100.00	72.28	2361
HSA-MIR-4789-3P	99.99	70.75	2484
HSA-MIR-548C-3P	99.99	74.01	7587
HSA-MIR-4282	99.99	75.36	6408
HSA-MIR-520D-5P	99.98	73.34	4883
HSA-MIR-524-5P	99.98	73.43	4882
HSA-MIR-548N	99.98	71.94	4170
HSA-MIR-3148	99.97	75.06	6478
HSA-MIR-3688-3P	99.97	72.02	2834
HSA-MIR-548AJ-3P	99.96	73.38	5345
HSA-MIR-548X-3P	99.96	73.38	5345
HSA-MIR-6772-5P	99.94	67.01	577
HSA-MIR-548J-3P	99.94	72.61	4881
HSA-MIR-548AE-3P	99.93	72.66	4867
HSA-MIR-548AH-3P	99.93	72.54	4872
HSA-MIR-548AM-3P	99.93	72.54	4872
HSA-MIR-548AQ-3P	99.93	72.66	4867
HSA-MIR-7-1-3P	99.91	71.53	4384
HSA-MIR-7-2-3P	99.91	71.40	4394
HSA-MIR-3686	99.90	70.53	2432
HSA-MIR-345-3P	99.89	70.23	1421
HSA-MIR-6124	99.87	69.78	3551
HSA-MIR-30A-3P	99.87	69.74	2928
HSA-MIR-30D-3P	99.87	69.92	2917

Literature-anchored findings (GeneRIF, showing 40)

• GASC1 interacts with H3K9me3; three members of this subfamily of proteins demethylate H3K9me3/me2 in vitro through a hydroxylation reaction requiring iron and alpha-ketoglutarate as cofactors (PMID:16732293)
• JMJD2C and LSD1 interact and both demethylases cooperatively stimulate androgen receptor-dependent gene transcription. (PMID:17277772)
• JMJD2C is the histone demethylase implicated in the epigenetic reprogramming during the early embryogenesis. (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)
• Gene rearrangements of JMJD2C is associated with mucosa-associated lymphoid tissue lymphoma. (PMID:18927281)
• GASC1 is a driving oncogene in the 9p23-24 amplicon in human breast cancer. (PMID:19784073)
• identification of genetic alterations & expression changes of LSD1, JHDM2A & GASC1 in prostate cancer (PC); as no genetic alterations & only modest expression changes were found, it is unlikely they play a major role in progression of PC (PMID:20127736)
• The strongest association in obsessive-compulsive disorder has been found at rs301443 (P=0.000067) residing between SLC1A1 and JMJD2C at 9p24. (PMID:20410850)
• inhibition measurements showed significant selectivity between KDM4C and KDM6A (PMID:21575637)
• This study presented that KDM4C showed strong associations with alcohol withdrawal symptoms (p < 5 x 10-5). (PMID:22072270)
• JMJD2C displays an optimal activity in vitro at alphaKG concentrations similar to those found in cancer cells, with implications for the regulation of histone demethylation activity in cancer versus normal cells. (PMID:23067339)
• JMJD2C decreases trimethylation of histone H3 at lysine 9, and enhances HIF-1 binding to hypoxia response elements, thereby activating transcription of proteins that are required for metabolic reprogramming and for lung metastasis. (PMID:23129632)
• Patients with GASC1 positive tumors have better breast cancer specific survival and respond better to radiotherapy and hormonal treatment (PMID:23148692)
• analysis of the nickel-induced inhibition of truncated constructs of JMJD2A and JMJD2C histone demethylases using X-ray absorption spectroscopy (PMID:23692052)
• KDM4C maintains the sphere-forming capacity in CRCs by mediating the beta-catenin-dependent transcription of JAG1 in a feed-forward manner. (PMID:23698634)
• KDM4C promotes transcriptional activation by removing the repressive histone mark, H3K9me3, from its target genes. Variation in its expression leads to differences in the growth of normal and some cancer cells. (PMID:24285722)
• GASC1 expression is higher in adenocarcinoma than squamous cell carcinoma. Smoking decreases GASC1 expression in tumor cells, indicating that tobacco smoke may influence the methylation of histone 3 lysine residues in lung cancer. (PMID:24371038)
• Data suggest that D396N polymorphism of JmjC domain-containing histone demethylase JMJD2C affects the prognosis of breast cancer by altering caspase-3 cleavage and the ability of double strand DNA break repair which may contribute to therapy resistance. (PMID:24952432)
• JMJD2B and JMJD2C play an important role in the pathology of osteosarcoma via the up-regulation of FGF2. (PMID:25636512)
• KDM4C recognition of H3K4me3 stimulates demethylation of H3K9me3 in cis on peptide and mononucleosome substrates. (PMID:26747609)
• Pharmacological inhibition of KDM4C/PRMT1 suppresses transcription and transformation ability of MLL fusions (PMID:26766589)
• JMJD2C regulated the activities of lung cancer cells by directly controlling the expression of CUL4A in JMJD2C over-expression cell line. (PMID:28236704)
• histone H3 lysine 9 methylation reduction, which may be due to the downregulation of methyltransferase SUV39H2 and the upregulation of demethylase KDM4C, was found in CD4(+) T lymphocytes of Latent autoimmune diabetes in adult patients (PMID:28396876)
• we have identified KDM4C as a new risk gene shared between systemic vasculitides, consistent with the increasing evidences of the crucial role that the epigenetic mechanisms have in the development of complex immune-mediated conditions. (PMID:29374629)
• LSD1 and JMJD2C disable oncogenic Ras- or Braf-induced senescence by enabling the expression of E2F target genes (PMID:29438700)
• data indicate that circKDM4C might have considerable potential as a prognostic biomarker in breast cancer, and support the notion that therapeutic targeting of circKDM4C/miR-548p/PBLD axis may be a promising treatment approach for breast cancer patients (PMID:31406252)
• Data found that JMJD2C was overexpressed in colorectal cancer (CRC) tumor and metastatic foci, and CRC patients with lower JMJD2C expression had better prognosis. JMJD2C could enhance the metastatic abilities of CRC cells in vitro and in vivo by regulating the histone methylation level of MALAT1 promoter, thereby up-regulating the expression of MALAT1 and enhancing the activity of beta-catenin signaling pathway. (PMID:31665047)
• Wnt-Induced Stabilization of KDM4C Is Required for Wnt/beta-Catenin Target Gene Expression and Glioblastoma Tumorigenesis. (PMID:31888886)
• Harnessing stemness and PD-L1 expression by AT-rich interaction domain-containing protein 3B in colorectal cancer. (PMID:32483441)
• microRNA-216b enhances cisplatin-induced apoptosis in osteosarcoma MG63 and SaOS-2 cells by binding to JMJD2C and regulating the HIF1alpha/HES1 signaling axis. (PMID:32972441)
• Rare genetic variants in the gene encoding histone lysine demethylase 4C (KDM4C) and their contributions to susceptibility to schizophrenia and autism spectrum disorder. (PMID:33279929)
• Histone demethylase KDM4C controls tumorigenesis of glioblastoma by epigenetically regulating p53 and c-Myc. (PMID:33462212)
• JMJD2C triggers the growth of multiple myeloma cells via activation of betacatenin. (PMID:33469678)
• USP9X-mediated KDM4C deubiquitination promotes lung cancer radioresistance by epigenetically inducing TGF-beta2 transcription. (PMID:33558705)
• GASC1 promotes glioma progression by enhancing NOTCH1 signaling. (PMID:33649841)
• GASC1 promotes hepatocellular carcinoma progression by inhibiting the degradation of ROCK2. (PMID:33692332)
• UHRF1 promotes androgen receptor-regulated CDC6 transcription and anti-androgen receptor drug resistance in prostate cancer through KDM4C-Mediated chromatin modifications. (PMID:34265399)
• Novel germline variant in the histone demethylase and transcription regulator KDM4C induces a multi-cancer phenotype. (PMID:34281993)
• Disruption of KDM4C-ALDH1A3 feed-forward loop inhibits stemness, tumorigenesis and chemoresistance of gastric cancer stem cells. (PMID:34548470)
• JMJD2C-mediated long non-coding RNA MALAT1/microRNA-503-5p/SEPT2 axis worsens non-small cell lung cancer. (PMID:35046387)

Cross-species orthologs

7 orthologs

Organism	Symbol	Gene ID
danio_rerio	kdm4aa	ENSDARG00000018782
danio_rerio	kdm4ab	ENSDARG00000019103
mus_musculus	Kdm4c	ENSMUSG00000028397
rattus_norvegicus	Kdm4c	ENSRNOG00000006644
drosophila_melanogaster	Kdm4A	FBGN0033233
drosophila_melanogaster	Kdm4B	FBGN0053182
caenorhabditis_elegans		WBGENE00012982

Paralogs (10): JARID2 (ENSG00000008083), KDM5D (ENSG00000012817), KDM4A (ENSG00000066135), KDM5A (ENSG00000073614), KDM5B (ENSG00000117139), KDM5C (ENSG00000126012), KDM4B (ENSG00000127663), KDM4D (ENSG00000186280), KDM4E (ENSG00000235268), KDM4F (ENSG00000255855)

Protein

Protein identifiers

Lysine-specific demethylase 4C — Q9H3R0 (reviewed: Q9H3R0)

Alternative names: Gene amplified in squamous cell carcinoma 1 protein, JmjC domain-containing histone demethylation protein 3C, Jumonji domain-containing protein 2C, [histone H3]-trimethyl-L-lysine(9) demethylase 4C

All UniProt accessions (5): Q9H3R0, A0A0A0MSR6, B0QZ60, C9J879, F8WCN1

UniProt curated annotations — full annotation on UniProt →

Function. Histone demethylase that specifically demethylates ‘Lys-9’ and ‘Lys-36’ residues of histone H3, thereby playing a central role in histone code. Does not demethylate histone H3 ‘Lys-4’, H3 ‘Lys-27’ nor H4 ‘Lys-20’. Demethylates trimethylated H3 ‘Lys-9’ and H3 ‘Lys-36’ residue, while it has no activity on mono- and dimethylated residues. Demethylation of Lys residue generates formaldehyde and succinate.

Subcellular location. Nucleus.

Tissue specificity. Overexpressed in several esophageal squamous cell carcinomas (ESCs).

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 (4)

UniProt ID	Names	Canonical?
Q9H3R0-1	1	yes
Q9H3R0-2	2
Q9H3R0-3	3
Q9H3R0-4	4

RefSeq proteins (11): NP_001140167, NP_001140168, NP_001291268, NP_001291269, NP_001291270, NP_001340926, NP_001340927, NP_001340928, NP_001340929, NP_001340930, NP_055876* (*=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

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 (86 total): strand 24, helix 20, binding site 11, sequence variant 7, domain 4, splice variant 4, region of interest 3, sequence conflict 3, turn 3, zinc finger region 3, compositionally biased region 2, chain 1, mutagenesis site 1

Structure

Experimental structures (PDB)

7 structures.

PDB	Method	Resolution (Å)
2XDP	X-RAY DIFFRACTION	1.56
5FJK	X-RAY DIFFRACTION	1.66
5KR7	X-RAY DIFFRACTION	1.9
4XDO	X-RAY DIFFRACTION	1.97
4XDP	X-RAY DIFFRACTION	2.07
5FJH	X-RAY DIFFRACTION	2.1
2XML	X-RAY DIFFRACTION	2.55

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q9H3R0-F1	72.32	0.43

Functional residue map

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

Ligand- & substrate-binding residues (11): 134; 190; 192; 200; 208; 236; 242; 243; 278; 308; 310

Mutagenesis-validated functional residues (1):

Position	Phenotype
190–192	abolishes lysine-specific histone demethylase activity.

Function

Pathways and Gene Ontology

Reactome pathways

9 pathways

ID	Pathway
R-HSA-3214842	HDMs demethylate histones
R-HSA-5625886	Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3
R-HSA-162582	Signal Transduction
R-HSA-194315	Signaling by Rho GTPases
R-HSA-195258	RHO GTPase Effectors
R-HSA-3247509	Chromatin modifying enzymes
R-HSA-4839726	Chromatin organization
R-HSA-5625740	RHO GTPases activate PKNs
R-HSA-9716542	Signaling by Rho GTPases, Miro GTPases and RHOBTB3

MSigDB gene sets: 197 (showing top): GOBP_EMBRYO_DEVELOPMENT_ENDING_IN_BIRTH_OR_EGG_HATCHING, GOMF_OXIDOREDUCTASE_ACTIVITY_ACTING_ON_PAIRED_DONORS_WITH_INCORPORATION_OR_REDUCTION_OF_MOLECULAR_OXYGEN, GOBP_CELLULAR_RESPONSE_TO_LIPID, MENSE_HYPOXIA_UP, GOBP_REGULATION_OF_INTRACELLULAR_STEROID_HORMONE_RECEPTOR_SIGNALING_PATHWAY, TAL1ALPHAE47_01, GOBP_BLASTOCYST_FORMATION, CAGCTG_AP4_Q5, GOBP_REGULATION_OF_ANDROGEN_RECEPTOR_SIGNALING_PATHWAY, GOBP_HORMONE_MEDIATED_SIGNALING_PATHWAY, GOBP_IN_UTERO_EMBRYONIC_DEVELOPMENT, MYOD_01, GOBP_CELLULAR_RESPONSE_TO_HORMONE_STIMULUS, KOYAMA_SEMA3B_TARGETS_UP, SNIJDERS_AMPLIFIED_IN_HEAD_AND_NECK_TUMORS

GO Biological Process (10): blastocyst formation (GO:0001825), chromatin remodeling (GO:0006338), positive regulation of cell population proliferation (GO:0008284), regulation of gene expression (GO:0010468), stem cell population maintenance (GO:0019827), androgen receptor signaling pathway (GO:0030521), positive regulation of transcription by RNA polymerase II (GO:0045944), regulation of androgen receptor signaling pathway (GO:0060765), regulation of stem cell differentiation (GO:2000736), chromatin organization (GO:0006325)

GO Molecular Function (11): transcription coactivator activity (GO:0003713), zinc ion binding (GO:0008270), enzyme binding (GO:0019899), histone demethylase activity (GO:0032452), histone H3K9 demethylase activity (GO:0032454), nuclear androgen receptor binding (GO:0050681), 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 (4): chromatin (GO:0000785), nucleus (GO:0005634), nucleoplasm (GO:0005654), pericentric heterochromatin (GO:0005721)

Reactome top-level categories

Rollup of top-7 pathways:

Category	Pathways
Chromatin modifying enzymes	1
RHO GTPases activate PKNs	1
Signaling by Rho GTPases, Miro GTPases and RHOBTB3	1
Signaling by Rho GTPases	1
Chromatin organization	1
RHO GTPase Effectors	1
Signal Transduction	1

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
positive regulation of DNA-templated transcription	2
histone H3 demethylase activity	2
2-oxoglutarate-dependent dioxygenase activity	2
cellular anatomical structure	2
blastocyst development	1
anatomical structure formation involved in morphogenesis	1
chromatin organization	1
cell population proliferation	1
regulation of cell population proliferation	1
positive regulation of cellular process	1
gene expression	1
regulation of macromolecule biosynthetic process	1
multicellular organismal process	1
maintenance of cell number	1
nuclear receptor-mediated steroid hormone signaling pathway	1
regulation of transcription by RNA polymerase II	1
transcription by RNA polymerase II	1
androgen receptor signaling pathway	1
regulation of intracellular steroid hormone receptor signaling pathway	1
regulation of cell differentiation	1
stem cell differentiation	1
cellular component organization	1
transcription coregulator activity	1
transition metal ion binding	1
protein binding	1
protein demethylase activity	1
histone modifying activity	1
nuclear receptor binding	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

Protein interactions and networks

STRING

1278 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
KDM4C	HIF1A	Q16665	938
KDM4C	JMJD1C	Q15652	893
KDM4C	KDM3A	Q9Y4C1	862
KDM4C	KDM1A	O60341	836
KDM4C	SUV39H1	O43463	774
KDM4C	KDM6A	O15550	744
KDM4C	EHMT2	Q96KQ7	718
KDM4C	H3-3A	P06351	703
KDM4C	H3C1	P02295	701
KDM4C	Q08EI0	Q08EI0	693
KDM4C	PRMT1	Q99873	668
KDM4C	KDM6B	O15054	666
KDM4C	KDM2B	Q8NHM5	645
KDM4C	KDM2A	Q9Y2K7	645
KDM4C	KDM3B	Q7LBC6	634

IntAct

19 interactions, top by confidence:

A	B	Type	Score
KDM4C		psi-mi:“MI:0871”(demethylation reaction)	0.440
KDM4C	CBX4	psi-mi:“MI:0871”(demethylation reaction)	0.440
KDM4C	SMCHD1	psi-mi:“MI:0914”(association)	0.350
	KDM4C	psi-mi:“MI:0914”(association)	0.350
KDM4C		psi-mi:“MI:0914”(association)	0.350
DSCAM	KDM4C	psi-mi:“MI:0915”(physical association)	0.000

BioGRID (83): KDM4C (Affinity Capture-RNA), KDM4C (Affinity Capture-RNA), KDM4C (Affinity Capture-RNA), KDM4C (Affinity Capture-RNA), KDM4C (Reconstituted Complex), HIF1A (Reconstituted Complex), KDM4C (Affinity Capture-Western), HIF1A (Affinity Capture-Western), KDM4C (Negative Genetic), KDM4C (Negative Genetic), PRMT5 (Negative Genetic), KDM4C (Synthetic Growth Defect), KDM4C (Affinity Capture-RNA), KDM4C (Affinity Capture-MS), KDM4C (Affinity Capture-MS)

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

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

SIGNOR signaling

21 interactions.

A	Effect	B	Mechanism
KDM4C	“up-regulates quantity by expression”	JAG1	“transcriptional regulation”
KDM4C	“down-regulates activity”	H2AC4	demethylation
KDM4C	“down-regulates activity”	H3C1	demethylation
KDM4C	“down-regulates activity”	H3-4	demethylation
KDM4C	“down-regulates activity”	H3-3A	demethylation
CASP3	“down-regulates activity”	KDM4C	cleavage
“Caspase 3 complex”	“down-regulates activity”	KDM4C	cleavage
KDM4C	“down-regulates quantity by repression”	H2AX	“transcriptional regulation”
KDM4C	“up-regulates activity”	HIF1A	binding
KDM4C	“up-regulates activity”	AR	binding
KDM4C	“up-regulates activity”	KDM1A	binding
KDM4C	“down-regulates activity”	“Histone H2A”	demethylation
KDM4C	“down-regulates activity”	“Histone H3”	demethylation
HIF1A	“up-regulates quantity by expression”	KDM4C	“transcriptional regulation”
EPAS1	“up-regulates quantity by expression”	KDM4C	“transcriptional regulation”
EIF2AK2	“down-regulates quantity by destabilization”	KDM4C	phosphorylation
2-oxoglutarate(2-)	“up-regulates activity”	KDM4C	“chemical activation”

Disease & clinical

Clinical variants and AI predictions

ClinVar

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

Classification	Count (floor)
Pathogenic	1
Likely pathogenic	0
Uncertain significance	164
Likely benign	15
Benign	7

Top pathogenic / likely-pathogenic (1)

Variant ID	HGVS	Classification
563673	GRCh37/hg19 9p24.3-24.1(chr9:203861-7007586)x1	Pathogenic

SpliceAI

8062 predictions. Top by Δscore:

Variant	Effect	Δscore
9:6720995:CAGGT:C	donor_loss	1.0000
9:6720996:AGGTG:A	donor_loss	1.0000
9:6720997:GGTG:G	donor_loss	1.0000
9:6720998:G:C	donor_loss	1.0000
9:6792967:TCCA:T	acceptor_loss	1.0000
9:6792968:CCA:C	acceptor_loss	1.0000
9:6792969:CA:C	acceptor_loss	1.0000
9:6792969:CAGAC:C	acceptor_loss	1.0000
9:6792970:A:AG	acceptor_gain	1.0000
9:6792970:A:AT	acceptor_loss	1.0000
9:6792970:AGAC:A	acceptor_loss	1.0000
9:6792971:G:A	acceptor_loss	1.0000
9:6792971:G:GT	acceptor_gain	1.0000
9:6792971:GA:G	acceptor_gain	1.0000
9:6792971:GAC:G	acceptor_gain	1.0000
9:6792971:GACA:G	acceptor_gain	1.0000
9:6792971:GACAC:G	acceptor_gain	1.0000
9:6793128:CAAAG:C	donor_loss	1.0000
9:6793129:AAAG:A	donor_loss	1.0000
9:6793130:AAGGT:A	donor_loss	1.0000
9:6793131:AGGTG:A	donor_loss	1.0000
9:6793132:GGT:G	donor_loss	1.0000
9:6793133:G:GA	donor_loss	1.0000
9:6793133:GT:G	donor_loss	1.0000
9:6793134:T:G	donor_loss	1.0000
9:6805591:A:AG	acceptor_gain	1.0000
9:6805594:TTTA:T	acceptor_loss	1.0000
9:6805595:TTA:T	acceptor_loss	1.0000
9:6805595:TTAG:T	acceptor_loss	1.0000
9:6805596:TA:T	acceptor_loss	1.0000

AlphaMissense

7014 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
9:6805617:T:A	W55R	1.000
9:6805617:T:C	W55R	1.000
9:6805704:T:C	F84L	1.000
9:6805706:C:A	F84L	1.000
9:6805706:C:G	F84L	1.000
9:6805749:T:C	F99L	1.000
9:6805750:T:C	F99S	1.000
9:6805751:C:A	F99L	1.000
9:6805751:C:G	F99L	1.000
9:6814680:T:A	W124R	1.000
9:6814680:T:C	W124R	1.000
9:6814713:G:C	G135R	1.000
9:6814714:G:A	G135D	1.000
9:6849519:T:A	W150R	1.000
9:6849519:T:C	W150R	1.000
9:6849604:T:C	L178P	1.000
9:6849609:T:C	F180L	1.000
9:6849611:T:A	F180L	1.000
9:6849611:T:G	F180L	1.000
9:6849612:G:C	G181R	1.000
9:6849613:G:A	G181D	1.000
9:6849618:T:A	W183R	1.000
9:6849618:T:C	W183R	1.000
9:6849619:G:C	W183S	1.000
9:6849620:G:C	W183C	1.000
9:6849620:G:T	W183C	1.000
9:6849623:G:C	K184N	1.000
9:6849623:G:T	K184N	1.000
9:6849636:T:A	W189R	1.000
9:6849636:T:C	W189R	1.000

dbSNP variants (sampled 300 via entrez): RS1000007355 (9:7020223 C>G), RS1000008183 (9:6991699 C>T), RS1000013748 (9:7144643 C>G), RS1000021492 (9:6830005 C>A,G,T), RS1000022519 (9:7044984 G>T), RS1000023464 (9:7138380 G>A), RS1000023956 (9:6729917 C>G), RS1000029624 (9:7083126 A>G), RS1000034643 (9:7170132 A>G,T), RS1000043241 (9:7078675 C>T), RS1000055977 (9:6932333 A>G), RS1000065427 (9:7012479 T>A,G), RS1000077663 (9:6987424 G>C), RS1000086312 (9:7084050 G>A,C), RS1000088620 (9:7102586 C>G)

Disease associations

OMIM: gene MIM:605469 | disease phenotypes: MIM:166000, MIM:614569

GenCC curated gene-disease

Mondo (2): Ollier disease (MONDO:0008145), Maffucci syndrome (MONDO:0013808)

Orphanet (2): Ollier disease (Orphanet:296), Maffucci syndrome (Orphanet:163634)

HPO phenotypes

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

GWAS associations

31 associations (top):

Study	Trait	p-value
GCST000823_6	Radiation response	5.000000e-06
GCST001738_12	Response to fenofibrate (adiponectin levels)	5.000000e-06
GCST001762_128	Obesity-related traits	2.000000e-06
GCST001762_353	Obesity-related traits	1.000000e-06
GCST001762_771	Obesity-related traits	6.000000e-06
GCST002541_69	Menarche (age at onset)	5.000000e-09
GCST002541_70	Menarche (age at onset)	6.000000e-11
GCST002783_409	Body mass index	3.000000e-07
GCST002783_534	Body mass index	8.000000e-07
GCST002818_6	HIV-1 susceptibility	2.000000e-06
GCST002875_147	Diisocyanate-induced asthma	7.000000e-07
GCST003252_7	Systemic lupus erythematosus	8.000000e-06
GCST005998_18	Alanine transaminase levels	2.000000e-08
GCST007201_104	Schizophrenia	6.000000e-08
GCST007201_300	Schizophrenia	3.000000e-07
GCST008525_1	Artificially sweetened beverage consumption	2.000000e-06
GCST009240_172	Serum metabolite levels (CMS)	1.000000e-09
GCST009242_348	Serum metabolite levels	9.000000e-07
GCST009305_12	California verbal learning test score	2.000000e-07
GCST010988_386	Adult body size	9.000000e-09
GCST010989_145	Body size at age 10	2.000000e-15
GCST011124_5	Caffeine consumption from tea	4.000000e-09
GCST011352_32	Alanine aminotransferase levels	1.000000e-08
GCST012020_403	Serum metabolite levels	2.000000e-34
GCST012020_404	Serum metabolite levels	3.000000e-50
GCST012020_575	Serum metabolite levels	1.000000e-10
GCST012021_23	Serum metabolite levels	1.000000e-10
GCST012636_1	Systemic vasculitis	6.000000e-07
GCST90002396_401	Mean reticulocyte volume	4.000000e-12
GCST90002397_674	Mean spheric corpuscular volume	3.000000e-14

EFO canonical traits (11, from GWAS)

EFO ID	Trait name
EFO:0004530	triglyceride measurement
EFO:0005109	energy expenditure
EFO:0004703	age at menarche
EFO:0004340	body mass index
EFO:0000180	HIV-1 infection
EFO:0006995	response to diisocyanate
EFO:0010096	artificially sweetened beverage consumption measurement
EFO:0004874	memory performance
EFO:0009819	comparative body size at age 10, self-reported
EFO:0010091	tea consumption measurement
EFO:0010701	mean reticulocyte volume

Drugs & pharmacology

Drug and pharmacology data

Is drug target: yes

ChEMBL targets (2): CHEMBL6175 (SINGLE PROTEIN), CHEMBL6195528 (PROTEIN-PROTEIN INTERACTION)

Molecules with ChEMBL bioactivity

4 molecules (phase ≥1), by development phase (incl. off-target/promiscuous compounds). Patent mentions across the top 20 by phase: 35,106 (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
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

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

Ligand	Action	Affinity	Parameter
zavondemstat	Inhibition	7.0	pIC50
IOX1	Inhibition	6.22	pIC50

Binding affinities (BindingDB)

680 measured of 1078 human assays (1078 total across all organisms); most potent 50 below. Values come from heterogeneous assays and are not directly comparable.

Ligand	Measure	Value	Patent
2-{1-[2-(2-ethoxyphenyl)ethyl]-1H-imidazol-4-yl}-4- [5-(trifluoromethyl)-1H-1,2,3-triazol-4-yl]pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
4-[5-(trifluoromethyl)-1H-1,2,3-triazol-4-yl]-2- (1-{2-[2-(trifluoromethyl)phenyl]ethyl}-1H- imidazol-4-yl)pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
2-[1-(2-methyl-1-phenylpropyl)-1H-imidazol-4-yl]-4- [5-(trifluoromethyl)-1H-1,2,3-triazol-4-yl]pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
2-{1-[2-(2-chloro-6-fluorophenyl)ethyl]-1H- imidazol-4-yl}-4-[5-(trifluoromethyl)-1H-1,2,3- triazol-4-yl]pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
2-{1-[(2,3-dihydro-1H-inden-1-yl)methyl]-1H- imidazol-4-yl}-4-[5-(trifluoromethyl)-1H-1,2,3- triazol-4-yl]pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
4-[5-(trifluoromethyl)-1H-1,2,3-triazol-4-yl]-2-(1-{2- [4-(trifluoromethyl)phenyl]ethyl}-1H-imidazol-4- yl)pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
2-{1-[2-(4-ethylphenyl)ethyl]-1H-imidazol-4-yl}-4- [5-(trifluoromethyl)-1H-1,2,3-triazol-4-yl]pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
2-{1-[2-(4-tert-butylphenyl)ethyl]-1H-imidazol-4- yl}-4-[5-(trifluoromethyl)-1H-1,2,3-triazol-4- yl]pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
2-{1-[(5-fluoro-1,2,3,4-tetrahydronaphthalen-1- yl)methyl]-1H-imidazol-4-yl}-4-[5-(trifluoromethyl)- 1H-1,2,3,-triazol-4-yl]pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
2-{1-[(6-fluoro-1,2,3,4-tetrahydronaphthalen-1- yl)methyl]-1H-imidazol-4-yl}-4-[5-(trifluoromethyl)- 1H-1,2,3-triazol-4-yl]pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
2-{1-[(7-fluoro-1,2,3,4-tetrahydronaphthalen-1- yl)methyl]-1H-imidazol-4-yl}-4-[5-(trifluoromethyl)- 1H-1,2,3-triazol-4-yl]pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
2-{1-[(7-methyl-1,2,3,4-tetrahydronaphthalen-1- yl)methyl]-1H-imidazol-4-yl}-4-[5-(trifluoromethyl)- 1H-1,2,3-triazol-4-yl]pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
2-{1-[(5-methoxy-1,2,3,4-tetrahydronaphthalen-1- yl)methyl]-1H-imidazol-4-yl}-4-[5-(trifluoromethyl)- 1H-1,2,3-triazol-4-yl]pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
2-{1-[(6-methoxy-1,2,3,4-tetrahydronaphthalen-1- yl)methyl]-1H-imidazol-4-yl}-4-[5-(trifluoromethyl)- 1H-1,2,3-triazol-4-yl]pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
2-{1-[(7-methoxy-1,2,3,4-tetrahydronaphthalen-1- yl)methyl]-1H-imidazol-4-yl}-4-[5-(trifluoromethyl)- 1H-1,2,3-triazol-4-yl]pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
2-{1-[(8-methoxy-1,2,3,4-tetrahydro-naphthalen-1-yl)methyl]-1H-imidazol-4-yl}-4-[5-(trifluoromethyl)-1H-1,2,3-triazol-4-yl]pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
2-(1-{[2-(2,2,2- trifluoroethoxy)phenyl]methyl}-1H- imidazol-4-yl)-4-[5-(trifluoromethyl)-1H- 1,2,3-triazol-4-yl]pyridine	IC50	300 nM	US-9896436: Histone demethylase inhibitors
2-[5-[(4-chloro-2-methylphenyl)methoxy]pyrazol-1-yl]pyridine-4-carboxylic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors
3-((1-methyl-1Hpyrrolo[2,3-b]pyridin-3-yl)amino)isonicotinic acid (N12)	IC50	550 nM	US-10336727: Histone demethylase inhibitors
2-(5-hydroxy-3-methyl-1H- pyrazol-1-yl)isonicotinic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors
2-(5-hydroxy-3,4- dimethyl-1H-pyrazol-1- yl)isonicotinic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors
2-(5-hydroxy-3-methyl-4- phenyl-1H-pyrazol-1- yl)isonicotinic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors
2-(5-hydroxy-3-propyl-1H- pyrazol-1-yl)isonicotinic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors
2-(5-hydroxy-1H-pyrazol-1- yl)isonicotinic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors
2-(5-p-tolyl-1H-pyrazol-1- yl)isonicotinic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors
2-(5-m-tolyl-1H-pyrazol-1- yl)isonicotinic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors
2-(5-(2,4-difluorophenyl)-1H- pyrazol-1-yl)isonicotinic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors
2-(5-(3,4-difluorophenyl)-1H- pyrazol-1-yl)isonicotinic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors
2-(5-(3-fluorophenyl)-1H-pyrazol- 1-yl)isonicotinic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors
2-(5-(3-hydroxyphenyl)-1H- pyrazol-1-yl)isonicotinic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors
2-(5-(4-hydroxyphenyl)-1H- pyrazol-1-yl)isonicotinic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors
2-(5-(3-hydroxy-4-methylphenyl)- 1H-pyrazol-1-yl)isonicotinic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors
2-(5-methyl-1H-pyrazol-1- yl)isonicotinic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors
2-(3-phenethyl-1H-pyrazol-1- yl)isonicotinic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors
2-(5-(benzyloxy)-3-methyl-1H- pyrazol-1-yl)isonicotinic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors
2-{5-[(4-methoxybenzyl)oxy]-1H- pyrazol-1-yl}pyridine-4- carboxylic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors
2-[5-(1H-indazol-6-ylmethoxy)- 1H-pyrazol-1-yl]pyridine-4- carboxylic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors
2-{5-[(1-methyl-1H-indazol-6- yl)methoxy]-1H-pyrazol-1- yl}pyridine-4-carboxylic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors
2-{5-[(3,4- difluorobenzyl)oxy]-1H- pyrazol-1-yl}pyridine-4- carboxylic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors
2-(5-{[4- (trifluoromethyl)benzyl]oxy}- 1H-pyrazol-1-yl)pyridine-4- carboxylic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors
2-[5-(pyridin-3-ylmethoxy)-1H- pyrazol-1-yl]pyridine-4-carboxylic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors
2-{5-[(4,4- difluorocyclohexyl)methoxy]-1H- pyrazol-1-yl}pyridine-4- carboxylic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors
2-{5-[(4-cyclopropylbenzyl)oxy]- 1H-pyrazol-1-yl}pyridine-4- carboxylic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors
2-[5-[1-(4- fluorophenyl)ethoxy]pyrazol-1- yl]pyridine-4-carboxylic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors
2-[5-[(4-fluorophenyl)methoxy]-4- methylpyrazol-1-yl]pyridine-4- carboxylic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors
2-[4-ethyl-5-[(4- fluorophenyl)methoxy]pyrazol-1- yl]pyridine-4-carboxylic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors
2-[5-[(2,4- difluorophenyl)methoxy]pyrazol- 1-yl]pyridine-4-carboxylic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors
2-[5-[(3,4- dichlorophenyl)methoxy]pyrazol- 1-yl]pyridine-4-carboxylic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors
2-[5-[(2,4- dichlorophenyl)methoxy]pyrazol- 1-yl]pyridine-4-carboxylic acid	IC50	550 nM	US-9908865: Histone demethylase inhibitors

ChEMBL bioactivities

2740 potent at pChembl≥5 of 2913 total, top 50 by pChembl (potency: 10 = 0.1 nM, 6 = 1 µM).

pChembl	Type	Value	Unit	Molecule
9.26	IC50	0.55	nM	CHEMBL5815580
9.26	IC50	0.55	nM	CHEMBL5910955
8.89	EC50	1.3	nM	CHEMBL4216044
8.66	Ki	2.2	nM	CHEMBL316034
8.66	IC50	2.2	nM	CHEMBL4204694
8.66	IC50	2.2	nM	CHEMBL5203487
8.30	IC50	5	nM	CHEMBL4225358
8.22	IC50	6	nM	CHEMBL4211946
8.10	IC50	8	nM	CHEMBL4207583
8.10	IC50	8	nM	CHEMBL1517074
8.05	IC50	9	nM	CHEMBL4216044
7.96	IC50	11	nM	CHEMBL4648732
7.92	IC50	12	nM	CHEMBL4209038
7.92	IC50	12	nM	CHEMBL4204375
7.85	IC50	14	nM	CHEMBL4229271
7.80	IC50	16	nM	CHEMBL4646339
7.77	IC50	17	nM	CHEMBL4207071
7.72	EC50	19	nM	CHEMBL4216399
7.72	IC50	19	nM	CHEMBL4228806
7.72	IC50	19	nM	CHEMBL1316847
7.72	IC50	19	nM	CHEMBL316034
7.66	IC50	22	nM	CHEMBL4205183
7.64	IC50	23	nM	CHEMBL4218675
7.64	IC50	23	nM	CHEMBL4206181
7.62	IC50	24	nM	CHEMBL4225013
7.57	IC50	27	nM	CHEMBL4215000
7.54	IC50	29	nM	CHEMBL1394266
7.51	Ki	31	nM	CHEMBL5203320
7.50	EC50	32	nM	CHEMBL4207071
7.48	IC50	33	nM	CHEMBL5203308
7.46	IC50	35	nM	CHEMBL4216044
7.46	IC50	35	nM	CHEMBL3786952
7.42	IC50	38	nM	CHEMBL4205285
7.42	IC50	38	nM	CHEMBL4228292
7.41	IC50	39	nM	CHEMBL6067729
7.39	IC50	41	nM	ZAVONDEMSTAT
7.38	IC50	42	nM	CHEMBL4640696
7.37	Ki	43.2	nM	CHEMBL3775262
7.34	IC50	46	nM	CHEMBL4203936
7.32	IC50	48	nM	CHEMBL4216399
7.30	IC50	50	nM	CHEMBL5786510
7.30	IC50	50	nM	CHEMBL6061922
7.30	IC50	50	nM	CHEMBL5798730
7.30	IC50	50	nM	CHEMBL5974556
7.30	IC50	50	nM	CHEMBL3787438
7.28	IC50	53	nM	CHEMBL4218774
7.27	IC50	54	nM	CHEMBL3785832
7.26	IC50	55	nM	CHEMBL4211201
7.26	IC50	55	nM	CHEMBL4286275
7.26	IC50	55	nM	CHEMBL4293252

PubChem BioAssay actives

316 with measured affinity, of 643 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-[[(1R)-6-(N-methylanilino)-1,2,3,4-tetrahydronaphthalen-1-yl]methylamino]pyridine-4-carboxylic acid	1379413: Inhibition of full-length KDM4C (unknown origin) expressed in human KYSE-150 cells assessed as increase in H3K36me3 level after 24 hrs by Western blot analysis	ec50	0.0013	uM
pyridine-2,4-dicarboxylic acid	1282325: Competitive inhibition of N-terminal His6-tagged KDM4C (1 to 352 residues) (unknown origin) expressed in Escherichia coli Rosetta 2(DE3)pLysS using ARK(Me3)STGGK peptide/alpha-ketoglutarate as substrate/cofactor by FDH coupling-based Lineweaver-Burk plot analysis	ki	0.0022	uM
(3R,6S,9S,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R)-12,33-dibenzyl-18-[(2S)-butan-2-yl]-27,30,36-tris(3-carbamimidamidopropyl)-39-[(1S)-1-hydroxyethyl]-24-(hydroxymethyl)-6,9,42-tris[(4-hydroxyphenyl)methyl]-5,8,11,14,17,20,23,26,29,32,35,38,41,44-tetradecaoxo-15-propan-2-yl-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43-tetradecazacyclopentatetracontane-3-carboxamide	1374014: Inhibition of KDM4C (unknown origin) expressed in Escherichia coli using biotinylated peptide as substrate pretreated for 15 mins followed by substrate addition by Alphascreen assay	ic50	0.0022	uM
(3R,6S,9S,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R)-12,33-dibenzyl-18-[(2S)-butan-2-yl]-27,30,36-tris(3-carbamimidamidopropyl)-39-[(1R)-1-hydroxyethyl]-24-(hydroxymethyl)-6,9,42-tris[(4-hydroxyphenyl)methyl]-5,8,11,14,17,20,23,26,29,32,35,38,41,44-tetradecaoxo-15-propan-2-yl-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43-tetradecazacyclopentatetracontane-3-carboxamide	1885315: Inhibition of KDM4C (unknown origin) measured by AlphaScreen assay	ic50	0.0022	uM
2-(5-phenylmethoxypyrazol-1-yl)pyridine-4-carboxylic acid	1391729: Inhibition of KDM4C (unknown origin) preincubated with enzyme	ic50	0.0050	uM
3-[[(1R)-6-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl]methylamino]pyridine-4-carboxylic acid	1379406: Inhibition of KDM4C (unknown origin) using biotinylated H3K9me3 peptide and alpha-ketoglutarate as substrate pretreated for 1 hr followed by substrate addition measured after 20 mins in presence of 0.2 mg/ml BSA by LANCE TR-FRET assay	ic50	0.0060	uM
3-[[(1R)-1,2,3,4-tetrahydronaphthalen-1-yl]methylamino]pyridine-4-carboxylic acid	1379406: Inhibition of KDM4C (unknown origin) using biotinylated H3K9me3 peptide and alpha-ketoglutarate as substrate pretreated for 1 hr followed by substrate addition measured after 20 mins in presence of 0.2 mg/ml BSA by LANCE TR-FRET assay	ic50	0.0080	uM
3-(4-methoxyphenyl)-1,6-dimethylpyrimido[5,4-e][1,2,4]triazine-5,7-dione	1650355: Inhibition of KDM4C (unknown origin) using methylated H3 peptide as substrate by chemiluminescence assay	ic50	0.0080	uM
4-(1,6-dimethyl-5,7-dioxopyrimido[5,4-e][1,2,4]triazin-3-yl)benzonitrile	1650355: Inhibition of KDM4C (unknown origin) using methylated H3 peptide as substrate by chemiluminescence assay	ic50	0.0110	uM
(3R,6S,9S,12S,18S,21S,24S,27S,30S,33S,36S)-27,33-bis[(2S)-butan-2-yl]-21,24,30-tris(3-carbamimidamidopropyl)-18-(hydroxymethyl)-36-[(4-hydroxyphenyl)methyl]-6,12-bis(1H-indol-3-ylmethyl)-34-methyl-9-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	1374014: Inhibition of KDM4C (unknown origin) expressed in Escherichia coli using biotinylated peptide as substrate pretreated for 15 mins followed by substrate addition by Alphascreen assay	ic50	0.0120	uM
3-(1,2,3,4-tetrahydronaphthalen-1-ylmethylamino)pyridine-4-carboxylic acid	1379406: Inhibition of KDM4C (unknown origin) using biotinylated H3K9me3 peptide and alpha-ketoglutarate as substrate pretreated for 1 hr followed by substrate addition measured after 20 mins in presence of 0.2 mg/ml BSA by LANCE TR-FRET assay	ic50	0.0120	uM
2-[5-[(4-cyanophenyl)methoxy]pyrazol-1-yl]pyridine-4-carboxylic acid	1391729: Inhibition of KDM4C (unknown origin) preincubated with enzyme	ic50	0.0140	uM
3-[2-(dimethylamino)phenyl]-1,6-dimethylpyrimido[5,4-e][1,2,4]triazine-5,7-dione	1650355: Inhibition of KDM4C (unknown origin) using methylated H3 peptide as substrate by chemiluminescence assay	ic50	0.0160	uM
3-[[(1R)-6-phenoxy-1,2,3,4-tetrahydronaphthalen-1-yl]methylamino]pyridine-4-carboxylic acid	1379406: Inhibition of KDM4C (unknown origin) using biotinylated H3K9me3 peptide and alpha-ketoglutarate as substrate pretreated for 1 hr followed by substrate addition measured after 20 mins in presence of 0.2 mg/ml BSA by LANCE TR-FRET assay	ic50	0.0170	uM
3-[[(1R)-6-phenylsulfanyl-1,2,3,4-tetrahydronaphthalen-1-yl]methylamino]pyridine-4-carboxylic acid	1379413: Inhibition of full-length KDM4C (unknown origin) expressed in human KYSE-150 cells assessed as increase in H3K36me3 level after 24 hrs by Western blot analysis	ec50	0.0190	uM
1,6-dimethyl-3-pyridin-4-ylpyrimido[5,4-e][1,2,4]triazine-5,7-dione	1650355: Inhibition of KDM4C (unknown origin) using methylated H3 peptide as substrate by chemiluminescence assay	ic50	0.0190	uM
2-[4-[2-(dimethylamino)ethyl]-5-[(4-fluorophenyl)methoxy]pyrazol-1-yl]pyridine-4-carboxylic acid	1391729: Inhibition of KDM4C (unknown origin) preincubated with enzyme	ic50	0.0190	uM
(3R,6S,9S,12S,18S,21S,24S,27S,30S,33S,36R)-9,33-bis[(2S)-butan-2-yl]-21,30-bis(3-carbamimidamidopropyl)-18-(hydroxymethyl)-36-[(4-hydroxyphenyl)methyl]-6,12-bis(1H-indol-3-ylmethyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-24,27-di(propan-2-yl)-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	1374014: Inhibition of KDM4C (unknown origin) expressed in Escherichia coli using biotinylated peptide as substrate pretreated for 15 mins followed by substrate addition by Alphascreen assay	ic50	0.0220	uM
(3R,6S,9S,12S,18S,21S,24S,27S,30S,33S,36S)-27,33-bis[(2S)-butan-2-yl]-21,24,30-tris(3-carbamimidamidopropyl)-18-(hydroxymethyl)-36-[(4-hydroxyphenyl)methyl]-6,12-bis(1H-indol-3-ylmethyl)-9-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	1374014: Inhibition of KDM4C (unknown origin) expressed in Escherichia coli using biotinylated peptide as substrate pretreated for 15 mins followed by substrate addition by Alphascreen assay	ic50	0.0230	uM
(3R,6S,9S,12S,18S,21S,24S,27S,30S,33S,36S)-27,33-bis[(2S)-butan-2-yl]-21,30-bis(3-carbamimidamidopropyl)-18,24-bis(hydroxymethyl)-36-[(4-hydroxyphenyl)methyl]-6,12-bis(1H-indol-3-ylmethyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-9-propan-2-yl-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	1374014: Inhibition of KDM4C (unknown origin) expressed in Escherichia coli using biotinylated peptide as substrate pretreated for 15 mins followed by substrate addition by Alphascreen assay	ic50	0.0230	uM
2-[5-[(4-fluorophenyl)methoxy]pyrazol-1-yl]pyridine-4-carboxylic acid	1391729: Inhibition of KDM4C (unknown origin) preincubated with enzyme	ic50	0.0240	uM
(3R,6S,9S,12S,15R,18S,21S,24S,27S,30S,33S,36S)-27,33-bis[(2S)-butan-2-yl]-21,24,30-tris(3-carbamimidamidopropyl)-18-(hydroxymethyl)-36-[(4-hydroxyphenyl)methyl]-6,12-bis(1H-indol-3-ylmethyl)-4,15,34-trimethyl-9-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	1374014: Inhibition of KDM4C (unknown origin) expressed in Escherichia coli using biotinylated peptide as substrate pretreated for 15 mins followed by substrate addition by Alphascreen assay	ic50	0.0270	uM
3-benzyl-1,6-dimethylpyrimido[5,4-e][1,2,4]triazine-5,7-dione	1650355: Inhibition of KDM4C (unknown origin) using methylated H3 peptide as substrate by chemiluminescence assay	ic50	0.0290	uM
2-(1H-pyrrol-2-yl)pyridine-4-carboxylic acid	1885279: Inhibition of N-terminal GST-tagged human KDM4C (2 to 372 residues) expressed in baculovirus-infected Sf9 cells measured by high-throughput mass spectrometry assay	ki	0.0310	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	1885315: Inhibition of KDM4C (unknown origin) measured by AlphaScreen assay	ic50	0.0330	uM
2-[5-[(4-chloro-2-methylphenyl)methoxy]pyrazol-1-yl]pyridine-4-carboxylic acid	1391729: Inhibition of KDM4C (unknown origin) preincubated with enzyme	ic50	0.0350	uM
(3R,6S,9S,12S,15R,18S,21S,24S,27S,30S,33S,36S)-27,33-bis[(2S)-butan-2-yl]-21,24,30-tris(3-carbamimidamidopropyl)-18-(hydroxymethyl)-36-[(4-hydroxyphenyl)methyl]-6,12-bis(1H-indol-3-ylmethyl)-15-methyl-9-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	1374014: Inhibition of KDM4C (unknown origin) expressed in Escherichia coli using biotinylated peptide as substrate pretreated for 15 mins followed by substrate addition by Alphascreen assay	ic50	0.0380	uM
2-[5-[(4-chloro-2-methoxyphenyl)methoxy]pyrazol-1-yl]pyridine-4-carboxylic acid	1391729: Inhibition of KDM4C (unknown origin) preincubated with enzyme	ic50	0.0380	uM
4-(1,6-dimethyl-5,7-dioxopyrimido[5,4-e][1,2,4]triazin-3-yl)benzenesulfonamide	1650355: Inhibition of KDM4C (unknown origin) using methylated H3 peptide as substrate by chemiluminescence assay	ic50	0.0420	uM
2-[2-hydroxy-5-[(4-hydroxybenzoyl)amino]phenyl]pyridine-4-carboxylic acid	1282325: Competitive inhibition of N-terminal His6-tagged KDM4C (1 to 352 residues) (unknown origin) expressed in Escherichia coli Rosetta 2(DE3)pLysS using ARK(Me3)STGGK peptide/alpha-ketoglutarate as substrate/cofactor by FDH coupling-based Lineweaver-Burk plot analysis	ki	0.0432	uM
(3R,6S,9S,12S,15S,18S,24S,27S,30S,33S,36S,39S,42R)-33-(2-amino-2-oxoethyl)-15,27-bis(3-carbamimidamidopropyl)-30-[(1R)-1-hydroxyethyl]-24-(hydroxymethyl)-9,36,42-tris[(4-hydroxyphenyl)methyl]-6,12,18-tris(1H-indol-3-ylmethyl)-5,8,11,14,17,20,23,26,29,32,35,38,41,44-tetradecaoxo-39-propan-2-yl-1-thia-4,7,10,13,16,19,22,25,28,31,34,37,40,43-tetradecazacyclopentatetracontane-3-carboxamide	1374014: Inhibition of KDM4C (unknown origin) expressed in Escherichia coli using biotinylated peptide as substrate pretreated for 15 mins followed by substrate addition by Alphascreen assay	ic50	0.0460	uM
(3R,6S,9S,12S,18S,21S,24S,27S,30S,33S,36S)-27,33-bis[(2S)-butan-2-yl]-21,24,30-tris(3-carbamimidamidopropyl)-18-(hydroxymethyl)-36-[(4-hydroxyphenyl)methyl]-6,12-bis(1H-indol-3-ylmethyl)-4-methyl-9-(2-methylpropyl)-5,8,11,14,17,20,23,26,29,32,35,38-dodecaoxo-1-thia-4,7,10,13,16,19,22,25,28,31,34,37-dodecazacyclononatriacontane-3-carboxamide	1374014: Inhibition of KDM4C (unknown origin) expressed in Escherichia coli using biotinylated peptide as substrate pretreated for 15 mins followed by substrate addition by Alphascreen assay	ic50	0.0530	uM
2-[5-[(4-chlorophenyl)methoxy]pyrazol-1-yl]pyridine-4-carboxylic acid	1391729: Inhibition of KDM4C (unknown origin) preincubated with enzyme	ic50	0.0540	uM
(3S,9R,12S,15S,18S,24S,27S,30S,33S,36S,39S)-30-(4-aminobutyl)-15,33-bis[(2S)-butan-2-yl]-27-[3-(diaminomethylideneamino)propyl]-24,36-bis(hydroxymethyl)-3-[(4-hydroxyphenyl)methyl]-12,18-bis(1H-indol-3-ylmethyl)-2,5,11,14,17,20,23,26,29,32,35,38-dodecaoxo-7-thia-1,4,10,13,16,19,22,25,28,31,34,37-dodecazabicyclo[37.3.0]dotetracontane-9-carboxamide	1374014: Inhibition of KDM4C (unknown origin) expressed in Escherichia coli using biotinylated peptide as substrate pretreated for 15 mins followed by substrate addition by Alphascreen assay	ic50	0.0550	uM
3-(thiophen-2-ylmethylamino)pyridine-4-carboxylic acid	1282647: Inhibition of KDM4C (unknown origin) using H3K9Me3 peptide as substrate assessed as demethylation of substrate by Rapidfire mass spectrometric analysis	ic50	0.0631	uM
3-(thiophen-3-ylmethylamino)pyridine-4-carboxylic acid	1282647: Inhibition of KDM4C (unknown origin) using H3K9Me3 peptide as substrate assessed as demethylation of substrate by Rapidfire mass spectrometric analysis	ic50	0.0631	uM
2-[2-hydroxy-5-[(5-methyl-1,2-oxazole-3-carbonyl)amino]phenyl]pyridine-4-carboxylic acid	1282304: Inhibition of N-terminal His6-tagged KDM4C (1 to 352 residues) (unknown origin) expressed in Escherichia coli Rosetta 2(DE3)pLysS using biotinylated histone H3 (1 to 21 residues) lysine 9 trimethylated peptide/2 uM alpha-ketoglutarate as substrate/cofactor measured after 45 mins by TR-FRET assay	ic50	0.0650	uM
(3S,9R,12S,15S,18S,21R,24S,27S,30S,33S,36S,39S)-18,33-bis[(2S)-butan-2-yl]-15,27,30,36-tetrakis(3-carbamimidamidopropyl)-24-(hydroxymethyl)-3-[(4-hydroxyphenyl)methyl]-12-(1H-indol-3-ylmethyl)-10,21-dimethyl-2,5,11,14,17,20,23,26,29,32,35,38-dodecaoxo-7-thia-1,4,10,13,16,19,22,25,28,31,34,37-dodecazabicyclo[37.3.0]dotetracontane-9-carboxamide	1374014: Inhibition of KDM4C (unknown origin) expressed in Escherichia coli using biotinylated peptide as substrate pretreated for 15 mins followed by substrate addition by Alphascreen assay	ic50	0.0650	uM
2-[5-[(4-methoxyphenyl)methoxy]pyrazol-1-yl]pyridine-4-carboxylic acid	1391729: Inhibition of KDM4C (unknown origin) preincubated with enzyme	ic50	0.0680	uM
2-[2-hydroxy-5-[[2-(4-methoxyphenyl)acetyl]amino]phenyl]pyridine-4-carboxylic acid	1282304: Inhibition of N-terminal His6-tagged KDM4C (1 to 352 residues) (unknown origin) expressed in Escherichia coli Rosetta 2(DE3)pLysS using biotinylated histone H3 (1 to 21 residues) lysine 9 trimethylated peptide/2 uM alpha-ketoglutarate as substrate/cofactor measured after 45 mins by TR-FRET assay	ic50	0.0690	uM
2-[4-[[4-[(1S,2R)-2-aminocyclopropyl]phenyl]carbamoyl]-2-pyridinyl]pyridine-4-carboxylic acid;2,2,2-trifluoroacetic acid	1066184: Inhibition of recombinant JMJD2C (unknown origin) incubated for 15 mins prior to substrate addition by AlphaScreen method	ic50	0.0700	uM
2-[5-[(4-chloro-2-phenylmethoxyphenyl)methoxy]pyrazol-1-yl]pyridine-4-carboxylic acid	1391729: Inhibition of KDM4C (unknown origin) preincubated with enzyme	ic50	0.0740	uM
2-[5-[(4-chloro-2-ethoxyphenyl)methoxy]pyrazol-1-yl]pyridine-4-carboxylic acid	1391729: Inhibition of KDM4C (unknown origin) preincubated with enzyme	ic50	0.0780	uM
3-(furan-2-ylmethylamino)pyridine-4-carboxylic acid	1885264: Inhibition of KDM4C (unknown origin) measured by RapidFire mass spectrometry (RFMS)	ic50	0.0790	uM
3-[(3-methylthiophen-2-yl)methylamino]pyridine-4-carboxylic acid	1282647: Inhibition of KDM4C (unknown origin) using H3K9Me3 peptide as substrate assessed as demethylation of substrate by Rapidfire mass spectrometric analysis	ic50	0.0794	uM
3-(4-fluorophenyl)-1,6-dimethylpyrimido[5,4-e][1,2,4]triazine-5,7-dione	1650355: Inhibition of KDM4C (unknown origin) using methylated H3 peptide as substrate by chemiluminescence assay	ic50	0.0810	uM
3-[(4-methylthiophen-2-yl)methylamino]pyridine-4-carboxylic acid	1282647: Inhibition of KDM4C (unknown origin) using H3K9Me3 peptide as substrate assessed as demethylation of substrate by Rapidfire mass spectrometric analysis	ic50	0.1000	uM
3-(1,3-thiazol-4-ylmethylamino)pyridine-4-carboxylic acid	1282647: Inhibition of KDM4C (unknown origin) using H3K9Me3 peptide as substrate assessed as demethylation of substrate by Rapidfire mass spectrometric analysis	ic50	0.1000	uM
2-[[4-chloro-3-(cyclopropylmethoxy)phenyl]methoxy]-1H-pyrrolo[3,2-b]pyridine-7-carboxylic acid	1289412: Inhibition of recombinant human N-terminal GST-tagged KDM4C (2 to 372 residues) expressed in baculovirus infected sf9 cells using biotin-H3K9me3 substrate incubated for 30 mins by TR-FRET assay	ic50	0.1000	uM
2-[(4-chloro-3-methoxyphenyl)methoxy]-1H-pyrrolo[3,2-b]pyridine-7-carboxylic acid	1289412: Inhibition of recombinant human N-terminal GST-tagged KDM4C (2 to 372 residues) expressed in baculovirus infected sf9 cells using biotin-H3K9me3 substrate incubated for 30 mins by TR-FRET assay	ic50	0.1000	uM

CTD chemical–gene interactions

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

Chemical	Actions (top 5)	PubMed papers
Benzo(a)pyrene	affects methylation, decreases expression	8
Valproic Acid	affects cotreatment, increases expression, affects expression	6
Cisplatin	affects cotreatment, decreases expression	3
sodium arsenite	decreases expression, increases expression	2
Phenylmercuric Acetate	affects cotreatment, increases expression	2
Aflatoxin B1	affects expression, decreases expression	2
aristolochic acid I	decreases expression	1
triphenyl phosphate	affects expression	1
alpha-pinene	affects cotreatment, increases oxidation, increases abundance	1
bisphenol A	affects methylation	1
trichostatin A	increases expression	1
butyraldehyde	decreases expression	1
potassium chromate(VI)	decreases expression, affects cotreatment	1
1,2-diaminobenzene	affects response to substance	1
methacrylaldehyde	affects cotreatment, increases oxidation, increases abundance	1
testosterone-3-carboxymethyloxime-bovine serum albumin conjugate	affects expression	1
epigallocatechin gallate	affects cotreatment, decreases expression	1
pentanal	decreases expression	1
4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide	affects cotreatment, increases expression	1
belinostat	increases expression	1
abrine	increases expression	1
dorsomorphin	increases expression, affects cotreatment	1
jinfukang	affects cotreatment, decreases expression	1
(+)-JQ1 compound	increases expression	1
PCI 5002	affects cotreatment, increases expression	1
Resveratrol	affects cotreatment, increases expression	1
Sunitinib	increases expression	1
Acetaminophen	decreases expression	1
Acrolein	affects cotreatment, increases oxidation, increases abundance	1
Air Pollutants	affects cotreatment, increases abundance, increases oxidation	1

ChEMBL screening assays

122 unique, capped per target: 120 binding, 2 functional

Representative assays (with source publication via chembl_document):

Assay ID	Type	Description	Source paper
CHEMBL1054733	Binding	Inhibition of JMJD2C-mediated H3K36 demethylation in human 293T cells at 100 mM	Synthesis and activity of N-oxalylglycine and its derivatives as Jumonji C-domain-containing histone lysine demethylase inhibitors. — Bioorg Med Chem Lett
CHEMBL1738633	Functional	PUBCHEM_BIOASSAY: GASC-1 histone demethylase dose retest Measured in Cell-Free Homogeneous System Using Plate Reader - 2043-01_Inhibitor_Dose_CherryPick_Activity. (Class of assay: confirmatory) [Related pubchem assays (depositor defined):AI	PubChem BioAssay data set

Cellosaurus cell lines

5 cell lines: 3 embryonic stem cell, 2 cancer cell line

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

Cellosaurus	Name	Category	Sex
CVCL_A3L9	SEES3-1V human KDM4C, clone1	Embryonic stem cell	Male
CVCL_A3M0	SEES3-1V human KDM4C, clone2	Embryonic stem cell	Male
CVCL_A3M1	SEES3-1V human KDM4C, clone3	Embryonic stem cell	Male
CVCL_C0BQ	Abcam U2OS KDM4C KO	Cancer cell line	Female
CVCL_SU32	HAP1 KDM4C (-)	Cancer cell line	Male

Clinical trials (associated diseases)

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

Trial	Phase	Status	Title
NCT04134572	Not specified	RECRUITING	Registry of Ollier Disease and Maffucci Syndrome
NCT04844697	Not specified	COMPLETED	Resilience and Coping in a Rare Skeletal Disease Population to Face Coronavirus (COVID-19) Outbreak Distress: a Longitudinal Study
NCT06397443	Not specified	COMPLETED	Ready to Sail: Evaluating Sailing’s Feasibility as Ergotherapy
NCT06749366	Not specified	RECRUITING	Uncovering Genes Behind Cartilage Tumors and Vascular Anomalies Using Genomic Sequencing
NCT07379008	Not specified	COMPLETED	Safety and Efficacy of Non-Setting Paste in Bone Defect Reconstruction